Investigation of statistical decision rules for sequential hematologic laboratory tests.

A statistical data processing program for identifying patients who are likely to have abnormalities on various hematologic laboratory tests is described. The prediction of abnormal levels of serum vitamin B12, serum folate, transferrin saturation, and reticulocyte counts is based on a statistical analysis of the patient's age, sex, and routine blood cell measurements. The program was developed using data from normal-value studies and data from patients who had these laboratory abnormalities. The sensitivity and specificity of the program were evaluated in a controlled prospective study of about 5,000 ambulatory adult patients. The program's predictions also were compared with the laboratory tests requested by the patients' attending physicians. The program was most sensitive for predicting low serum vitamin B12 (74%) and low transferrin saturation (78%). In the prospective evaluation, the predictive values varied from 11% for predicting low serum folate to 65% for predicting low transferrin saturation.


The analytic basis for the use of platelet estimates from peripheral blood smears. Laboratory and clinical applications.

Estimation of the platelet count from examination of peripheral blood smears is a widely practiced procedure, but statistical validity to judge the accuracy of the technic has been lacking. More than 400 patients' platelet estimates and counts were analyzed to develop a simple working formula to permit a reasonably accurate platelet estimate. Smear-to-smear and technician-to-technician variabilities were defined, and the influences of different microscopes on the platelet estimates were demonstrated. Platelet estimates can be used as a rapid, convenient measurement suitable for providing useful information for clinical judgement of a patient's platelet status providing that the method's limitations are recognized.


Manual micromethods for bilirubin determination in sera of adults and children and investigation of reasons for observed differences.

This study compared three micromanual methods for determining bilirubin concentration. The two microchemical methods for total bilirubin, a Jendrassik-Grof procedure and a Unopette procedure, using dimethyl sulfoxide as an accelerator and protein solubilizer, gave comparable results in sera of adults and children. A microspectrophotometric method and the microchemical methods for total bilirubin gave similar results in plasmas of newborns with physiologic hyperbilirubinemia and in sera of older children with no hepatic abnormality. However, the microspectrophotometric method gave higher values in normal and hyperbilirubinemic adult sera. The results obtained with the Jendrassik-Grof and Unopette microchemical methods for direct bilirubin in sera of adults and children showed the values determined by the Unopette to be higher. Using the presently accepted normal range, this difference is significant enough to preclude recommendation of the use of the Unopette method for distinguishing normal from elevated levels of direct bilirubin. Direct bilirubin in newborn serum measured by the Unopette method is considerably higher than that measured by the Jendrassik-Grof method. An investigation to determine the reason for the difference in the direct bilirubin results indicated that the Unopette direct method measures diconjugated bilirubin in amounts similar to those measured by the Jendrassik-Grof method but significantly more monoconjugated bilirubin than the Jendrassik-Grof method.


Multivariate estimation of reference ranges.

This paper describes a new method for estimating reference ranges of 21 frequently performed laboratory tests utilizing routine test results of selected hospital patients. Computer programs perform the selection of patient records and the statistical analysis. The patient selection criteria of (1) short hospital stay and (2) short laboratory record provide a data base rich in normal results. The statistical program excludes records with excessive variation, and in repeated data-exclusion passes through the data base progressively narrows the range of acceptability. The decision to exclude a record is based on the "pooled variation." The average value of the "pooled variation" increases as the range is narrowed. This approach insures that the process stops after a few passes, and the most consistent data remain included in the calculation of reference ranges. Statistical properties of the data sets, as well as comparison with normal ranges for healthy subjects and review of 560 clinical charts, support the idea that serviceable reference ranges are obtained. The method is suitable for monitoring the reference ranges of the laboratory at frequent intervals.


Effects of sodium azide on the quantitation of the chemical constituents of serum. Inhibition of bilirubin and cholesterol.

Azide salts frequently are added as a preservative to biologic fluids and reagents, or are introduced into serum through accidental exposure, intoxication, or pharmaceuticals. Sodium azide can interfere with the quantitation of biochemical constituents in serum. Serum pools containing 0.2-9.0 mg/dl (3.42-153.9 mumol/l) total bilirubin, 0.2-5.0 mg/dl (3.42-94.1 mumol/l) direct bilirubin, and 175-313 mg/dl (4.55-8.14 mmol/l) cholesterol were analyzed using the SMA 12/60. Sodium azide was added in concentrations of 0.1-1.0% (13.6-136 mmol/l). Sodium azide in concentrations of 0.1% (13.6 mmol/l) or more reduced total and direct bilirubin values 60-100%. At concentrations above 0.5% (68 mmol/l), no bilirubin, or only a very small quantity, was measured. Sodium azide at concentrations above 0.05% (6.8 mmol/l) exerted a significant decreasing effect on serum cholesterol values. At 0.1% (13.6 mmol/l) or more, reductions in cholesterol values ranging from 30 to 85% were observed. These studies showed that sodium azide (0.1%, 13.6 mmol/l, or more) in the serum can result in falsely low bilirubin or cholesterol values.


Susceptibilities of Pseudomonas species to tetracycline, minocycline, gentamicin, and tobramycin.

Members of the genus Pseudomonas are widely implicated in human disease. Although most isolates are P. aeruginosa, there have been serious outbreaks of infection with other members of the genus. The susceptibility patterns of 5) Pseudomonas isolates are reported. It was notable that of the four antibiotics tested, uniform susceptibility was observed with minocycline.


Hydrogen sulfide-producing Citrobacter diversus. A re-emphasis of the potential ability of all Enterobacteriaceae to manifest this quality.

Among 68 strains of Citrobacter diversus isolated in a community hospital in a year and a half, six were characterized by late H2S production in iron-agar slants, while otherwise typical. Although not recorded in standard tabulations, the potential for Enterobacteriaciae to develop this quality by plasmid transfer appears to be virtually unlimited, and dictates caution in the use of failure to produce H2S as a criterion for exclusion. In the present group, the use of the adonitol reaction as a means of distinguishing these organisms from more typical H2S producers is emphasized.


The histopathology of mammographic patterns.

No significant correlation between the types of histologic alteration and various mammographic densities as described by Wolfe was found in specimen mammograms from 50 patients with cancer of the breast and a similar number with fibrocystic disease except for a greater incidence of fibrous mazoplasia in the "highest-risk" densities designated DY. This information is inconsistent with prevailing views that relate such risk for the development of mammary cancer to proliferative fibrocystic disease, vis-à-vis epithelial rather than stromal proliferation. This observation does not necessarily mitigate claims of risk attendant with various mammographic patterns, but indicates the need for further evaluation of this stromal alteration as a discriminant in this regard.


Histogenesis of dermatofibrosarcoma protuberans. An ultrastructural study.

Ultrastructural study of five typical lesions of dermatofibrosarcoma protuberans revealed that the basic cell is fusiform and has a somewhat indented nucleus and an even distribution of cytoplasmic organelles. Fragments of basal lamina, intercellular junctions, abundant intercellular fibers, and a tendency to form cellular sheaths also were found. The tumor cells had a strong resemblance to pericytes and perineural cells, as well as marked ultrastructural similarities to neurofibroma. The authors conclude that dermatofibrosarcoma protuberans arises from a primitive fibroblastic cell with a "sheath forming cell" differentiation that has a closer relationship to the perineural cell than to the pericyte.


Scleromyxedema myopathy. Histochemical and electron microscopic observations.

A biopsy-proven case of scleromyxedema (papular mucinosis) with IgG lambda light chain paraproteinemia, eosinophilia and severe proximal myopathy is presented. Muscle biopsy revealed an atypical necrotizing vacuolar myopathy. Histochemical studies of cryostat sections revealed fiber necrosis, severe type II fiber atrophy, and fiber vacuolization with NADH tetrazolium reductase hyperactivity. Electron microscopy showed myocytolysis, reduplication of the basement membrane, and unit membrane-lined vacuoles negative for acid mucopolysaccharide.


Leiomyomatosis peritonealis disseminata. An ultrastructural study.

Electron microscopic features of the eighth documented case of leiomyomatosis peritonealis disseminata identify the main proliferative cell type as a mature leiomyocyte with all its associated ultrastructural features. The histogenesis of this neoplasm is considered to be a multicentric metaplastic change determined by an abnormal tissue response to the elevated hormonal levels occurring in pregnancy or ovarian functioning tumors. It is suggested that the cell of origin is the multipotent subcelomic mesenchymal cell, which retains the capacity to differentiate into several tissues, among them smooth muscle. To illustrate this possibility, myofibroblasts, cells with hybrid characters of fibroblasts and leiomyocytes, were observed; these may represent a transitional stage between the mesenchymal cell and the smooth muscle proliferating cell.


Peritoneal mesothelioma in a male pseudohermaphrodite with asymmetrical gonadal differentiation.

A diffuse peritoneal mesothelioma occurring in a patient with male pseudohermaphroditism and asymmetrical gonadal differentiation (mixed gonadal dysgenesis) is described. Malignancies of mesodermal origin, usually derivatives of the urogenital ridge, appear to occur with increased frequency in male pseudohermaphrodites. This appears to be the first reported instance of a mesothelioma in a male pseudohermaphrodite with mixed gonadal dysgenesis. The clinical and pathologic features of this tumor, including the electron microscopic findings, are presented.


Localized lymphadenitis due to leishmania simulating toxoplasmosis. Value of electron microscopy for differentiation.

Two cases of cervical adenopathy are described. One manifested as lymphoma clinically. Both patients were found to have primary lymph node leishmaniasis without cutaneous, mucosal or visceral involvement. The histologic appearance simulated toxoplasma lymphadenitis. Electron microscopic study differentiated the organism from Toxoplasma, and the condition responded well to antimony therapy.


Peripheral lymphadenopathy in childhood. Ten-year experience with excisional biopsy.

