Evaluation of transbronchial biopsy of the lung. Transbronchial biopsy of the lung through the fiberoptic bronchoscope is becoming a widely utilized clinical diagnostic technic. The authors reviewed the histologic features of 109 consecutive cases. The primary problem is the small size of the pulmonary tissue samples obtained, which is further compounded by an apparent mechanical inability to enter the biopsy forceps into dense nodules of neoplastic tissue. The diagnosis of carcinoma can best be made by examining the periphery of the cancer for microscopic extension into adjacent pulmonary parenchyma; however, multiple levels of the tissue block are needed to find such foci. A second problem reflects the use of transbronchial biopsy in the early clinical evolution of various infectious diseases in which pulmonary tissue may contain organisms without a fully developed inflammatory response, which would ordinarily provide the clue to the infective agent. The latter problem appears in cases of infections by Pneumocystis carinii. Close cooperation between the clinician and the pathologist is particularly important in all of these clinical situations.


The perilobular hemangioma. A benign microscopic vascular lesion of the breast. Vascular tumors of the breast are rare, and reports in the literature suggest that most are malignant. The present study is concerned with a benign vascular tumor of the breast, a lesion generally known as perilobular hemangioma. This microscopic lesion consists of a meshwork of thin-walled, dilated vascular channels that may be situated within a breast lobule or in the extralobular mammary stroma. Hemangiomas of this type were found in seven or 1.2% or 555 mastectomies performed in 1974 in female patients who had mammary carcinoma. There was no association with a specific type of mammary carcinoma. Similar hemangiomas were observed as often in a series of breast biopsies performed for benign conditions. None of the angiomas showed any significant atypia or anaplasia.


Comparison of the reaction-rate and clot-density methods for determination of plasma fibrinogen. The reaction-rate (Dade) and clot-density (Sherwood) methods for determining plasma fibrinogen were compared. Both require small sample volumes, are economical, and may be performed using commercially standardized instruments and reagents. Equivalent times were required for sample preparation. The results of the fibrinogen determinations were similar for plasmas of normal subjects, reference plasmas, those from patients with and without disseminated intravascular coagulation, and solutions of bovine fibrinogen. Both procedures could be made more economical by adjusting the amounts of certain reagents in the kits. High fibrin degradation product levels had no effect on the fibrinogen determination by either method. Advantages of the Sherwood method included digital readout (obviating further calculations) and the fact that the change in clot density could be plotted. The Dade method had the advantages of being less affected by high concentrations of heparin, being applicable to either citrated or oxalated plasma, requiring considerably less time (especially for certain abnormal plasmas), and requiring less technical sophistication.


An evaluation of a kinetic acid phosphatase method. The authors have evaluated a new kinetic acid phosphatase method in which the substrate is alpha-naphthyl phosphate. The original claim that this substrate was highly specific for the prostatic isozyme has been strongly challenged. Therefore, large numbers of patients in the following groupings were included in the evaluation: 52 urology clinic patients, 17 patients with uremia, 11 patients with multiple myeloma and 231 patients who had undergone prostatic biopsies. Two hundred seventy of these patients were found to be free of prostatic cancer. Of these, seven had acid phosphatase values above the upper limit of normal. Five of these seven patients had diagnoses of fibromuscular glandular hyperplasia. One was a woman who had multiple myeloma, and one was a uremic patient. Fifteen of 17 patients who had metastatic cancer of the prostate had elevated acid phosphatase activities, whereas one of 24 patients who had cancer of the prostate but no evidence of metastases had an elevated value.


Upper cervical myelopathy in achondroplasia. Two achondroplastic infants had small foramina magna with lethal compression of the corresponding upper cervical spinal cords. The damage was histologically comparable to the hyperextension type of spinal cord injury. An anterior displacement of the foramen magnum was demonstrated in one of the two cases. The displacement is considered worthy of future verification as it may be an additional factor in susceptibility to hyperextension injury to the spinal cord. The second patient survived 6 months, demonstrating that not all upper cervical spinal cord injuries are immediately fatal. Patients who have sublethal lesions are potentially salvageable by surgery. It is also speculated that there might be more cases of nonlethal upper cervical spinal-cord damage in achondroplasia, especially in early infancy when infants are unable to hold their heads erect. The true incidence of slight upper cervical spinal cord damage is not known, although it is considered rare at present. As a result of the findings in these two cases, it is suggested that hyperextension of the head be avoided, when possible.


False-negative test for fibrinogen--fibrin degradation products. The tanned red cell hemagglutination inhibition immunoassay has proved to be a sensitive test for the measurement of fibrinogen-fibrin degradation products (FDP-fdp). The case of a patient who initially had a negative test for FDP-fdp due to the presence of an anti-D antibody and the use of O-positive tanned erythrocytes in the hemagglutination inhibition immunoassay is presented. When a control consisting of buffer substituted for the anti-fibrinogen antiserum, tanned erythrocytes and patient's serum is used, the agglutination due to incompatibility will be recognized. The irregular antibody can then be removed by absorption, and the titer for FDP-fdp can be accurately measured.


Hepatitis B surface antigen and chronic hepatitis in infants born to asymptomatic carrier mothers. Twenty-three infants born to asymptomatic hepatitis B surface antigen (HBSAg) carrier mothers were followed up to determine the vertical transmission of hepatitis B virus. Four infants became positive for HBSAg within four months after birth. Three showed hepatic dysfunction; liver biopsy specimens demonstrated mild chronic hepatitis in one and persistent hepatitis in another. In six infants followed up for more than six months after birth, antibody to HBSAg (anti-HBS) without antigenemia could be detected. Antigenemia of cord blood strongly suggested that hepatitis B viral infection of the infant would occur. HBSAg was also demonstrated in breast milk by radioimmunoassay in three cases. These findings indicate that vertical transmission of hepatitis B virus occurs in many infants born to asymptomatic HBSAg carrier mothers, and that some of them become persistent carriers or develop chronic hepatitis without showing any signs suggesting hepatic involvement.


Androgens, estrogens, and the ultimate height in XO gonadal dysgenesis. We observed 40 patients with 45,X gonadal dysgenesis from the age of 13 to 15 years until the age of 18 to 21 years. The ultimate height of the 12 nontreated patients was 143.2 cm. Of 15 patients treated with nandrolone phenpropionate or methandrostenolone, the ultimate height was 143.3 cm, and of 13 patients treated with ethinyl estradiol, the height reached was 144.1 cm. The mean height of ten patients first seen at the age of 25 to 31 years was 140.1 cm. The mean height at any age was almost identical in all the groups. The growth velocity was somewhat accelerated by anabolic steroids and to a lesser extent, by estrogens only during the first year of therapy, and this did not influence the ultimate height. We saw no deleterious effects of the estrogens. In all the groups, there were patients who grew for some time at rates of up to 4 to 6 cm/yr. Therefore, long-term follow-up studies are needed for the evaluation of the effects of any treatment.


'Myelokathexis'. Neutropenia with marrow hyperplasia. A 10-year-old girl was first seen at age 5 years with pneumonia and neutropenia. Since then, she has remained leukopenic, although manifesting a leukocytosis only when she has pulmonary infection. A rapid fall in her peripheral WBC count occurs with initiation of antibiotic therapy. Despite her neutropenia, marked myeloid hyperplasia is evident on marrow smear examination; many cells being hypersegmented with fine intralobular bridging with chromatin strands and cytoplasmic vacuolation. The peripheral WBC response to epinephrine adminstration did not indicate a shift from the circulating to marginal neutrophil pool. Results from a Rebuck skin window test suggested poor neutrophil tissue migration. A defect in granulocyte release from the patient's marrow may explain these bizarre hematologic findings.


Aspirin-induced hepatotoxicity and its effect on juvenile rheumatoid arthritis. Evidence of hepatic disease was sought in 102 children with juvenile rheumatoid arthritis (JRA) who were treated with aspirin. Serum glutamic oxaloacetic transaminase level was elevated (greater than 39 IU/liter) in 59% of the children. The degree and prevalence of SGOT elevations correlated with aspirin dose and serum salicylate level. Nevertheless, increased SGOT values were frequently present in children receiving moderate aspirin doses and having serum salicylate levels less than 25 mg/100 ml. Elevated SGOT values decreased in proportion to the degree of reduction in aspirin dose. The SGOT values above the 100 IU/liter were statistically associated with reduced sedimentation rates. Concomitant improvement in the clinical manifestations of JRA was noted in some children.


The serendipitous diagnosis of mild hypothyroidism during childhood. A roentgenographic approach. Roentgenograms of the chest, hip, or hand performed for a variety of reasons, may provide findings indicative of hypothyroidism even before there are any clear clinical signs of the disorder. It is stressed that the alertness of the roentgenologist and/or the physician is an important factor in discovering mild changes of the disease. We present such roentgenologic findings and illustrative cases of patients who were examined because of repeated respiratory tract infections, suspected hip joint dislocation and, sluggish behavior.


Fibrous dysplasia of bone with proptosis. A case of fibrous dysplasia of the bone presented as monocular proptosis in a 10-year-old boy. The characteristics of the disease entity, differential diagnosis, and treatment are discussed.


Agammaglobulinemia, plasma cell dyscrasia, and amyloidosis in a 12-year-old child. A 12-year-old boy suffered from recurrent respiratory infections, an immune deficiency characterized by the complete absence of IgG, IgA, IgD, and the salivary "secretory component" associated with a plasma cell dyscrasia. Rectal and kidney biopsy specimens showed amyloid deposits. Amyloidosis has been extensively studied by several groups of investigators in patients with plasma cell dyscrasia in general, and in patients with lambda-Bence Jones proteinuria in particular, but the finding of a monocional serum IgM-lambda component in an agammaglobulinemic child with Bence Jones proteinuria and amyloidosis represents a puzzling clinical syndrome. Searching for monoclonal components in patients with amyloidosis, even if they are agammaglobulinemic, is important. We also discuss here the "mixed type" of amyloid deposition and its relation to the recurrent infections and the plasma cell dyscrasia in this patient.


High-altitude pulmonary edema in children. A 15-year-old boy with recurrent high-altitude pulmonary edema had previously been mistakenly treated for asthma and pneumonia. Clinical manifestations of this disorder, its etiology, treatment, and prevention are discussed.


Acute posterior fossa epidural hematomas in children. Epidural hematoma in the posterior fossa is a rare clinical entity requiring immediate surgical intervention to prevent rapid and fatal deterioration. This diagnosis should be considered in children with occipital head trauma who have altered sensorium and evidence of compression of structures within the posterior fossa. Such a clinical setting demands close neurologic observation in a facility where contrast studies and neurosurgical intervention are available. The absence of an occipital skull fracture or the presence of normal pulse rate and blood pressure should not influence the decision. Lumbar puncture is absolutely contraindicated.


Benzocaine-induced methemoglobinemia.

Benzocaine-induced methemoglobinemia. Severe methemoglobinemia developed in a healthy 14-month-old infant following the topical application of a benzocaine-containing gel administered for the relief of the discomfort of teething. Congenital methemoglobinemia and hemoglobin M disease were excluded by appropriate laboratory studies. The patient is considered to have a normal methemoglobin-reducing capacity and her response to the drug is one that presumably could occur in any other child of comparable age on receiving an equivalent dose of benzocaine. Parents should be cautioned against the indiscriminate use of similar medications, particularly since the process for which these medications are administered is both benign and physiologic.


Guillain-Barré syndrome. Another cause of the "floppy infant". We report a 4 1/2-month-old female infant with subacute onset of hypotonia. Symmetrical weakness, association with a viral illness, high CSF protein level, diminished nerve conduction velocities, and a prompt recovery were compatible with the diagnosis of Guillain-Barré syndrome. The possibility that this disorder may occur in young infants with weakness should be considered.


Hepatic sensitivity to imipramine.

Hepatic sensitivity to imipramine. A case of significant hepatic reaction related to imipramine is presented, documented by challenge with imipramine and liver biopsy. The mechanism, while not entirely clear, is presumed to involve hypersensitivity or induction of toxic metabolites.


Hypertrophic protein-losing gastropathy and vitiligo. Report of a second case. A second patient with hypertrophic protein-losing gastropathy and extensive vitiligo was studied. Upper gastrointestinal radiographs and endoscopy revealed multiple polyps of the upper half of the stomach. The patient was achlorhydric to pentagastrin stimulation. Clearance of 51Cr-labeled protein by the gastrointestinal tract was about 15 times normal. A total gastrectomy was done for relief of persistent epigastric pain and correction of hypoproteinemia. Histologically the polyps consisted of hypertrophied mucosal glands with cystic dilatation deep to the glandular layer. The similarity of this patient to a patient previously seen at our hospital led us to report the possible association of hypertrophic protein-losing gastropathy with vitiligo.