We reviewed our experience with excisional lymph node biopsy over a ten-year period in an attempt to determine which clinical features, if any, were predictive of histologic diagnosis. A total of 75 patients, aged 8 months to 17 years, were available for review. Of these patients, 41 (55%) had nodes with nondiagnostic hyperplasia, 16 (21%) had noncaseating granulomatous lymphadenitis, 5 (7%) showed the caseating lesion of tuberculosis, while 13 (17%) showed a lymphoreticular malignant neoplasm. While patients with lymphoma more frequently had a history of weight loss or arthralgia, no one clinical feature, by either its presence or absence, could predict the biopsy diagnosis. All five patients with supraclavicular lymhadenopathy were found to have mediastinal disease. Of the 41 patients initially found to have nondiagnostic reactive hyperplasia, seven (17%) ultimately proved to have a specific pathologic process.


Narcotic addiction, pregnancy, and the newborn.

Between 1954 and 1973, 101 heroin-addicted mothers gave birth to 149 babies at Vancouver General Hospital. Thirty-seven percent of the infants had low birth weights and two thirds were born preterm. Average birth weight was 2,710 gm as compared with an overall average of 3,420 gm for this hospital. Tobacco and alcohol abuse, and poor maternal nutrition probably contributed to the growth retardation. Withdrawal symptoms were observed in 68% of the babies, and this may have been aggravated by multiple drug use, which was prevalent, including alcohol, barbiturates, and "soft drugs." Neonatal mortality rate of 6.7% and a stillbirth rate of 4% resulted in a perinatal mortality rate of 10.7%. Prematurity, respiratory distress syndrome, and other perinatal complications related to an unfavorable social background accounted for most neonatal deaths, but none was attributable directly to narcotic withdrawal.


The nephrotic syndrome and renal vein thrombosis.

In recent years, there has been a shift away from the concept that renal vein thrombosis is a cause of the nephrotic syndrome. A careful analysis of this subject favors the opposite contention that nephrotic syndrome is a cause of renal vein thrombosis when these two conditions occur in the same patient.


The changing epidemiology of pertussis in young infants. The role of adults as reservoirs of infection.

We reviewed 400 bacteriologically confirmed cases of pertussis in infants and children during the past 18 years. Several changes in the epidemiology have occurred in the most recent six-year period. The incidence of whooping cough in children has decreased by at least 50%, but the proportion of cases occurring in infants younger than 12 weeks of age has doubled to 30% of all cases. Formerly most young infants acquired their illness from siblings or other children, but in the recent period adults in the household were the most common source of infection to neonates and young infants. This observation plus the increasingly high level of immunization in preschool and school-aged children suggest that young adults with waning immunity and mild illness are a major reservoir for transmission of pertussis to infants too young to be immunized.


T3 thyrotoxicosis in a child.

We report the case of a 5-year-old hyperthyroid boy with normal serum T4 levels are elevated serum T3 levels. The findings are diagnostic of T3 thyrotoxicosis, a condition that has been very infrequently reported in childhood. We postulate that low dietary iodine intake may be an etiologic factor in some cases of T3 thyrotoxicosis.


Gray scale ultrasonography in the evaluation of hydrocephalus and associated abnormalities in infants.

Improved gray scale ultrasonic equipment has made two-dimensional echoencephalography a useful diagnostic tool in the examination of the infant brain for fluid-containing structures such as dilated ventricles and cysts. Eighteen infants have been examined to exclude hydrocephalus and other abnormalities. Ten had significantly dilated lateral ventricles and three of these were shown to have associated intracerebral abnormalities. Another infant was demonstrated to have an arachnoid cyst or subdural hygroma with normal size ventricles. Ten of the 11 abnormalities were confirmed by some other neuroradiologic study.


Sensory neuropathy with onion-bulb formation. Report of a case with onset in infancy.

A 27-month-old girl suffered from severe sensory neuropathy with minimal motor dysfunction. The CSF protein level was increased and nerve conduction was severely impaired. Sural nerve biopsy specimen showed increased endoneurial connective tissue. An onion-bulb pattern with concentric interdigitations of Schwann cell cytoplasmic processes and redunbant basal laminae were prominent features under electron microscopy. Degress of myelination in individual fiber was far less than expected. Although the clinical manifestations of onion-bulb neuropathy with onset in infancy have been reported to resemble infantile progressive spinal muscular atrophy, the present case demonstrates that the condition can also appear as severe sensory ataxia.


Dyssegmental dwarfism. A lethal anisospondylic camptomicromelic dwarfism.

Dyssegment dwarfism is a lethal anisospondylic camptomicromelic form of growth retardation that appears to have autosomal recessive inheritance. It is characterized by short neck, cleft palate, narrow chest, severe shortening of long bones and trunk, reduced joint mobility, inguinal hernia, and probably hirsutism and hydroureter/hydronephrosis. Some cases are seen with occipital exencephalocele. The long bones are short and bent with metaphyseal flaring. The vertebral bodies are of different size and many consist of separate ossified masses. The iliac bones are small with hypoplasia of the horizontal and inferior margina. Maturation of cartilage cells at the epiphyseal plates is grossly disturbed and there are puddle-like spaces among the resting cartilage cells.


The Coffin-Siris syndrome.

We present the sixth reported case of the Coffin-Siris syndrome. This disorder is characterized by the absence of the nails of the fifth fingers and toes, severe mental and developmental retardation, and postnatal growth deficiency. Feeding and respiratory problems are prominent features. The Dandy-Walker malformation was found at autopsy in our patient. This malformation was also present in the only other patient with this syndrome whose autopsy has been reported.


Leukocyte counts in children with sickle cell disease. Comparative values in the steady state, vaso-occlusive crisis, and bacterial infection.

Total and differential WBC counts were measured in 88 children with sickle cell hemoglobinopathies during the steady state, vaso-occlusive crisis, and bacterial infection. Steady state leukocyte values were lower than anticipated on the basis of currently available information. Total and segmented leukocyte numbers were greatly increased during vaso-occlusive crisis and infection, but only with bacterial infection was there a consistent increase in bands or nonsegmented leukocytes (mean, 4,580/microliter). On the basis of these data we believe that total and differential leukocyte counts are of value for identifying those children with potentially serious bacterial infections.


Inappropriate antidiuretic hormone secretion in premature infants with cerebral injury.

We describe 11 premature infants with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The syndrome is far more common than the single case report in the literature would indicate. All the infants had either asphyxiation at birth, intracranial hemorrhage, or meningitis. Of the nine children available for follow-up observation, seven demonstrated serious neurological sequelae. The diagnosis of SIADH in the premature neonate may be difficult to establish due to the complexity of precipitating factors.


Behavioral treatment of obesity in children.

The development of behavioral techniques for the control of obesity in children is reviewed. Techniques developed for the treatment of obese adults have recently been modified for use with children, and to date, six studies exist that have evaluated their use. The results are encouraging and it appears that behavior therapy offers new promise in the treatment of this difficult problem. The review ends with a survey of behavioral techniques and suggestions for further reading.


Clinical estimation of liver span in infants and children.

The liver span in 350 infants and children was determined by percussion of the upper and lower borders in the midclavicular line. Mean liver span was found to be related to age curvilinearly and ranged from a minimum of 1.9 cm at 1 week of age to a maximum of 7.7 cm in males and 6.3 cm in females at 20 years of age. In children with normal growth patterns, age and sex were found to be the major factors influencing liver size. Though height and weight also correlated with liver span, these variables did not add substantially to the correlation using age and sex alone. The presence of minor systemic illnesses, eg, otitis and gastroenteritis, did not affect liver span. The expected normal values for liver span at different ages for male and female children have been established and provide the basis for comparison during routine physical examination.


Intraventricular and parenteral gentamicin therapy for ventriculitis in children.

Five children with intraventricular shunts developed ventriculitis due to organisms resistant to multiple antimicrobial agents but sensitive to gentamicin sulfate. No gentamicin was detected in ventricular CSF of four patients at a time when gentamicin was being administered only intravenously. The intraventricular administration of 1 mg of gentamicin resulted in ventricular CSF concentrations greater than 20 microgram/ml one hour and 5 to 14 microgram/ml 36 hours after administration. Patients were treated with intraventricularly given gentamicin for an average of 16 days, with no apparent complications or relapses during the 12- to 24-month follow-up period. Intraventricularly administered gentamicin sulfate (1 mg every 24 to 36 hours) in conjunction with complete shunt removal was an effective means of therapy of ventriculitis caused by bacteria resistant to antibiotics that readily penetrate the blood-brain barrier.


Distichiasis complicating allergic rhinoconjunctivitis.

Three patients had four lid distichiasis and signs and symptoms of allergic rhinoconjunctivitis. The findings consisted of ocular irritation with tearing, photophobia, periodic lid swelling, rhinorrhea, and boggy nasal mucosa. Treatment of the allergic rhinoconjunctivitis was unsuccessful until the distichiasis was relieved. Exacerbations of signs and symptoms recurred when lashes regrew. A neural reflex relationship exists to explain most of the symptom complex resulting from ocular irritation. In the evaluation of patients with rhinoconjunctivitis, trichiasis should be looked for, especially if there is noticeable photophobia present.


The diagnosis of Leydig cell tumors in childhood.

We report the clinical and hormonal findings in two boys with isosexual precocity secondary to Levdig cell tumor of the testis. The hormonal profile at the initial evaluation was quite different in the two cases suggesting differences in steroid biosynthesis by the tumors. These differences indicate that a dexamethasone suppression test may be required to differentiate between Leydig cell tumors and congenital virilizing adrenal hyperplasia with adrenal rest tissue located within the testes.


Inherited partial trisomy 8q (22 leads to qter).

We report clinical observations and cytogenetic studies of an inherited form of partial trisomy 8q. Although complete trisomy 8 has in recent years proven to be a clinically recognizable syndrome, partial trisomy 8q has been documented in only six individuals. Of these, five were familial and also partially trisomic for chromosome 22. There has been only one prior report of partial trisomy 8q without partial trisomy 22. Review of these cases provides support for the recent suggestion that the phenotype of trisomy 8 may be caused principally by trisomy of the distal segment of 8q.


Giant hyperplastic polyp of the colon simulating adenocarcinoma.

Hyperplastic polyps of the colon have been previously reported as frequent incidental asymptomatic lesions limited to 1 cm. in size. To our knowledge, this is the first recorded case of a hyperplastic polyp of such magnitude as to cause obstructive symptoms and clinically simulate adenocarcinoma of the colon.