Cruveilhier-Baumgarten disease with associated splenic artery aneurysms. Cruveilhier-Baumgarten Disease is a rare clinical entity. The distinction between C-B Disease and C-B syndrome rests solely on the liver morphology. In C-B Disease, the liver is morphologically normal. A case of a 27-year-old juvenile diabetic female with C-B Disease is presented. She manifested many of the metabolic and hemodynamic changes of cirrhosis including portal hypertension, encephalopathy, and a hyperdynamic cardiovascular state. There was also associated splenomegaly, hypersplenism, and splenic artery aneurysms. Splenectomy and splenic artery ligation were performed. Liver biopsies had normal morphology. The patient has had no recurrence of her symptoms. The pathogenesis of C-B Disease is unknown.


The absence of bacteremia during colonoscopy. Seventy-nine blood cultures were obtained from 15 patients undergoing diagnostic colonoscopy. Aerobic and anaerobic culture technics showed no evidence of bacteremia during or after the procedure. The colonoscope was passed to the cecum in 12 of the 15 patients. The time of the procedure varied from 15-60 minutes with an average of 30 minutes. The results of this study supplies further evidence that bacteremia during colonoscopy is an infrequent occurrence.


Serum lysozyme levels in inflammatory bowel disease. Serum lysozyme levels were compared in patients with Crohn's disease (CD) and chronic ulcerative colitis (CUC) to determine if the two diseases could be differentiated by this parameter. The lysozyme concentrations were measured by three different methods: 1. the turbidimetric clearance of Micrococcus lysodeikticus utilizing egg white lysozyme as a standard; 2. the lysoplate assay of Osserman and Lawlor using a human lysozyme standard obtained from Dr. Osserman and 3. the lysoplate assay obtained as a commercial kit using human lysozyme as a standard. A series of 19 CD and 23 CUC patients were compared. Contrary to the report of Falchuk, et al, the serum lysozyme levels by any of the three methods were not statistically significantly different in the two diseases. The serum levels of those with severe, moderate, or inactive disease were also not significant for CD or CUC nor in serially followed patients did levels always correspont to changes in clinical course.


Infarction of the gallbladder: a complication of hypertension. Case report. A case of gallbladder infarction, occurring in a 34-year old man with severe hypertension is described, with uneventful recovery following cholecystectomy. In the absence of other obvious etiologic factors, the gallbladder infarction is presumed to be directly related to hypertensive vascular disease. Infarction of the gallbladder is rare; a few cases associated with hypertension have been previously reported. Other types of vascular disease including embolization, thrombosis complicating atherosclerosis and celiac angiography, polyarteritis nodosa, occlusion following torsion and cystic vein thrombosis have been reported to cause gallbladder infarction.


Pancreatic ascites. Calcification as a clue to diagnosis. Pancreatic ascitis in a 31-year old black male is described. The diagnosis was suspected by the presence of pancreatic calcifications and confirmed by an elevated ascitic fluid amylase and protein content. Ascites was successfully treated by caudal pancreatectomy followed by a Roux-en-y pancreatojejunostomy.


Risk factors and early diagnosis in pancreatic carcinoma. A case is reported of pancreatic carcinoma recognized four years after bile peritonitis complicated cholecystectomy. The patient possessed all the known significant risk factors associated with pancreatic carcinoma. The wider recognition of risk factors for pancreatic adenocarcinoma might lead to closer follow-up of patients with multiple factors and possible earlier diagnosis and treatment leading to increased survival in patients with the disease.


Adult hypertrophic pyloric stenosis. Report of an unusual case detected by saline load test. A case of adult idiopathic hypertropic pyloric stenosis whose radiographic study was repeatedly normal is presented. Only a functional test of gastric emptying disclosed the degree of outlet obstruction present. Vagotomy and pyloroplasty resulted in prolonged relief of obstructive symptoms and a return of the saline load test to normal. The saline load test may be of value when gastroduodenal x-rays or endoscopy do not reveal the cause or extent of gastric outlet obstruction.


Giardia lamblia. A case presentation of chronic cholecystitis and duodenitis. A case of chronic cholecystitis and duodenojejunitis secondary to Giardia lamblia is presented. Though well documented as a cause of duodenitis, this condition is not a common finding in the United States and hence the diagnosis is not made routinely. This case illustrates an instance where giarditic duodenojejunitis may have been masquerading as a chronic cholecystitis.


Vascular compression of the duodenum.

Vascular compression of the duodenum. A successfully treated case of vascular compression of the duodenum is presented. The associated factors that might have been involved in predisposing this patient to the development of an acute intermittent, yet worsening clinical picture, are discussed, as well as the possible precipitating factor. Diagnosis and management of this disease entity are discussed.


Long-term results in the treatment of regional ileitis with coherin. Nineteen patients with severe symptoms of ileitis, not responsive to other forms of therapy, have been treated with coherin, a peptide isolated from bovine posterior pituitary glands. This study encompasses observations over a total of 50-patient years. tcoherin has proven efficacious by three criteria: As a result of coherin treatment those patients receiving steroids could either eliminate them or reduce the dosage to safe levels. A significant number of patients whose symptoms have been controlled by coherin have demonstrated their therapeutic dependence on coherin for relief of symptoms by multiple unsuccessful attempts to discontinue treatment over a long period of time. Diarrhea, in patients with ileitis symptoms, is effectively controlled by coherin therapy on a long-term basis.


The roentgenographic demonstration of a gastric mucosal laceration (Mallory-Weiss Lesion). The Mallory-Weiss lesion is responsible for many cases of upper gastrointestinal hemorrhage. Rapid diagnosis should be obtainable by endoscopic procedures. During active bleeding, angiography is the radiologic procedure of choice. The upper gastrointestinal series has been considered of little diagnostic use. Our case emphasizes that it may add valuable information when particular attention and careful technic are paid to the esophagogastric area.