The coordination of gastrointestinal hormones and the autonomic nerves.

We have conducted investigations on the relationship between gastrointestinal hormones and the autonomic nervous system. In this paper are described main themes of our investigations where a close association between gastrointestinal hormones and the autonomic nervous system was shown from the functional and morphological points of view. The "nervism" proposed by Pavlov, where the regulation of various organs in the body was thought to be accomplished wholly by the nervous system, was based on the findings on the physiology of the digestive glands. In the meantime, the discovery of secretin from the duodenal mucosa led Bayliss and Starling to propose a chemical co-ordination or a humoral regulatory mechanism in addition to the nervous system for the regulation of the various organs in the body. It is indeed surprising that the principle of two major regulatory mechanisms in the body was thus developed originally on the basic studies of the exocrine and endocrine function of the digestive system. Our investigations reported in this paper disclosed the fact that the neural and humoral regulatory mechanisms for gastrointestinal secretions acted not separately but in close association both morphologically and functionally.


Immunological studies in chronic atrophic gastritis and chronic (superficial) gastritis.

Detection of autoantibodies, HLA typing and immunofluorescence studies on gastric biopsies were carried out in subjects with histologically proven chronic atrophic gastritis (CAG) and chronic superficial gastritis (CG). All were seronegative for parietal cell antibody and did not have pernicious anemia. Except for positive antismooth muscle and antimitochrondrial antibodies in one patient with CAG, autoantibodies (antinuclear, smooth muscle, mitochrondrial, parietal cell) were absent in patients with CAG and CG. Immunofluorescence studies showed that Ig-G and IgA were presented in the lamina propria of all cases with CAG or CG and of subjects with normal gastric histology. Ig-M was seen less often, in about half the cases. Complement C3 was an uncommon finding, being positive in only one case with CAG and one case with CG and in none of the cases with normal gastric histology. Fibrinogen was more commonly seen in patients with CG (5/5 cases) than in those with CAG (3/11 cases). Fibrinogen was found in one case with normal gastric histology. The most consistent fluorescence was obtained with antiparietal cell antiserum. All subjects with CAG showed negative or weak staining only. In contrast, subjects with CG and normal gastric histology had strong specific fluorescence. An increased frequency of HLA-A1 plus HLA-B8 was found in subjects with CAG (20.7% in controls; 40% in CAG).


Enteric fever: a clinicopathologic study of 104 cases.

The records of 104 patients with culture-proven enteric fever were reviewed and evaluated as to the clinical signs, laboratory findings, pathologic features and complications of the disease. One patient with fatal disseminated intravascular coagulation and enteric fever is also presented. Fever and bradycardia were the leading clinical signs followed by splenomegaly, hepatomegaly and rose spots. The principal complications of enteric fever included anemia, typhoid hepatitis, relapse and bleeding. Evidence of typhoid hepatitis was present in 30% of the patients tested. The pathology consisted of typhoid nodules of variable frequency and size depending upon the severity of the condition. The relationship of typhoid hepatitis to relapse seems to be more than coincidental as four out of seven patients who had relapse had abnormal liver tests. The occurrence of disseminated intravascular coagulation in enteric fever is rare; however, awareness of such a potential complication may be life-saving to the patient.


Tolazamide-induced hepatic dysfunction.

A case of tolazamide-induced hepatic injury is reported. Injury was documented by abnormal liver tests, including an elevated alkaline phosphatase, 5' nucleotidase and serum glutamic oxaloacetic transaminase. Liver biopsy confirmed the degree and type of injury which consisted of severe portal inflammation, bile duct proliferation and early fibrosis. The case is reported to further establish tolazamide as a drug capable of producing hepatic injury and to report a new form of hepatic injury attributable to a sulfonylurea agent.


Pancreatic pseudocyst presenting as massive hemothorax: a case report.

The case of a 36-year old man who presented with massive recurrent hemothorax as a complication of a pancreatic pseudocyst is described. Some of the complications of pancreatitis and pancreatic pseudocysts are discussed. Recurrent hemothorax represents an unusual pulmonary complication of pancreatic pseudocysts to be included in the differential diagnosis of pleural fluid collections in pancreatitis.


Peritoneal lavage in the treatment of acute pancreatic ascites.

A case of intraperitoneal rupture of a pseudocyst associated with ascites is presented. Peritoneal lavage was successful in the initial management and allowed definitive surgery to be performed at a more opportune time. When faced with a case of intraperitoneal rupture of a pseudocyst, peritoneal lavage should be considered as an alternative to emergency surgery.


Gastric outlet obstruction due to a pancreatic pseudocyst: report of two cases.

Two cases of gastric outlet obstruction, secondary to a pseudocyst of the pancreas, are described. The striking radiologic pictures are shown. The pathogenesis of this complication is discussed and a greater awareness of this entity is stressed.


Patent ductus arteriosus and ventricular septal defect: trends in reported frequency.

Nationwide secular increases in the reported frequency of patent ductus arteriosus (PDA) and ventricular septal defect (VSD) are presented. Detailed examination of data from one locality, Metropolitan Atlanta, indicates that the increases were primarily the result of a rise in the reported frequency of these heart defects in isolated form (i.e., without other malformations). During the latter years of the study more Atlanta babies with isolated PDA were of low birth weight and short gestational age, and more cases were diagnosed in the infants' first week of life. The increase in VSD was not as consistent nor as dramatic as that of PDA. Neither were there any changes over time in the demographic characteristics of Atlanta infants affected by isolated VSD. At least part and perhaps all of the increase in PDA may be explained by an increased awareness on the part of physicians who take care of premature infants. While the increase in reported VSD may be explainable on the basis of awareness or secular shifts in diagnostic standards, the problem seems qualitatively different from that of PDA.


Induced abortion and spontaneous abortion: no connection?

The hypothesis that spontaneous abortion is associated with prior induced abortion is tested in an epidemiologic study. The reproductive histories of a consecutive series of women admitted to hospital with spontaneous abortions were compared with those of a control series of women who delivered after 28 weeks gestation. There is no association between spontaneous abortion and prior induced abortion. The power of the analysis to detect a 30% excess in the frequency of induced abortion in cases as compared to controls is 82% at alpha = .05. The design and analysis effectually controlled for all potentially confounding factors.


The epidemiology of respiratory distress syndrome in Norway.

Information collected through the Medical Birth Registry of Norway on a seven-year cohort of 457,465 live births for the years 1967--73 were used to determine the factors associated with the risk of respiratory distress syndrome (RDS). A total of 1235 cases were identified and 510 of these died, resulting in an incidence rate of 2.7 and a mortality rate of 1.1 per 1000 live births. From a geographic breakdown of counties there was no association of the incidence or mortality of RDS with such environmental factors as latitude, longitude, urbanization, industrialization or level of obstetric care. There was an increase in reported incidence and mortality over time, and a slight peak during fall months. The major factors associated with the risk of RDS in Norway were birth weight, gestational age, male sex, cesarean sections and some other complications of pregnancy or delivery. When rates were adjusted for birth weight and gestational age there was no association with maternal age, parity or marital status. Such adjustments reversed the risk of RDS among multiple births to a rate lower than that for single births.


Prostatic cancer: mortality and incidence rates by race and social class.

Among the most striking epidemiologic characteristics of prostatic cancer in the United States is the sizeable excess in rates for the disease among blacks as compared with whites. This study attempted to determine whether the higher black rates might be explained by controlling for social class, using mortality data from Alameda County for the pericensal period 1968--1972 (n = 400), and the population-based series of cases for Alameda County included in the Third National Cancer Survey, 1969--1971 (n = 750). Reviewed first are previous studies addressed to the relationship of prostatic cancer and socioeconomic status (SES), most of which have been confined to whites. In the present study, each death or case was assigned to a socioeconomic class based on census tract of residence and rates by race and social class determined. Comparison of age-specific mortality and incidence rates by SES reveals no gradient for prostatic cancer in either whites or blacks.


Acinetobacter calcoaceticus outbreak associated with peritoneal dialysis.

Investigation of an outbreak of contamination of dialysis drainage fluid with Acinetobacter calcoaceticus var. anitratus identified a previously unrecognized source for dialysis associated infections. Over a 4-month period, 25 peritoneal dialysis treatments were administered to 13 hospital patients. Of the 25 treatments for which culture results were available, 14 were associated with dialysis drainage fluid cultures positive for A. calcoaceticus. A water bath used to warm bottles of peritoneal dialysate before use was the reservoir for the bacteria, and investigation showed in vitro that bath water could contaminate the dialysate. It appears likely that the dialysate became contaminated when the prong of the fluid administration set was inserted through the rubber bung on the dialysate bottles. This outbreak illustrates the potential importance of environmental reservoirs in infections complicating peritoneal dialysis.


An explanation for the high incidence of congenital rubella syndrome in Ryukyu.

An exceptionally high incidence of congenital rubella syndrome (CRS) has been noted in Ryukan children who were infants in utero during an extensive rubella epidemic in the Ryukyu Islands in 1964 through the spring of 1965. In 1965, the Congenital Rubella Study Group of Kyushu University registered in the Ryukyus 408 cases of CRS and an incidence of 20 cases of CRS per 1000 births. The nearby Amami Islands, on the other hand, had a low incidence of CRS. Seroepidemiologic studies indicated a high prevalence of antibodies in the Ryukyus but a low prevalence in the Amamis. Since CRS is uncommon throughout Japan, some investigators have hypothesized that Japanese strains of the virus are avirulent and that a virulent American strain caused the epidemic in the Ryukyus. However, retrospective seroepidemiologic studies reported here indicate that the high incidence of CRS in the Ryukyus was more probably due to low seropositivity and a resultant high attack rate of rubella among pregnant women, rather than to a hypothetical virulent teratogenic strain of rubella virus. Conversely, the data suggest that the low incidence of CRS in Japan may reflect the infrequency of rubella nonimmunes in women of childbearing age.


Macro-monitoring: a step toward rational psychopharmacotherapy.