Epidemiologic characteristics of benign breast disease. To see if the risk factors associated with fibroadenoma and cystic disease were similar to those reported for breast cancer, a retrospective study of benign breast tumor in a general population was conducted in Washington County, Maryland. The study population consisted of 320 white women 20 to 49 years of age who had had benign breast disease and 320 age-matched controls. More cystic disease cases than controls had the following characteristics, which had been reported to have been associated with breast cancer in other studies: higher socioeconomic status; fewer pregnancies; and a lack of association with lactation patterns. Nulliparity, late natural menopause and a maternal history of breast cancer were also more common among cystic cases than controls, although these differences could have occurred by chance. Cystic disease cases and controls did not differ with respect to other factors associated with breast cancer, such as early age at menarche, late age at first pregnancy, and negative history of artificial menopause. In contrast to cystic breast disease, fibroadenoma was not associated with most of the risk factors of breast cancer.


Maternal smoking and birth weight.

Maternal smoking and birth weight. To determine whether it is the smoker or smoking per se that explains the observed reduction in birth weight of infants of mothers who smoked during pregnancy, data collected on 1016 pairs of successive births which occurred between 1946 and 1963 in Washington County, Maryland, were studied. The mean birth weight difference between first and second members of pairs of consecutive live births of the same mother was examined in relation to her smoking habits during both pregnancies. A multiple regression technique was used to simultaneously adjust for the effects of maternal smoking habits during pregnancy, infant sex, maternal age, and birth order on birth weight difference. There were no significant differences in mean birth weight difference among pairs in which the mother smoked throughout both pregnancies, pairs in which the mother was a nonsmoker during both pregnancies, and pairs in which the mother smoked during the second pregnancy of the pair, but not the first. When birth weights of only first members of the pair were studied, the mean birth weight of infants of women who were nonsmokers throughout both pregnancies was higher than that of infants of women who smoked during both pregnancies. Infants of first members of pairs in which the mothers smoked only during the second pregnancy tended to have birth weights which were lower than that of infants of nonsmokers and higher than that of infants of smokers. These findings neither confirm nor deny the hypothesis that the smoker rather than the smoking per se causes a reduction in birth weight.


Change in respiratory symptom prevalence in adults who alter their smoking habits. The prevalence of chronic cough and phlegm production has been studied in 3916 young married adults, with recent new births and young children in their families, on six consecutive annual occasions. Among those who were smokers, in all years of the study more men than women reported respiratory symptoms. Respiratory symptoms were also reported more commonly among men than among women who did not smoke at all, whereas no sex difference in symptom prevalence was apparent among men and women who changed their smoking habits during the study. Equal numbers of men stopped or started smoking on their own initiative during the second three years of the study, whereas twice as many women started smoking as stopped in the same period. Men who had been smokers in the first three years and who spontaneously stopped smoking during the second three years showed a progressive decline in respiratory symptoms to a level similar to that of nonsmokers.


Respiratory symptom prevalence in adults: the comparative importance of smoking and family factors. In a study of the prevalence of chronic cough and phlegm production in a group of nearly 4000 young adults, those adults who had several children had a higher prevalvalence of these symptoms than those with few children, especially if the children suffered from bronchitis or pneumonia. Nevertheless, cigarette smoking was the factor most strongly associated with chronic cough and phlegm production in young adults in this study.


Smoking habits and changes in smoking habits as they relate to chronic conditions and respiratory symptoms. The relation of smoking to chronic lung disease has been documented in several studies. Several conclusions have been drawn about the type of smoking associated withdisease, including inhalation, filter tip use, and reduction in smoking. These factors were examined in a community epidemiologic study of chronic obstructive lung diseases. It was found that the community population exhibited greater filter tip use and higher rates of exsmoking than often seen elsewhere. Smoking habits and the changes in smoking habits over time were related to physician-diagnosed emphysema and/or chronic bronchitis, but not asthma. Some relation was seen also with present heart trouble. There was dose-relationship to pack-years of smoking in both present and ex-smokers. There were more ex-smokers among males. Most male ex-smokers quit due to symptoms. Ex-smokers were found to have high rates of diagnosed disease but reduced rates of symptoms. The incidence of diagnosed disease was found to be associated with smoking, both in intensity and duration. Changes in smoking over time were found to be correlated with symptomatology.


The relationship of acute respiratory illness history to the prevalence and incidence of obstructive lung disorders. Several studies have suggested that acute respiratory illnesses (ARI) may be precursors to chronic obstructive lung diseases, as well as being exacerbations of such diseases. The relationship of retrospective and prospective data on ARI to the prevalence and incidence of obstructive lung disorders has been examined in the community epidemiologic study of obstructive diseases a longitudinal study in Tucson. It has been determined that both the previous and subsequent history of ARI are significantly associated with the prevalence and incidence of airways obstructive diseases, those diagnosed by physicians and those inferred by symptoms. Lung function impairment also appears to be associated with such illnesses. This study implicates ARI as one of the major factors associated with the etiology as well as the natural history of chronic obstructive lung disease.


The sudden infant death syndrome among Alaskan natives. Among Alaskian natives the sudden infant death syndrome (SIDS) occurs at a rate somewhat less than that reported for native Americans indigenous to temperate latitudes. Cases occurred in both the arctic and subarctic regions of the state and among all but one of the ethnically distinct native population groups. No striking male predisposition was evident. These findings are, in general, similar to previously reported accounts from the states of California and Washington. Any theory of SIDS epidemiogenesis must take into account its wide geoethnic and peculiar sex distribution.


Army rank and subsequent mortality by cause: 23-year follow-up. Mortality among veterans has been studied in relation to military rank at separation in a series of 85,491 men discharged from the US Army in 1946 and traced through 1969. It was found that although the mortality of privates was very close to expectation based on population rates, non-commissioned officers had a 23% advantage and commissioned officers about a 40% advantage. The relative advantage of the veterans who had higher rank held not only for deaths from all causes but also for most of the specific causes examined and there was only a small tendency for the differences to diminish with the passage of time during the 23-year period of follow-up.


Analysis of prospective epidemiologic studies by minimum distance case-control matching. This paper presents the use of a matching method for analysis of prospective epidemiologic studies which generate a relatively small number of cases of a given disease. In such studies, matching in the manner presented may be of a given disease. In such studies, matching in the manner presented may be superior to other methods of analysis in removing bias due to confounding. A multivariate minimum-distance matching algorithm is used for computer selection of controls for the cases and the method is illustrated by application to a prospective cardiovascular disease study. The main advantages are that the results are easy to understand and interpret, and that there is no possibiligy of bias due to confounding variables when close matches are obtained. In contrast, the results of multivariate analysis may be difficult to understand and interpret, and the removal of bias due to confounding is dependent on the assumptions of the mode. It is recommended that the matching method should be used in addition to and at times stead of other methods of analysis whenever a study involves a relatively small number of cases and a large source of controls of controls on whom relevant study variables have already been documented.


Epidemiologic screening: a method to add efficiency to epidemiologic research. The concept of power loss through misclassification is well known. A simple method developed here yields a means for determing by how much power is lost. The method provides the basis for the development of an efficient screening methodology for the identification of high and low risk cohorts. This screening procedure is built on the well established retrospective cohort methodology and utilizes general records of mortality and morbidity for determination of the frequency of disease in the exposed and non-exposed cohorts. The size and power of the testing procedure compare favorably to that of a study with complete follow-up, while reducing the time and costs of study. This is particularly important in aiding epidemiologists in determining research and program priorities from among many areas of possible concern.


The reporting of communicable diseases.

The reporting of communicable diseases. Surveillance of communicable diseases in the United States depends on the reporting of cases by primary physicians. It is widely recognized, however, that significant numbers of such cases are not reported. Reporting rates for many communicable diseases have never been determined. In this study, discharge records of 11 hospitals in Washington, DC were searched for cases of selected communicable diseases, and the percentage of these cases reported was determined. Five hundred and seventy of 93,563 (0.61%) patients hospitalized over the study period had one of these communicable diseases. Reporting rates for each were as follows: viral hepatitis, 11%; H. influenzae meningitis, 32%; salmonellosis, 42%; meningococcal meningitis, 50%; shigellosis, 62%; tuberculosis, 63%; total cases, 35%. There is indirect evidence that low reporting rates are not restricted to the area studied. Supplemental reporting by medical laboratories, hospital infection control, and record room personnel were suggested as additional soruces of case reports.


alpha-Thalassemia and beta-thalassemia in a Turkish family. A Turkish family is described in which three children have a clinical picture similar to that of thalassemia major, with typical red cell morphology and indices, and with about 10% Hb Bart's but without measurable amounts of Hb H. Hematological evaluation of six members of this family that included in vitro hemoglobin synthesis suggests that beta-(or delta beta-) thalassemia, beta-silent thalassemia, and mild and severe alpha-thalassemia genes are present in different combinations. The data indicate that beta/alpha chain ratios in patients with more than one type of thalassemia should be evaluated in relationship to values obtained for several relatives even though some of the thalassemia determinants may be silent in the parents.


Sickle cell anemia: erythrokinetics, blood volumes, and a study of possible determinants of severity. The variability in the clinical expression of sickle cell anemia led us to study factors which might influence the course of this disease. We examined erythrokinetics, blood volumes, and variables which influence hemoglobin function in a group of adults with sickle cell anemia of varying degrees of clinical severity. We were unable to correlate any single measurement with the clinical course; however, our patient sample was small and the data suggested areas for further study. An expansion of plasma volume noted in all patients. This made it difficult to predict red cell mass from the hemoglobin level, which consistently underestimated its magnitude. The red cell production index and iron turnover values indicated that there is often a suboptimal erythropoietic response to anemia in sickle cell disease.


Sickle cell anemia and trait in a population of southern India. In an ethnic group in southern India, the Irula, seven individuals with sickle cell anemia were found to manifest only mild illness. Although a relatively high level of fetal hemoglobin was present in one, none of the factors thought to ameliorate the course of sickling disorders could be identified in the remaining six. In a random population survey, sickle hemoglobin was found in 90 of 292 Irula (31%). In those with sickle cell trait, the proportion of sickle hemoglobin in hemolysates (mean = 26%, range 19-32%) was substantially lower than that reported for any other population.


A family study of a patient with idiopathic hemochromatosis. A family study of a patient with idiopathic hemochromatosis using noninvasive techniques is presented. All 6 of the patient's asymptomatic children had an increase in transferrin saturation and/or an increase in the absorption of Co57. The Co57 absorption test was the most sensitive index of family involvement since one of the children had an increase in absorption at a time when transferring saturation was normal. The family data strongly support the hereditary nature of the disorder, with the mode of inheritance not clearly established from the available data.


Hydrogen peroxide, an inhibitor of platelet function: effect on adenine nucleotide metabolism, and the release reaction. The in vitro effects of H2O2 on platelet adenine nucleotide metabolism and on the ADP-induced platelet release reaction were examined. All studies were performed on human platelet-rich plasma (PRP) preincubated with (3H)-adenine. Within 3 min of incubation with PRP, H2O2 (100-500 micronM) caused an irreversible reduction in the (3H)-ATP level with a concomitant increase in (3H)-IMP and (3H)-inosine and hypoxanthine levels. The adenylate energy charge (AEC) initially decreased while the ATP level fell. The AEC, however, returned to levels slightly lower than the control during further incubation. No leakage of ATP and ADP to plasma was observed. The fall in the steady-state levels of (3H)-ATP increased with increase of the H2O2 concentration (decrease of 8.7-40% at H2O2 concentrations from 5 to 600 micronM). H2O2 pretreatment of PRP caused absence of ADP-induced biphasic aggregation, partial inhibition of the primary wave, and complete inhibition of release of platelet nonmetabolic ATP and ADP. Our in vitro findings support the view that part of the inhibitory effect of H2O2 may be related to the lowering of metabolic ATP levels in platelets.


Detection of drug-dependent antibodies by the 51Cr platelet lysis test: documentation of immune thrombocytopenia induced by diphenylhydantoin, diazepam, and sulfisoxazole. Sudden, severe thrombocytopenia developed in each of three patients receiving diphenylhydantion, diazepam, and sulfisoxazole, respectively. Recovery followed discontinuance of the drugs. An antiplatelet antibody requiring the presence of an appropriate drug for interaction with platelets was deomonstrated in each case by the 51Cr platelet lysis test using normal, paroxysmal nocturnal hemoglobinuric, or enzyme-treated normal platelets as target cells. These antibodies could not be detected by techniques that depend on clot retraction inhibition, complement fixation, or platelet factor-3 activation. Quinine-and quinidine-dependent antiplatelet antibodies in the serum of 16 patients who developed acute thrombocytopenia while taking either quinine or quinidine could be demonstrated readily with the 51Cr platelet lysis test and could also be detected by other methods employed.