A 15-item checklist was used to monitor the drug therapy of 516 patients in five clinical settings. The primary purpose of this study was to determine the extent of irrational drug use in these several settings. After gathering baseline data, two similar clinical units were selected for a six-month follow-up to determine the impact of drug consultation by an expert clinical psychopharmacologist. In the unit where drug consultation was provided, there was a significnat reduction in extended antiparkinsonian agent use (p less than 0.001), multiple daily dosage (p less than 0.001), inappropriate anxiolytic use (p less than 0.01), polypharmacy (p less than 0.001) and too rapid change in medication (p less than 0.01). The unit that did not have drug consultation continued to have a high percentage of patients receiving drugs in an inappropriate manner. Although the consultant had a significant impact on drug use, it was recognized that such consultation is not feasible for most psychiatric facilities. The checklist itself is a systematic tool that can be used to identify prescribing practices of questionable appropriateness. If used properly by the pharmacist, the checklist can serve as a supportive system to assist the physician in providing better patient care.


Structural codes and patient safety: does strict compliance make sense?

The authors of this Comment note recent trends rigidifying the enforcement of building and safety codes for health care facilities and compare the estimated costs (in terms of dollars spent) of those trends with their anticipated benefits (in terms of potential years of human life saved). They estimate that for each potential year of life saved, strict enforcement of the Life Safety Code of the National Fire Protection Association would cost $12.7 to $63.5 million for hospitals and $1.1 to $2.6 million for nursing homes, the latter figure based on Massachusett's experience. These figures are contrasted to the cost of routine kidney dialysis, which is generally acknowledged to be an extremely expensive technology, costing approximately $20,000 per potential year of life saved. The authors suggest that even if strict enforcement of the Code were fully effective (which, given the current structure of the Code, seems doubtful), a portion of the substantial financial resources expended from our limited national health care budget in hewing to the letter of the Code might be better spent on other activities with greater potential yield in improving the quality of life for patients in hospitals and nursing homes.


Clinical relevance of the effect of hepatic disease on drug disposition.

The effect of hepatic disease on the metabolism of drugs is reviewed. Drugs discussed include those acting on the central nervous system (phenobarbital, pentobarbital, amobarbital, diazepam, chlordiazepoxide, oxazepam, clorazepate, chlorpromazine, morphine, meperidine, phenytoin); those acting on the cardiopulmonary system (digoxin, digitoxin, lidocaine, theophylline); antineoplastic agents (azathioprine, 6-mercaptopurine, doxorubicin), antimicrobials (carbenicillin, ampicillin, nafcillin, chloramphenicol, clindamycin, lincomycin, rifampin, isoniazid, aminosalicylic acid) and antiinflammatory agents (phenylbutazone, prednisone). The effect of hepatic dysfunction on drug disposition is not consistent or predictable. The efficiency with which drugs are metabolized by the liver, the extent of drug plasma binding, and the etiology and stage of the hepatic disorder are each important in determining whether drug disposition will be altered.


Perceived benefits of the Pharm.D. as a second pharmacy degree.

The perceived benefits of the Pharm.D. as a second degree was studied among pharmacists who earned the degree after the B.S. degree in pharmacy. A questionnaire was mailed to post-B.S. Pharm.D. recipients who graduated after 1968. The 224 pharmacists (72%) who responded represented 54 baccalaurate and 12 Pharm.D. programs. Sixty-seven percent had gained hospital practice experience prior to returning to school for their Pharm.D. degree. The data did not show "job dissatisfaction" to be a major factor prompting pursuit of the Pharm.D. Most initially sought the advanced degree in an attempt to gain greater patient involvement (43%). In 10 years, 51% hope to have attained some kind of administrative position, 15% desire to have combined clinical and administrative responsibilities, while 37% prefer a purely clinical position. Thirty-four percent would like to have a position in education. Most respondents in institutional practice (59.4%) and education (88.6%) felt they would not have their present position without the Pharm.D. degree. Fifty-nine percent receive an annual salary greater than $21,000 including fringe benefits. Most pharmacists who earned a post-B.S. Pharm.D. degree believe they have benefited from their advanced professional degree, both in job responsibilities and salary.


Rapid miniaturized chromatographic quality control procedures for iodinated radiopharmaceuticals.

A rapid, miniaturized chromatographic system was developed to determine the labeling efficiency of iodinated radio-pharmaceuticals including I-131 orthoiodohippurate, I-131 rose bengal, I-125 RISA, and I-131 19-iodocholesterol. The system consists of three specific chromatography strips (Whatman 31ET paper chromatography, silica gel and silicic acid instant thin-layer chromatography) and three solvents (chloroform:glacial acetic acid in a 1.00:0.05 v/v mixture, absolute methanol, and 0.9% sodium chloride). The strips are color-coded, miniaturized, and appropriately labeled. The chromatographic quality control procedures are easy to use, rapid, and can be incorporated easily in a routine quality control program.


The pharmacy clinic: a new approach to ambulatory care.

A pharmacy clinic was established to provide consultation and services to practitioners and patients in the ambulatory care department of a Veterans Administration hospital. Among the services provided by the pharmacist are drug therapy consultations and monitoring, drug use review, drug information, and patient education. The pharmacy clinic assures the staff of the pharmacist's availability for consultation, allows the pharmacist to better organize the time required for consultation, makes the services of the pharmacist available to all outpatients, and provides a good training environment for students.


Errors remaining in unit dose carts after checking by pharmacists versus pharmacy technicians.

The accuracy of pharmacists and pharmacy technicians in checking unit dose carts was compared. One-half of the unit dose patient medication drawers, for a 92-bed medicine service in a 450-bed teaching hospital, were checked by pharmacy technicians and the remaining by pharmacists. These drawers then were checked again to determine the number and type of checking errors committed by technicians and pharmacists. During the 10-day study, carts checked by pharmacists contained over twice as many errors (1.85%) as similar carts checked by technicians (0.87%). The results suggest that pharmacy technicians could probably be trained to perform the cart-checking task in unit dose drug distribution systems. Time-extended studies should be done to determine if technician performance is maintained after the novelty of the task wears off.


Drug information services in an oncology institution.

Information requests received over a 14-month period in the drug information service of an oncology hospital were reviewed. Requests were classified as to the nature of the question, category of requestor and geographical distribution of both questions and requestors. Inquiries were tabulated as either oncology-related or nononcology and further divided into one of 12 information categoreis. Those questions concerning investigational chemotherapy and unproven cancer remedies were tabulated. An average of 104 requests monthly were received. Prescribing practitioners accounted for 47.7% of all inquirers. Overall, 39.4% of total requests were oncology-related. The majority (72%) of total requests originated within the institution. The greatest number of requests (17.7%) were of a general review nature. The second greatest number (14.3%) were efficacy-related questions which solicited an opinion as to the appropriateness of drug use. Methods need to be developed for measuring the impact of drug information services on prescribing habits.


Using pharmacokinetics in drug therapy II: Rapid estimates of dosage regimens and blood levels without knowledge of pharmacokinetic variables.

A modification of the superposition method, which yields fast and reasonably accurate estimates of dosage regimens and steady-state maximum and minimum blood levels, is described. In the modified superposition method, input data are obtained from the blood, plasma or serum concentration vs time profile resulting from administration of a single dose of the drug. These estimates are valid only when the pharmacokinetics of the drugs are linear and elimination from the body occurs according to first-order kinetics. Limitations of the method are discussed. It is concluded that this is a rapid and clinically useful method for pharmacokinetic estimations.


Echocardiographic abnormalities in patients with transfusion-dependent anemia and secondary myocardial iron deposition.

The heart was evaluated by echocardiography in 56 patients at risk for myocardial iron deposition. Fifty-four had congenital anemia for which they required repeated transfusions, and two had primary hemochromatosis. The data, plotted according to one of three functions of the body surface area, were compared to values obtained in 105 normal subjects whose age spanned a similar range. Left ventricular wall thickness, transverse dimension and mass, as well as left atrial transverse dimension, were increased in the majority of patients with chronic iron overload despite the infrequent occurrence of cardiac enlargement on routine chest films (32 per cent) or electrocardiographic abnormality (16 per cent). Left ventricular ejection fraction was normal in all but four patients. These four patients died within a six month follow-up period suggesting that deterioration in systolic function is an indicator of poor prognosis. Our findings indicate that echocardiography provides a simple noninvasive means for assessing changes in cardiac structure and function that should prove useful in the serial evaluation of patients who are at risk for the development of myocardial iron deposition.


Pharyngeal aspiration in normal adults and patients with depressed consciousness.

A sensitive technic using indium111 chloride was devised to investigate the occurrence of pharyngeal aspiration. Twenty normal subjects and 10 patients with depressed consciousness were studied. Forty-five per cent of the normal subjects aspirated during deep sleep. Normal subjects who did not aspirate were noted to sleep poorly. Seventy per cent of the patients with depressed consciousness aspirated. Aspiration of pharyngeal secretions occurs frequently in patients with depressed sensorium and also in normal adults during deep sleep. Bacterial pneumonia may result when aspirated bacteria are not effectively cleared. This may result when clearance mechanisms are impaired or when they are overwhelmed by large volumes of aspirated secretions.


Renal oxalate excretion following oral oxalate loads in patients with ileal disease and with renal and absorptive hypercalciurias. Effect of calcium and magnesium.

Intestinal absorption of oxalate was assessed indirectly from the increase in renal oxalate excretion following the oral administration of 5 mmol of stable oxalate. When sodium oxalate alone was given without divalent cations to patients in the fasting state, the urinary oxalate increased promptly (within 2 hours). The increase was more prominent and sustained in those with ileal disease (ileal resection or jujunoileal bypass); thus, 35 per cent of the orally administered oxalate eventually appeared in the urine in the group with ileal disease, 8 per cent in the group with stones (renal and absorptive hypercalciurias) and 9 per cent in the control group. This hyperexcretion of oxalate could be largely, but not totally, ameliorated by the concurrent oral administration of divalent cations. Although urinary oxalate decreased significantly following the oral administration of calcium or magnesium, hyperoxaluria persisted in most patients. The results suggested that the hyperabsorption of oxalate in ileal disease cannot be accounted for solely by an increased absorbable oxalate pool associated with calcium-fatty acid complexation. Moreover, although urinary oxalate decreased, urinary calcium increased concurrently when either calcium or magnesium was given. Thus, there was no significant change or increase in the urinary state of saturation with respect to calcium oxalate.