Chronic lymphocytic leukemia: correlation of clinical course and therapeutic response with in vitro testing and morphology of lymphocytes. Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy. In vitro testing of CLL lymphocytes following exposure to X-ray, PHA, DMSO 2 hr at 43 degrees C, prednisolone, glutaminase, and asparaginase permitted a separation of patients into categories of normal and abnormal in vitro responses. A normal in vitro response predicted a good response to therapy but an abnormal in vitro response did not preclude a good response to therapy. Following therapy, normalization of abnormal EM morphology and in vitro response was seen in some patients. Most patients tested had decreased serum immunoglobulins and abnormal PHA responses. There was a high incidence of infections and second neoplasms. Immunologic deficits could not be correlated with variations in lymphocyte morphology or in vitro response.


Bloom's syndrome. IV. Sister-chromatid exchanges in lymphocytes. An abnormally great amount of exhange between both sister and nonsister-but-homologous chromatids is a highly characteristic feature of cultured blood lymphocytes from individuals with Bloom's syndrome. However, a population of lymphocytes which exhibit a normal amount of exchange can be detected in the blood of some individuals with this syndrome. This coexistence of cells with a greatly increased number of sister-chromatid exchanges and others with a normal number results in a phenotypic dimorphism, in apparent contradiction to the autosomal recessive mode of inheritance of the syndrome.


Inheritance of F cell frequency in heterocellular hereditary persistence of fetal hemoglobin: an example of allelic exclusion. Two kindreds are described in which F cell frequency is inherited. These families differ in ethnic origin, the mean quantity of HbF per F cell, and in G gamma: A gamma ratios. Heterozygotes have approximately 50% F cells while homozygotes have close to 100%. Semiquantitative single cell immunodiffusion assays establish that F cells contain all of the HbF found in heterozygotes. Our finding that the gene for this heterocellular form of hereditary persistence of fetal hemoglobin is expressed in only half the cells provides the first example of allelic exclusion known apart from immunoglobulin expression.


Maple syrup urine disease: branched-chain keto acid decarboxylation in fibroblasts as measured with amino acids and keto acids. Branched-chain keto acid decarboxylase activity in skin fibroblasts from control subjects and from patients with classical and variant forms of maple syrup urine disease (MSUD) was measured with leucine and alpha-ketoisocaproic acid. When the keto acid was used as substrate in high concentrations (more than 5 mM), the three groups overlapped extensively, even classical cases of MSUD exhibiting decarboxylase activity. With leucine as substrate, decarboxylase activity plateaued at about 1.5 mM, and the three groups could be clearly differentiated. Classical cases of MSUD had minimal or no decarboxylase activity.


Polymorphisms of the haptoglobin peptide chains in Pyrenean populations. This study has analyzed the haptoglobin genotype frequencies in over 900 samples from populations living on the Northern slopes of the Pyrenees. The results emphasize the importance of systematically determining the frequencies of the Hp1S, Hp1F, Hp2SS, Hp2FF, Hp2FS alleles. Hp1S was the predominant allele, the HpIS/Hp1 distribution varying between .5 and .69 as in most European populations. Hp2 alleles were observed in low frequency with differences in geographically distinct samples. Pyrenean populations in the western zones (Basques and Baronnies) were found to contain the Hp2FF allele while those in eastern regions, the Hp2SS allele. We have speculated that Hp2SS is as old as the Hp2FF, arising from southern Mediterranean areas, and suggest that Pyrenean groups have different origins.


Characterization of a variant of beta-hexosaminidase: "hexosaminidase Paris". A family (father and daughter) was found with a deficiency of hexosaminidase (HEX A and HEX B). Residual HEX A activity was about 30% of usual heterozygotes with very little HEX B activity. Thermostability of HEX A was decreased. No immunological cross reacting material was found for HEX A or B. The mechanism seems to be the production of abnormal, unstable beta subunits, which are still capable of combining with alpha subunits to form functional HEX A.


The origin and behavior of two isodicentric bisatellited chromosomes. Karyotyping revealed three cell lines in a boy with mental retardation and few other abnormalities. Thirty cells exhibited a normal karyotype, and 54 had an extra acrocentric chromosome of E group size with satellites on the long and short arms. The remaining 20 cells each had, in addition to the first marker (M1), a second tiny bisatellited chromosome (M2). C-banding demonstrated that both markers were dicentric. G-, C-, and Q-banding and satellite association data were consistent with the markers having originated from chromosome 15 material. We propose that M1 was formed from a meiotic breakage and a chromatid fusion in the proximal long arms of an acrocentric pair. This would have produced a symmetrical isodicentric chromosomes, plus one or two acentric fragments. M2 then could have resulted from a dicentric bridge-break-synthesis-reunion phenomenon. This model of abnormal meiotic exchange can be generalized to encompass the formation of other dicentric isochromosome cases of isochromosome X.


The battle over blood collection.

The battle over blood collection. The struggle for control of this nation's life-giving blood resources was, up until five years ago, largely a private affair between representative organizations of the blood collectors. The system that emerged from that struggle was declared unhealthy by several experts who complained that blood was too often unsafe or unavailable. Then in 1972 the government, predominantly the federal government, responded to public pressure and joined the fray. This Comment examines some legal, political, and policy aspects of the battle over blood collection--a battle from which no stable guiding force has yet evolved.


Comprehensive pharmaceutical services in an 85-bed hospital: a one-year evaluation. The economics of a comprehensive pharmaceutical service in a small hospital was evaluated. The pharmacy program includes total unit dose drug distribution, centralized compounding of intravenous admixtures, and clinical involvement. Data were collected for two fiscal years prior to the development of formal pharmaceutical services (FY 72-73 and FY 73-74), the fiscal year during the implementation phase (FY 74-75) and the fiscal year following full development (FY 75-76). The total cost of the pharmaceutical services for FY 75-76 was $5.66 per patient day, a 106% increase over the previous year. The revenue per patient day in FY 75-76 was $7.77, a 72% increase over FY 74-75. Inventory costs decreased during and after implementation of comprehensive pharmaceutical services. The evaluation emphasizes the need for assessing pharmacy programs as an integrated system representative of the service of pharmacy. The need for an equitable method of third party payment for pharmaceutical services is discussed.


Pharmacist's role in loss and grief.

Pharmacist's role in loss and grief. The role of the pharmacist in helping to guide the patient and his family through the grief and bereavement process of death is described. The somatic and psychological components of grief and the five psychological stages of dying--denial and isolation, anger, bargaining, depression, and acceptance--are discussed. The pharmacist's role is one of understanding, tolerance and empathy for the dying patient and his family.


Drug interference with the Schack and Waxler plasma theophylline assay. Drug-induced modification of the spectrophotometric theophylline plasma measurement was investigated in vitro using 14 drugs which coextract with theophylline and absorb ultraviolet light in the same wavelength region. Plasma samples spiked with 15 microng/ml theophylline and other potentially interfering drugs in therapeutic concentrations were analyzed according to the Schack and Waxler procedure. The absorbance of the alkalinized aqueous layer was read on a scanning spectrophotometer at 275 and 310 nm. Allopurinol, caffeine, phenobarbital, ampicillin and phenytoin did not appear to interfere with the measurement of theophylline. In contrast, furosemide, sulfathiazole, phenylbutazone, probenecid and theobromine produced potentially clinically significant false positive elevations of the theophylline plasma concentration. Warfarin, bishydroxycoumarin and salicylic acid produced an underestimation in the theophylline plasma concentration. The Schack and Waxler sectrophotometric method of measuring theophylline plasma concentration should be used with caution when patients are taking drugs which are weak acids which absorb in the 250-350 nm range.


Effect of NLRB rulings on collective bargaining by hospital pharmacists. The implications for hospital pharmacists of recent National Labor Relations Board (NLRB) rulings are discussed. The history of hospital coverage under federal labor laws is reviewed, including the removal of the exemption of nonprofit hospitals from the Taft-Hartley Act in 1974. Also discussed is the ruling of the NLRB in the case of Mercy Hospitals of Sacramento wherein appropriate bargaining units of hospital workers were defined. Finally, the question of exclusive bargaining units for hospital pharmacists, as addressed in NLRB rulings in the Kaiser Foundation Hospitals and San Jose Hospital and Medical Center cases, is reviewed. Apparently, the NLRB did not rule in favor of exclusive hospital pharmacist units primarily because of an insufficient history of such units. Although there are inconsistencies in the NLRB's rulings in Mercy Hospitals and San Jose, it is unlikely that the policy expressed in these cases will be changed in the near future.


Absolute bioavailability of oral theophylline. The absolute bioavailability of theophylline was investigated by comparing the areas under concentration-time curves for intravenous theophylline with a plain uncoated anhydrous theophylline tablet and a theophylline solution. Twenty asthmatic adults received approximately 7.5 mg/kg theophylline intravenously over 30 minutes; either seven days before or after the i.v. dose, 10 of these patients received tablets and the remainder solution in a similar dose. Blood samples were obtained at 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes and then every two hours for at least 12 hours. Theophylline concentration was measured in serum by high-pressure cation exchange chromatography. The fraction of the dose absorbed averaged 0.96 +/- 0.03 for the tablet while the value for the solution was 0.99 +/- 0.02. The time of peak absorption averaged 2 +/- 0.3 hours for the tablets and 1.4 +/- 0.3 hours for the solution. The maximum serum concentration attained was 15.3 +/- 0.7 microng/ml after a dose of 7.6 +/- 0.4 mg/kg of the tablet, and 14.6 +/- 0.6 microng/ml after a dose of 7.3 +/- 0.2 mg/kg of the solution. Absorption of the tested theophylline tablets and solution approached 100% of the available drug.


Principles of echocardiography.

Principles of echocardiography. Echocardiography is basically a diagnostic procedure whereby images of the heart are produced using ultrasound. It can be considered a natural means of sensing one's environment in that this basic technic is used by several animals as sonar. The manner in which the images are created is in many ways similar to light. With the standard M-mode examination one obtains a one-dimensional view of the heart whereby distance is plotted against time on a strip chart recorder. Cross-sectional or two-dimensional echocardiography plots distance against distance, and one more accurately recreates a spatially oriented heart on either movie film or videotape. All the availability information thus far indicates that echocardiography offers very little, if any, hazard to the patient.


Echocardiographic evaluation of patients with mitral stenosis. Since the introduction of ultrasound technics to study the heart, echocardiographic evaluation of the mitral valve has become the most sensitive and specific noninvasive method for diagnosing mitral stenosis. Identification of the anterior mitral leaflet and the reduction of its velocity of motion was the first clinical application of M-mode echocardiography. Although simultaneous visualization of both mitral leaflets aids in the diagnosis of mitral stenosis, quantitation was not achieved until real-time imaging systems were developed to produce cross-sectional images of the mitral orifice. Currently, M-mode echocardiography remains the technic of choice for routinely diagnosing mitral stenosis. It is also useful in confirming mitral stenosis when associated abnormalities, such as aortic regurgitation, are present. Mitral orifice area is best determined with cross-sectional (two-dimensional) imaging systems. This method correlates well with hemodynamic parameters. Both methods offer the clinician serial evaluation before and after operative intervention.


Echocardiographic identification of the mitral valve prolapse syndrome. The data presented herein would indicate that mitral valve prolapse may be represented by a variable spectrum of abnormalities on the echocardiogram. Utilizing all the abnormalities described, echographic evidence of mitral valve prolapse may be detected in most patients with this disorder. However, evidence of mitral valve prolapse may also be observed in a large contingent of asymptomatic patients without other clinical manifestations of cardiac disease. The biologic significance of these echographic abnormalities remains uncertain and constitutes an important area for future investigation.


Echocardiography of the aortic root.

Echocardiography of the aortic root. The anterior and posterior walls of the aortic root are recognized as a pair of parallel linear signals which move anteriorly in systole and posteriorly in diastole. Valve cusps appear as thin lines which move briskly toward the periphery of the aortic lumen in systole and coapt in the middle in diastole producing a box-like configuration. Cusp calcification results in the appearance of multiple, linear echoes within the aortic root. Mild aortic stenosis is characterized by lightly calcified leaflets whereas heavy calcification, which completely obscures cusp motion, signifies severe stenosis. Aortic aneurysms produce significant enlargement of the aortic root image; marked widening of the aortic walls indicates the presence of aortic root dissection, but there are important limitations and pitfalls in the diagnosis of this condition. A markedly eccentric diastolic cusp position within the aortic lumen resulting in asymmetric images of the leaflets in systole is the hallmark of a bicuspid aortic valve. An abrupt premature closure of the valve leaflets in early systole is typical of subaortic membranous stenosis. In tetralogy of Fallot the aortic root is dilated and overrides the ventricular septum.