Spontaneous bacterial peritonitis. A review of 28 cases with emphasis on improved survival and factors influencing prognosis.

During a five year period, 28 episodes of spontaneous bacterial peritonitis were documented. The number of cases recognized annually increased during the study period. Clinical and laboratory features of spontaneous bacterial peritonitis were similar to those previously reported; however, mortality was considerably lower (57 per cent). Factors associated with adverse prognosis were increasing hepatic encephalopathy, more than 85 per cent granulocytes in peripheral blood or ascitic fluid, total bilirubin greater than 8 mg/dl and serum albumin less than 2.5 g/dl. Temperature greater than 38 degrees C was associated with increased survival. Infection by enteric organisms was associated with higher mortality than infection by nonenteric organisms. Unexpectedly, patients with bacteremia fared no worse than those whose blood remained sterile. The data suggest that in patients with leukocyte counts greater than 1,000 cells/mm3 and more than 85 per cent granulocytes in their ascitic fluid, the likelihood of spontaneous bacterial peritonitis is high. Such patients deserve empiric antibiotic therapy pending the results of appropriate cultures.


The assessment of immunologic and clinical changes occurring during corticosteroid therapy for allergic bronchopulmonary aspergillosis.

Twenty-two patients with allergic bronchopulmonary aspergillosis have been treated and evaluated for a period ranging from two months to nine years. Twelve are available for periodic blood sampling. Data are presented suggesting the following: (1) Patients with allergic bronchopulmonary aspergillosis have high initial levels of total serum immunoglobulin E (IgE). These levels are significantly higher in those patients who had not been previously treated with prednisone for the control of asthma. (2) Treatment with alternate day prednisone (0.5 mg/kg given on alternate days) caused clinical and roentgenologic improvement as well as marked decreases in total serum IgE but does not necessarily prevent recurrence of the disease. (3) Total and specific IgE against Aspergillus antigen may increase prior to and during exacerbations of disease. (4) Specific IgG and IgE against Aspergillus antigen are increased in most patients with allergic bronchopulmonary aspergillosis and reflect disease activity as evidenced by x-ray and clinical exacerbations in some cases. (5) Lymphocyte transformation using Aspergillis antigen, as measured by the whole blood technic, is present in patients with allergic bronchopulmonary aspergillosis, but serial changes in lymphocyte transformation do not correlate with disease activity. (6) Precipitin reactions are present in patients with allergic bronchopulmonary aspergillosis, but presence or absence does not reflect disease activity in most cases.


The role of vasopressin in the impaired water excretion of myxedema.

The plasma vasopressin response to acute water ingestion was evaluated in 20 patients with myxedema prior to definitive treatment and in eight of these same patients following therapy of their hypothyroidism. Vasopressin levels were elevated and failed to completely suppress following water ingestion in 15 subjects (75 per cent). Two hypothyroid patients with elevated plasma vasopressin levels (10 per cent) had a normal renal response to the water challenge suggesting partial end organ hormonal unresponsiveness. In three (15 per cent) of the five patients with suppressible vasopressin, water excretion was impaired indicating a nonvasopressin-mediated renal defect. In eight patients restudied after achievement of a euthyroid state, vasopressin inhibition and urinary excretion were normal following the oral water load. Although intrinsic renal changes in the hypothyroid state may contribute to the observed defect in water diuresis, the present study suggests a role of endogenous vasopressin in this disorder.


Correlation of antistaphylococcal antibody titers with severity of staphylococcal disease.

Counterimmunoelectrophoresis (CIE) was utilized to determine antistaphylococcal precipitin antibody titers in patients with various staphylococcal diseases and in control subjects. Patients with staphylococcal disease comprised five cases of endocarditis, 22 of deep tissue infection (including seven cases of osteomyelitis), six of bacteremia and six of skin infection. Control subjects consisted of 31 patients with nonstaphylococcal bacteremias, 29 hospitalized patients without infection and 30 healthy subjects. Antistaphylococcal antibodies were present in all patients with staphylococcal endocarditis and deep tissue staphylococcal infection, and all but three had titers greater than or equal to 1:4. No significant difference in titers was found between these two groups of patients. Antibodies, although present in some patients in the other categories, were detected less frequently; only two patients had titers greater than or equal to 1:4. Thus, an antistaphylococcal antibody titer by CIE of 1:4 or greater may be an additional diagnostic parameter helpful in distinguishing patients with staphylococcal endocarditis or deep tissue infection from those with other forms of staphylococcal infection and from noninfected subjects.


Relationship between colloid osmotic pressure and pulmonary artery wedge pressure in patients with acute cardiorespiratory failure.

Close relationships between progressive respiratory failure, roentgenographic signs of pulmonary opacification and decreases in the difference between colloid osmotic pressure of plasma and the pulmonary artery wedge pressure (colloid-hydrosatic pressure gradient) were demonstrated in 49 critically ill patients with multisystem failure, in patients in shock. The potential importance of this relationship is underscored by the observation that fatal progression of pulmonary edema was related to a critical reduction in the colloid-hydrostatic pressure gradient to levels of less than 0 mm Hg. More often, reduction in colloid osmotic pressure rather than increases in left ventricular filling pressure (pulmonary artery wedge pressure) accounted for the decline in colloid-hydrostatic pressure gradient. Routine measurement of colloid osmotic pressure, preferably in conjunction with pulmonary artery wedge pressure, is likely to improve understanding of the mechanisms of acute pulmonary edema.


Decrease in circulating immune complexes during hemodialysis.

Raji cell radioimmunoassay and Clq solid phase radioimmunoassay were used to determine serially circulating immune complexes in a patient with rapidly progressive glomerulonephritis who was receiving hemodialysis therapy. Initiation of hemodialysis was associated with a significant decrease in detectable immune complexes which, in turn, was associated with improvement and stabilization of renal function. We suggest that hemodialysis may remove immune complexes from the circulation and that it could be of therapeutic benefit in selected patients with presumed immune complex-mediated glomerulonephritis.


Left atrial myxoma infected with Histoplasma capsulatum.

A patient is presented in whom a left atrial myxoma was found to be infected with Histoplasma capsulatum. Histoplasmosis has not been previously associated with this tumor, nor has any fungus without preceding bacterial endocarditis and long-term antibiotic therapy. The clinical course in foru previously reported cases of bacterially infected myxoma is reviewed. There have been 18 prior cases of Histoplasma endocarditis and in two the patients have survived. Their clinical presentation and response to therapy are also reviewed, and pertinent therapeutic conclusions drawn. The role of echocardiography in this patient's evaluation and the ultimate successful therapy are discussed.


Hemodialysis for methanol intoxication.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.


Serious infections caused by Streptococcus milleri.

Viridans streptococci continue to be the most common etiologic agents in bacterial endocarditis. The spectrum of diseases other than endocarditis caused by these organisms, however, has received sparse attention. Moreover, little clinical information is available concerning the individual viridans streptococcal species. During the 16 months of this study, one species of viridans streptococci, Streptococcus milleri, caused a surprising number of clinically significant suppurative infections. Clinical syndromes included the following: abscesses, 10 cases; peritonitis, four cases; endocarditis, three cases; cholangitis, empyema and cellulitis, one case each. A gastrointestinal source was apparent in eight of these 20 cases. Review of 58 cases of viridans streptococcal endocarditis demonstrated that although Strep. milleri was an infrequent cause of endocarditis, this species was associated with an unusual frequency of suppurative complications. Our experience suggests that Strep. milleri may be more commonly associated with serious suppurative infections than other viridans streptococci and that species identification may be a clinically useful procedure.


Reduction of renal function by newer nonsteroidal anti-inflammatory drugs.

Because aspirin and indomethacin, two structurally dissimilar anti-inflammatory agents which reduce prostaglandin synthesis, both alter renal function, we studied the effect on renal function of three new nonsteroidal anti-inflammatory drugs which also reduce prostaglandin synthesis. We have shown that ibuprofen, naproxen, and fenoprofen are able to reduce renal function in patients with systemic lupus erythematosus and that such changes are associated with reduced excretion of urinary prostaglandin E (PGE)-like compounds. The changes may attenuate despite continued drug administration. These findings emphasize that renal function must be assessed with caution in patients taking these and perhaps other drugs which inhibit prostaglandin synthesis.


Lactobacillemia--report of nine cases. Important clinical and therapeutic considerations.

Serious infections due to lactobacilli have been rarely cited. We report our findings in nine recent patients with lactobacillemia. In the combined literature and current experience, endocarditis and sepsis from localized suppuration were the most common clinical syndromes, most frequently arising from prior oropharyngeal infections. Lactobacillus endocarditis showed a predilection for left-sided cardiac involvement (100 per cent) and systemic arterial embolization (55 per cent). The nine clinical isolates were tested for minimal inhibitory and bactericidal concentrations (MICs and MBCs) against five drugs with broad gram-positive spectrums; of note, these organisms demonstrated a high incidence of both unachievable MBCs (64 per cent) and widely disparate (greater than 100 fold) MIC:MBC ratios (38 per cent). This is in accord with observations in Lactobacillus endocarditis of poor in vivo clinical response despite "appropriate" regimens and achievable MICs of the organisms. Bactericidal synergistic studies on two endocarditis isolates indicated that the penicillins plus aminoglycosides may be potentially useful in the treatment of deep-seated Lactobacillus infections when single antimicrobials fail to achieve a cure.


Monoclonal gammopathy of undetermined significance. Natural history in 241 cases.

Two hundred forty-one patients with a monoclonal protein in the serum but initially no evidence of multiple myeloma, macroglobulinemia, amyloidosis or lymphoma were followed up for more than five years. At the conclusion of the studies the patients were classified as follows: Group 1, patients without significant increase in monoclonal protein, 57 per cent; group 2, patients with more than 50 per cent increase in monoclonal serum protein or development of monoclonal urine protein, 9 per cent; group 3, patients who died without five-year serum studies, 23 per cent; and group 4, patients in whom myeloma, macroglobulinemia or amyloidosis developed, 11 per cent. Initially, the hemoglobin level, size of serum monoclonal protein peak, number of plasma cells in the bone marrow and levels of normal immunoglobulins were not significantly different among the four groups. The median interval from recognition of the monoclonal protein to diagnosis of multiple myeloma was 64 months, of macroglobulinemia 103 months and of amyloidosis 92 months. A significant increase of the monoclonal protein or development of myeloma, macroglobulinemia or amyloidosis occurred in 18 per cent of the patients with monoclonal immunoglobulin G(IgG), in 28 per cent with immunoglobulin A (IgA) and in 25 per cent with immunoglobulin M (IgM). Retrospective analysis of age, sex, presence of organomegaly, hemoglobin level, size and type of serum monoclonal protein peak, presence of small amounts monoclonal light chain in the urine, serum albumin level, levels of uninvolved immunoglobulins, IgG subclass and level of plasma cells in the bone marrow did not show how to distinguish initially between stable benign disease and progressive disease. Therefore, periodic reexamination of patients with monoclonal gammopathy is essential.


Emphysematous pyelonephritis. A report of two cases.

Emphysematous pyelonephritis is a suppurative infection of the renal parenchyma characterized by the production of gas by bacteria through fermentation. Although seemingly rare, this condition occurred in two diabetic patients on general medical wards over a two year period. Diagnosis, in an appropriate clinical setting, is confirmed roetgenologically. Escherichia coli is the most common etiologic organism. Despite appropriate medical and surgical intervention, this severe form of renal parenchymal infection carries a high mortality.


Rheumatoid arthritis--a sequel to HBsAg hepatitis.

Reported here is the first case of classic rheumatoid arthritis emerging in the setting of hepatitis B surface antigen (HBsAG)-positive viral hepatitis. Polyfocal arthritis and myalgia, lymphadenopathy and constitutional symptoms were the presenting manifestations of anicteric hepatitis in this 23 year old man. Smooth muscles antibodies, HBsAg and "rheumatoid" factor were demonstrated initially. The hepatocellular disease, biopsy-proved, resolved completely and without recurrence; clinically and serologically. Latex test positivity persisted, increasing in titer, and polyarthritis progressed to fulfull criteria for classic rheumatoid arthritis, with erosions on roentgenogram and characteristic synovial disease. After 60 months of follow-up, the rheumatoid synovitis has continued to progress despite appropriate therapy. The arthritis of viral hepatitis and the significance of rheumatoid factor in association with hepatocellular disease are discussed.


Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis.

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.


Diabetes and hypoglycemia due to insulin antibodies.

A patient with "autoimmune diabetes" with reactive hypoglycemia due to anti-insulin antibodies is described. The pathophysiology of the impaired carbohydrate tolerance and reactive hypoglycemia is illustrated by measurements of C-peptide, and free and antibody-bound insulin. Detailed analysis of her antibodies did not provide any evidence in favor of exogenous insulin immunization. Nevertheless, a possible cause of unsuspected insulin immunization was present in her history which should be considered in other reported cases of "autoimmune diabetes" due to insulin antibodies in which exposure to insulin cannot be documented.


Unusual renal manifestations of Wegener's granulomatosis. Report of two cases.

Two patients with previously undescribed renal manifestations of Wegener's granulomatosis are described. A 24 year old man, who presented with typical necrotizing granulomatous sinus disease and cavitary pulmonary lesions, had multiple bilateral renal arterial aneurysms demonstrated angiographically. One of these aneurysms ruptured, leading to a massive perinephric hematoma. The bleeding artery was successfully occluded with Gelfoam embolization, thereby obviating the need for nephrectomy. A 60 year old woman presented with glomerulonephritis and mononeuritis multiplex two years before the development of classic necrotizing granulomatous inflammation of her sinuses and nose, along with pulmonary nodules. In addition, her left ureter became obstructed due to necrotizing vasculitis of the periureteral vessels. Both patients responded dramatically to cyclophosphamide therapy. The diagnosis of Wegener's granulomatosis should be considered in patients who present with multiple renal aneurysms, a spontaneous perinephric hematoma, necrotizing glomerulitis or ureteral obstruction due to vasculitis, even though the characteristic granulomatous respiratory involvement may be absent at that time. It is important to recognize these unusual renal manifestations as features of Wegener's granulomatosis because of the therapeutic efficacy of cytotoxic immunosuppressive agents in this disease.


Central nervous system histoplasmosis with obstructive hydrocephalus.

A case of central nervous system histoplasmosis complicated by obstruction of the fourth ventricle is described. The patient rarely exhibited systemic symtoms of infection despite positive cultures for Histoplasma capsulatum from bone marrow, blood and urine. Infection recurred despite the administration of a total of 5 g of systemic amphotericin B. An additional course combined with intrathecal amphotericin B was terminated because of transverse myelitis.


Successful treatment of Brucella melitensis end-carditis.

Brucella endocarditis is a rare, but often fatal, complication of brucellosis. A 32 year old man acquired brucellosis while on a visit to his former home in Greece and presented six months later with malaise, fever and aortic regurgitation. Blood cultures grew Brucella melitensis biotype 1. Combined chemotherapy with streptomycin, tetracycline and rifampin sterilized his blood; however, his aortic valve was replaced owing to recurrent emboli and cardiac failure. Over the next 18 months the patient's antibody titer to Brucella fell and his blood reamined sterile. Cure was achieved by resection of the infected aortic valve and 10 weeks of bactericidal therapy for B. melitensis.


Hypercalcemic crisis associated with the hypereosinophilic syndrome.

A patient with the idiopathic hyperosinophilic syndrome had severe, life-threatening hypercalcemia, a previously unreported complication of this unusual disease. Postmortem examination revelaed multiorgan eosinophilic infiltration and diffuse metastatic calcifications, but it did not disclose a definitive cause for the persistent hypercalcemia. It is concluded that the marked proliferation of eosinophils was the probable etiologic factor. Proposed mechanisms for this complication include (1) the destruction of bone by an expanding eosinophilic cell mass with subsequent calcium mobilization and (2) the production of a hypercalcemic humoral substance, possibly by the patient's eosinophils or as a consequence of their presence.


Malignant lymphoma of plasmablastic identity. A neoplasm with both "immunoblastic" and plasma cellular features.

A solitary extramedullary lymphoid neoplasm had characteristics of plasma cell precursors or plasmablasts. Conventional microscopic study classified this tumor as a diffuse large cell lymphoma of "immunoblastic sarcoma" type. Immunologic cell surface markers could not be detected, but cytoplasmic immunoglobulin G (IgG)-kappa was demonstrated by immunoperoxidase technic, and IgG was present in the supernatant of the tumor tissue culture. The distinction between lymphoid and plasma cellular neoplasms is made.


The interdisciplinary approach to laboratory medicine.

The clinical laboratory is a melting pot of diverse scientific experiences, perspectives, and approaches, all directed to the solution of particular medical problems. Integration of separate disciplines and areas of expertise is involved at serveral different levels of laboratory medicine. At the outset, one sees that any one area of the laboratory must depend upon all other laboratory areas for the proper interpretation of its data. Stated another way, all laboratory disciplines are involved in the integrated functioning of each individual area. Examination of the origin of analytical concepts fundamental to procedures and instruments utilized in the clinical laboratory leads one to realize that all areas of science contribute to laboratory medicine.


The cardiac profile.

The clinical laboratory furnishes information valuable not only in the diagnosis of myocardial infarction (MI), but also in screening for possible causes of ischemic heart disease through definition of the lipid status of individuals. Accordingly, the panels used in the study of hyperlipidemia as a possible cause of ischemic heart disease are reviewed, including the determination of serum cholesterol, triglycerides, and electrophoretic development of the lipoprotein pattern. The results of an on-going study of more than 500 patients admitted to the emergency room of a general hospital with symptoms of "chest pain" are presented--including the electrocardiogram, enzyme tests, and isoenzyme patterns, in conjuction with the clinical picture. The relative diagnostic value of test procedures is considered, convering the pre-enzymatic period, current test panels, and possible future approaches. It is concluded that the laboratory's position in providing data for diagnosis of MI would be enhanced through development of procedures with as great or greater specificity than the isoenzyme patterns of creatine kinase and lactate dehydrogenase, currently the most specific indicators of MI, but which have results available in two to five minutes.


Analytical interferences of drugs in clinical chemistry.

The effects of several drugs were tested on analytical methods used in the clinical laboratory to measure the concentration of certain chemical constituents and activity of enzymes in body fluids. Drugs were studied initially at reported toxic concentrations, but if they had an effect at this level effects of lower concentrations were also investigated. The drugs were first studied on the methods of the Technicon SMACTM analyzer. Subsequently, methods in use with the Du Pont ACA and Technicon AutoAnalyzerTM I or II were evaluated. The most commonly affected method was the phosphotungstate reduction procedure for measuring uric acid. However, methods for measuring total protein and albumin were also affected frequently, as were determinations of alkaline phosphatase and lactate dehydrogenase activity.


The emerging role of carcinodevelopmental antigens in the clinical laboratory.

Patterns of carcinoembryonic antigens (CEA) in fetal gut, seminal plasma, and amniotic fluids were investigated. In fetal gut the broadest range of CEA-expression occurred during the period of maximal mucosal differentiation. While normal adult colon or other fetal stages expressed lower quantitative and qualitative amounts of CEA, maximal CEA expression could be found in a pool of 20 primary adenocarcinomas of the colon. Low levels of CEA in seminal plasma were associated with subfertile, poorly differentiated sperm as opposed to CEA levels found in either normal ejaculates or those obtained from vasectomized, previously fertile males. In amniotic fluid CEA remained at a constant level between the 16th and 22nd week in utero as did fructose and urea levels. Glucose and histaminase levels showed great variance. The relationship of these latter findings to genetic defects is currently being investigated. These data suggest that an ever increasing number of biologic samples will be tested in the clinical laboratories for carcinodevelopmental antigen levels. These will be used for the prognosis and/or diagnosis of abnormal differentiation patterns in patients with cancer or in the developing fetus.


AMTEC: a cooperative effort in medical technology education.

A committee in the St. Louis Metropolitan area has been established to promote communication and cooperation among the area's existing hospital-based programs in medical technology. Area Medical Technology Education Coordinators (AMTEC) was established three years ago primarily to facilitate the administrative functions of medical technology education and to serve as an instrument for the exchange of ideas. Its primary undertaking has been the central processing of applications to the area programs, as an aid in the admission process. In addition, a continuing education program sponsored by the committee has been established, and various "curriculum sharing" activities have been sponsored for the students enrolled in the schools. Future plans for the committee include sponsoring an on-going evaluation process of graduates by employers, and establishing a criterion-referenced question pool. The authors describe the experiences of the committee to date and plans for the implementation of future goals.


Stem cells: a negative approach.

A discussion of the stem-cell concept from a negative point of view is presented to highlight the kinetics of the hematopoietic system. The negative approach documents the need for 318 pounds of stem cells to produce the red blood cells and neutrophils necessary to sustain a person for an average lifespan, assuming that the human organism did not have a self-sustaining pluripotent stem cell pool.


Hyperosmolar urea for elective midtrimester abortion. Experience in 1,913 cases.

Intra-amniotic hyperosmolar urea (59.7 per cent) augmented by intravenous oxytocin (332 millimicron per minute), prostaglandin F2alpha (20 mg.), prostaglandin F2alpha (10 mg.), or prostaglandin F2alpha (5 mg.) was utilized for 1,913 patients requesting elective midtrimester abortion. Injection-abortion intervals ranging from 13.70 to 21.49 hours were achieved with failure rates of 0.7 to 6.7 per cent. Despite frequent pre-existing medical conditions, the complication rate compared favorably with those of other methods for terminating midtrimester pregnancy such as saline amnioinfusion or dilatation and evacuation.


Intrauterine resuscitation with terbutaline: a method for the management of acute intrapartum fetal distress.

Terbutaline, a selective beta-2 adrenergic receptor stimulator, has been used to decrease myometrial activity and improve uteroplacental blood flow in 15 patients with acute intrapartum fetal distress. In all cases electronic monitoring gave evidence of partial or total fetal recovery after therapy. Thirteen of these patients were delivered by cesarean section and two were allowed to resume labor and deliver vaginally. In 10 cases the initial Apgar score was 7 or more and in all cases the score was 7 or more after 5 minutes of life. No significant maternal morbidity occurred as a consequence of the treatment. These results suggest that inhibition of uterine activity with terbutaline may be a valuable maneuver in the management of patients with severe intrapartum fetal distress.


Obstetric and psychological effects of psychoprophylactic preparation for childbirth.

Medical records, personal interviews about the childbirth experience, and self-administered attitudinal and socioeconomic data were obtained 1 to 3 days post partum in a large metropolitan hospital, for 249 women, 95 of whom had taken psychoprophylaxis training for childbirth prior to delivery. When controlled by parity, psychoprophylactic preparation was not related to any obstetric differences except for lower levels of anesthesia for both primiparas and multiparas and lower levels of analgesia among multiparas only. Preparation was significantly related to lower levels of pain and higher levels of enjoyment during childbirth, and these psychological benefits did not diminish when controlled for parity, socioeconomic status, and four sets of psychological and attitudinal characteristics.


Biological variation in the biparietal diameter and its bearing on clinical ultrasonography.

Interpopulation differences in the term BPD and its relations to BW stress the need for each institution to analyze its own data. Variations in the BPD as a function of BW do not connote differences in the brain: body weight relationship, because the neurocrania of all term fetuses are not homomorphic. Differentiation of neurocranial form accounts for there being no consistent relationship between the BPD and calculated brain weight in interpopulation comparisons. The wide scatter of BPD and BW values in data from a single source challenges the wisdom of judging individual serial BPD readings by mean population values. Because the correlation between BW and the common indices of maternal size (stature, weight, and surface area) is too low (r = 0.27, 0.27, and 0.35, respectively) to provide a useful means of determining the fetal growth potential, each fetus should be used as its own control in serial cephalometry.


Maternal peripheral testosterone levels during the first half of pregnancy.

Peripheral serum testosterone levels were determined in 180 women during weeks 7 to 20 of pregnancy with a specific radioimmunoassay. After a normal pregnancy and delivery 90 serum samples were randomly selected from mothers of boys and 90 serum samples from mothers of girls. The testosterone concentrations were correlated with the sex of the fetuses. The mean testosterone level +/- S.D. in pregnant women with female fetuses was 597 +/- 167 pg. per milliliter. In pregnant women with male fetuses the testosterone concentrations were on the average significantly higher (p less than 0.01), with a mean value of 828 +/- 298 pg. per milliliter. The course of the testosterone concentrations in women with male fetuses showed an increase beginning in week 7, reaching a maximum during weeks 9 to 11, followed by a decrease until weeks 15 to 20. During weeks 9 to 11 of pregnancy fetal sex determination was possible in 28 per cent of the males and in 5 per cent of the females, with a probability of 95.5 per cent.


Differentiation of amylase isozyme in amniotic fluid with fetal age.

Composition of the amylase isozymes in the amniotic fluid and their transition with fetal age were studied by means of thin-layer acrylamide gel electrophoresis. The results indicate that amylase isozymes in the amniotic fluid were composed of a pancreatic type faint major isozyme and several salivary type isozymes consisting of an intense major and a few less intense minor bands. Characteristic changes in the pattern of these isozymes with fetal age consisted of a marked increase of the salivary type isozymes rather than of the pancreatic type isozyme. A densitometric analysis of the isozyme patterns proved that the ratio of the pancreatic type isozyme to the salivary type major isozyme was highly correlated with fetal age regardless of levels of amylase activity.


Human placental lactogen, estradiol-17beta, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy.

Plasma levels of HPL, P, and E2 was serially measured between weeks 30 to 36 in simplex and duplex pregnancies. Levels of both HPL and P were significantly higher in duplex than in simplex pregnancies. However, this was not the case for E2. There was a significant correlation between HPL and P levels. It is indicated that measurement of plasma P levels, as those of HPL levels, but not E2 levels is of value for detecting twin pregnancy.


Developmental patterns of intestinal disaccharidases in human amniotic fluid.

A close relationship exists between relative disaccharidase activities (maltase, sucrase, trehalase, palatinase, turanase, lactase, and cellobiase) in amniotic fluid and corresponding jejunal mucosa of five human fetuses (16 to 21 weeks of gestation) suggesting that these intestinal enzymes pass into amniotic fluid. Serial determination of disaccharidase activities in amniotic fluid samples collected between 10 and 42 weeks of gestation showed maximum mean activities at 14 to 17 weeks of gestation and a rapid drop to less than 12 per cent maximum values at about 22 weeks. This drop is probably caused by combined effects of decreased extrusion rate of intestinal disaccharidases and increased reabsorption of the enzymes in swallowed amniotic fluid with fetal development.


Role of endocervical curettage in colposcopy.

A series of 1,850 patients with atypical Papanicolaou smears referred to the Colposcopy Clinic at Cook County Hospital were evaluated. There were 2,000 colposcopic examinations with or without directed biopsy and 495 endocervical curettements. Records of 126 patients who had definitive diagnoses were reviewed. Of 126 patients, 41 had diagnostic conization following colposcopy-directed biopsy and endocervical curettage; 85 had only colposcopy-directed biopsy and endocervical curettage. There were two instances in which an invasive cancer was missed prior to therapy, one in the group of 41 patients (incidence of 2.4 per cent), the other in the group of 85 patients (incidence of 1.1 per cent). Cone biopsy contributed very little to establishing the diagnosis of invasive cancer following colposcopy-directed biopsy and endocervical curettage. Safety measures for endocervical curettage performed during pregnancy are presented. The management of patients evaluated by colposcopy-directed biopsy and endocervical curettement requires careful correlation of histo- and cytopathology.


A new technique for and additional experience with hysteroscopic resection of submucous fibroids.

New instrumentation and a new technique are described which simplify the hysteroscopic removal of the pedunculated submucous fibroid and make possible the partial removal of the sessile variety. Experience with the method is presented including the follow-up of four patients.


Salpingo-oophorectomy at the time of vaginal hysterectomy.

Three hundred fifty-five cases of vaginal hysterectomy associated with bilateral or unilateral salpingo-oophorectomy were reviewed to assess the safety and feasibility of adnexa removal when such was necessary or desirable. Other than one instance of hemorrhage from ovarian vessels, no serious complications, including ureteral injuries, could be assigned specifically to the removal of the adnexa. Our opinion is that the techniques for salpingo-oophorectomy at the time of vaginal hysterectomy should be taught to residents and practiced by gynecologic surgeons.


Practical considerations for the routine application of left lateral Sims' position for vaginal delivery.

The lateral Sims' position was evaluated for routine use in vaginal deliveries. The study demonstrates that delivery in the lateral Sims' position is practical and easily mastered; most easily applied for spontaneous or uncomplicated outlet forceps delivery; of special advantage in breech deliveries, congestive heart failure, hip joint restriction, and leg varicosities; and well accepted by women looking for a less restricted and more natural delivery experience.


Cooper ligament repair of vaginal vault prolapse twenty-eight years later.

Sir Astley P. Cooper, a British surgeon, first described Cooper's ligament in 1841; in 1949 this ligament was, to our knowledge, first used to support prolapse of the vaginal vault. The first preliminary report in 1965 was based on anatomical dissection of 60 autopsy cases and stressed mainly the length, thickness, width, and strength of the Cooper ligament strip and the adjacent fascia overlying the symphysis pubis. The preliminary report suggested that this was indeed a strong fascial support and would support the vaginal vault. Since 1965, some 85 cases have been treated and in each case, since 1965, every effort has been made to incorporate all of the available extra fascial planes in the pelvic structure to add further support to the vaginal vault prolapse. No major complications have been encountered. The risk of infection of Mersilene strips and synthetics is avoided by using homologous Cooper ligament strips and adjacent fascia. No postoperative stress incontinence was encountered in any of the 63 cases.


The effect of glucocorticoids on the maturation of premature lung membranes. Preventing the respiratory distress syndrome by glucocorticoids.

The effect of glucocorticoid on the maturation of premature lung membranes was studied in 121 premature infants by administering variable dosages of Decadron to the 114 mothers prior to delivery. The results were compared with findings in a group of 390 infants born in the same hospital during this study. Administration of all three test doses, 8, 16, and 24 mg., significantly decreased the incidence of RDS in all gestational age and birth weight categories. For infants less than 32 weeks, the incidence was decreased from 75 to 46.2%; those 32 to 36 weeks, from 58 to 20.2%; and in those older than 36 weeks, from 24.4 to 0 per cent. The incidence in infants less than 1,000 grams was reduced from 100 to 71.5%; 1,000 to 1,500 grams, from 67.4 to 21.6%; 1,500 to 2,000 grams, from 52.3 to 22.6%; and in heavier than 2,000 grams, from 38.1 to 13.4%. The results also showed that glucocorticoid does not significantly reduce RDS if administered less than 24 hours prior to delivery. The incidence is reduced more than 50% if administered more than 24 hours prior to delivery.


Pelvic abscess in association with intrauterine contraceptive device.

Serious pelvic infection associated with the use of IUDs is of increasing concern to obstetricians and gynecologists. This review of the literature is accompanied by analysis of 5 years' experience at the Arizona Health Sciences Center. Of 169 patients with acute infections, 34% had an IUD in place at the onset of infection. In addition, 24 of the patients were less than 20 years of age and 35% were nulliparous. Of the nulliparous patients, 11 were rendered sterile following surgical extirpative therapy. Sixty-six patients developed pelvic and tubo-ovarian abscesses; 38% of those were related to IUD usage. Six of the pelvic abscesses and eight of the unilateral tubo-ovarian abscesses came to pelvic cleanout. Evidence presented documents the serious infection potential that IUD usage entails, the antibiotic and surgical management, the infertility that results, and the mechanism assumed responsible. In addition, the high-risk patient has been identified (young, nulliparous, sexually active, and, especially, of the lower socioeconomic strata).


A computerized perinatal data system for a region.

The development of regionalized systems for perinatal care requires a record system which will provide a flow of patient information to and from referring and center hospitals. It should also provide for the risk evaluation of patients being cared for within the region as well as for the quality and statistical evaluation. When the Arizona Perinatal Program was established in 1975 with funding by the Robert Wood Johnson Foundation, the decision was made to adopt and expand a perinatal data system under development at St. Joseph's Hospital in Phoenix. This data system is made up of two major components: (1) a paper record system in which the documents completed by physician or nurse serve both as the medical record and a computer-input document and (2) a computer capable of simultaneous communication with 17 different terminals, directly or by telephone lines. Programs to meet the goals of patient care, quality evaluation, and statistical assessment are described.


Stage II endometrial carcinoma: two modalities of treatment.

Forty-five cases of Stage II endometrial cancer are analyzed with regard to histologic grade, therapy, site of recurrence, survival, and cause of death. This group represents 5% of all endometrial cancer patients registered at the Southern California Cancer Center from 1954 to 1974. Thirty-two (71.2%) were classified as poorly differentiated tumors. A significant analysis of survival data comparing the 26 patients treated by RT alone, and 17 patients managed by surgery and RT, could not be obtained because of the small number of patients. However, the frequency of residual tumor in the uterus and intraperitoneal recurrence in the RT only group suggests that RT plus surgery should provide a better survival than RT alone.


Massive peripheral giant-cell reparative granuloma of the jaw: a pregnancy dependent tumor.

The case of a pregnant patient with giant-cell granuloma is presented. Differential diagnosis and treatment are discussed and the literature is reviewed.


The randomized management of term frank breech presentation: vaginal delivery vs. cesarean section.

A prospective study of the management of term frank breech presentation is currently ongoing at LAC-USC Medical Center. To date, 57 patients have been randomized to an elective cesarean section group and 70 to a vaginal delivery group. Of the 70 patients selected for vaginal delivery, 35 had one or more inadequate pelvic measurements by x-ray pelvimetry and were scheduled for indicated cesarean section. Of the remaining 35 patients in this group, 30 delivered vaginally without perinatal death. Two of the infants, however sustained brachial plexus injuries. Of the 57 patients scheduled, 55 underwent elective cesarean section. There were no maternal deaths, but 20 (36.4%) patients experienced morbidity and 5(9.1 per cent) patients experienced intraoperative complications. Based on the data accumulated to date, it seems reasonable to allow vaginal delivery in carefully selected cases of term frank breech presentation.


Crohn's disease: "its gynecologic aspect".

An analysis of the medical records of 103 women with Crohn's disease points up the following observations. There is a slight increase in spontaneous abortions and a substantial degree of subfertility. The obstetric experience is the same as in the normal obstetric population and the effects of the disease on pregnancy and of pregnancy on the disease are minimal. Features seemingly unrelated to Crohn's disease and of a gynecologic nature may be present months before the onset of the main bowel inflammation. These features consist of abscesses, fistulas, ulcers, fissures, and infections involving not only the internal pelvic organs but also the vulvovagina, perineum, labia, rectovaginal septum, rectum, and anus. The onset of Crohn's disease may be acute and present the picture of an abdomen requiring surgical treatment. A tender, low abdominal, adnexal, or pelvic mass may incorrectly be diagnosed as acute appendicitis, pelvic inflammatory disease, or ovarian cyst, and lead to surgery. In 23 instances the diagnosis of Crohn's disease was established only after laparotomy. A total of 27 appendectomies were performed and none of these patients had acute appendicitis. Four pelvic abscesses developed after the appendectomies. To avoid the pitfalls of misdiagnosis and mismanagement, the nature of Crohn's disease should be understood and the gynecologic aspects of the disease recognized.


Transabdominal repair of cystocele, a 20 year experience, compared with the traditional vaginal approach.

In patients with pelvic floor relaxation and concomitant pelvic pathology indicating the abdominal approach the so-called "combined" operation is not a satisfactory technique. During the course of the total abdominal hysterectomy the cystocele can well be repaired by mobilizing the bladder and excising the relaxed vaginal mucosa. The technique is described and its efficiency in 76 cases is compared to 109 cases repaired by the traditional vaginal approach. Over a 20 year period, 92% of the former as compared to 78% of the latter showed a satisfactory result. Both series revealed that time plus anatomic stress are the major factors in those patients in whom the pelvic floor relaxation recurred.


The primary-care physician and cancer detection: the role of the Pap smear.

This is a retrospective 5 year study of cancer detection in the suburban office of a primary-care physician. There were 127 diagnoses of malignancy confirmed in 5,011 patients, 62 in the reproductive system and 62 in other organ systems. More than 9,000 Pap smears resulted in the final diagnosis of carcinoma of the cervix in only seven patients. 374 curettages yielded 37 cases of endometrial carcinoma. All of these patients had Class I Pap smears preoperatively.


Intramural pregnancy with uterine rupture: a case report.

A case of intramural pregnancy is presented which mimicked early abruptio placentae and was associated with placenta percreta. The literature is briefly reviewed.


Growth regulators in connective tissue. Systemic administration of an aortic extract inhibits tumor growth in mice.

A low-molecular-weight fraction prepared from extracts of bovine aorta inhibits the growth of a transplantable mammary tumor and a fibrosarcoma in mice when injected systemically. It also inhibits the growth of the fibrosarcoma in cell culture. The effect on the fibrosarcoma is much more marked than on the mammary tumor. Since the extract is more effective against the fibrosarcoma and is known to inhibit the growth of endothelial cells, it appears that the enhanced effect on this tumor is due to its activity on the endothelial cells of the host and the tumor cells themselves. The material injected is enriched in an antiproteinase we have previously isolated, which has anticollagneolytic activity and is presumed to be the effector molecule.


Differences in peroxidase localization of rabbit peritoneal macrophages after surface adherence.

Unlike resident peritoneal macrophages, which contain peroxidase in the rough endoplasmic reticulum (RER) and perinuclear cisternae (PN), macrophages elicited into the rabbit peritoneal cavity by various stimulants lack the enzyme. Since we had previously found that such peroxidase reactivity rapidly appears in the RER and PN of blood monocytes after surface adherence in vitro, we wondered whether the enzyme could be similarly produced in elicited macrophages by adherence. Cells from peritoneal exudates (96 hours after endotoxin injection) were harvested, suspended in culture medium, and allowed to adhere to fibrin-coated or plastic surfaces. Following culture for various intervals, they were fixed, incubated for peroxidase, and examined by electron microscopy. We observed that these elicited cells, which initially contained no cytochemically detectable peroxidase, acquired peroxidatic activity in the RER and PN within 2 hours after adherence in culture. Thus macrophages, like blood monocytes, may rapidly acquire peroxidase reactivity as a consequence of plasma membrane: external surface interaction. In view of this finding, it would seem unwise to use peroxidase localization as the basis for advocating the existence of two separate lines of peritoneal macrophages, as has been proposed by previous investigators.


Effect of gonadectomy on the follicular cell and inclusions in mitochondria of rabbit thyroid gland.

Thyroid glands of male rabbits were studied 2, 4, and 6 weeks after gonadectomy. In the gonadectomized group of animals, at the end of 2 weeks the follicular cell did not present any significant change except for the reduction of the supranuclear portion of the cell. By the end of 4 weeks there was a marked decrease in the microvilli of the apical border, dense granules, colloid droplets, ribosomes, and ergastoplasmic sacs. The lateral and basal cell margins were less convoluted. These changes reached a peak by the end of 6 weeks. The mitochondria with the inclusions also showed an apparent decrease in incidence at the end of 4 weeks and were rarely encountered by the end of 6 weeks. The thyroid gland morphologially resembled a hypothroid state, indicating that gonadectomy depresses the function and, therefore, may affect the metabolic process controlled by the gland.