Pulmonary valve echo motion in clinical practice. Examination of the pattern of pulmonary valve echo motion provides useful diagnostic information in a variety of clinical situations. This report describes the normal patterns and variations in pulmonary valve echo motion. It further discusses the applications and  limitations of M-mode and cross-sectional echocardiography in detecting obstruction to right ventricular outflow at both the valvular and infundibular level; the wide ranging effects of increases in pulmonary artery pressure on the pulmonary valve echogram; and alterations in right ventricular compliance and volume which may combine to produce diastolic opening of the pulmonary valve. It is emphasized that the thin pliable pulmonary leaflets move in response to local alterations in pressure and flow. The patterns of pulmonary valve echo motion, therefore, although not specific for any particular clinical disorder, may provide valuable, indirect information concerning local pressure and flow characteristics and, as such, may prove extremely helpful when applied to a specific clinical situation.


Echocardiography in valvular vegetations. Echocardiography represents the only noninvasive technic available for detecting vegetations. In fact, the technic is more sensitive in indentifying these lesions than even angiography. The invasive examination is only capable of detecting very large valvular vegetations. Although echocardiography frequently discloses no abnormalities in patients with clinically suspected or proved bacterial endocarditis, the presence of vegetations can be very helpful in the management of these patients. In addition to identifying vegetations echocardiography can be of great assistance in demonstrating disruption of the affected valve and in identifying that valve which might require surgical replacement.


Mechanisms of resistance to aminoglycosides. Bacterial resistance to aminoglycoside antibiotics occurs by a variety of mechanisms. In clinical situations the most common mechanism is plasmid-determined modification of the drug that leads to a block of transport of the antibiotic into the cell. Amikacin, a semisynthetic aminoglycoside, is effective against a number of resistant strains because it has fewer sites of modification.


Resistance to gentamicin, tobramycin and amikacin among clinical isolates of bacteria. Susceptibility to the administration of gentamicin, tobramycin and amikacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4,114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 microng discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 60%. Most of the gentamicin-resistant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnitude (most had minimal inhibitory concentrations (MIC's) between 31 and 125 microng/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.


Treatment of hospita-acquired infections with amikacin. Amikacin was used in the treatment of 56 serious gram-negative infections in 54 patients of whom 47 survived. In six of the seven nonsurvivors, the infections were under control at the time of death. The clinical isolates were multiple drug-resistant gram-negative organisms, with Proteus rettgeri being most common. Forty-five (80%) of these infections were nosocomial in origin, and the genitourinary tract was the source in 39 (70%). Complications directly related to amikacin therapy were few and suggested renal or otologic toxicity. In this series of patients, amikacin appeared to be of therapeutic benefit in the treatment of serious gram-negative infections.


Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin. A comparative study of the oto- and nephrotoxicity of amikacin and gentamicin was carried out prospectively. Twenty-six gentamicin-treated patients and 27 amikacin-treated patients were monitored for changes in auditory and renal function during and after therapy. Thirteen of those treated with gentamicin and 20 of those treated with amikacin underwent vestibular caloric testing which could be evaluated for evidence of toxicity. In four (15.4%) of the gentamicin-treated patients, nephrotoxicity developed; no such toxicity was seen in the amikacin-treated patients. This difference may have been due to a fortuitously higher incidence of pretreatment renal impairment in the gentamicin-treated group. In two gentamicin-treated patients (7.7%), ototoxicity developed (one auditory, one vestibular), and in two amikacin-treated patients (7.4%), auditory toxicity developed. Statistical analysis of oto- and nephrotoxicity and their risk factors was not attempted because of the small numbers of patients who could be evaluated. Additional patients are being studied.


Amikacin therapy for gram-negative septicemia. Amikacin was administered to 18 patients with gram-negative septicemia. Ten of the patients had blood culture isolates highly resistant to gentamicin; six of these patients had persistent bacteremia while receiving gentamicin alone or in combination with other agents. Fourteen of the 18 patients were cured with amikacin therapy and adjunctive measures. Nine of the 10 patients with gentamicin-resistant pathogens were cured. The occurrence of nephrotoxicity in four patients with elevated amikacin serum levels and serious underlying disease indicates the desirability of monitoring serum amikacin levels. Minor ototoxicity occurred in two patients and was associated with prolonged therapy and high serum amikacin levels. Amikacin is a highly effective agent for treating patients with gram-negative bacteremia; it is the agent of choice in the therapy of patients with suspected or documented gram-negative bacteremia caused by pathogens resistant to gentamicin and susceptible to amikacin.


Amikacin therapy of gram-negative bacteremia. Treatment with amikacin was evaluated in 15 patients with gram-negative bacteremia. The sources of sepsis were urinary tract (in six patients), abdomen (in five) and miscellaneous sites (in four). Sixteen bacterial pathogens were recovered, including three gentamicin-resistant organisms. All isolates were susceptible to amikacin. Eleven of the 14 patients who could be evaluated fulfilled the criteria for cure, including the three patients with gentamicin-resistant organisms. Three patients failed to respond to amikacin therapy. Monitoring untoward effects revealed eighth nerve toxicity in one patient and nephrotoxicity in one patient. These results indicate that amikacin is effective in the treatment of patients with gram-negative bacteremia, even when caused by gentamicin-resistant bacteria.


Review of 152 patients with bacteremias treated with amikacin. The efficacy of amikacin treatment of 152 patients with bacteremia was reviewed from case reports submitted by 53 investigators. Eighty-one per cent of these patients had a favorable outcome; 73% were cured and 8% partially cured. Analysis of the 29 treatment failures revealed that the majority (21) were in patients with either pneumonia, leukemia or mixed aerobic-anaerobic infections. Forty-five patients were infected with gentamicin-resistant organisms; 66% of these patients were cured following amikacin therapy, and 14% had a partial cure. These results indicate that amikacin is effective in the therapy of gram-negative bacteremia, even in  seriously ill patients with gentamicin-resistant pathogens.


Amikacin treatment of pulmonary infections involving gentamicin-resistant gram-negative bacilli. Twelve patients with pulmonary infections presumably involving gentamicin-resistant gram-negative bacilli were evaluated for their response to amikacin therapy. All patients had hospital-acquired infections for which they had been previously treated and were considered therapeutic failures with gentamicin or tobramycin. Assessment of response to amikacin therapy showed objective evidence of clinical improvement in 11. The gentamicin-resistant organism was eradicated in nine patients although, in the majority, other gram-negative bacilli persisted in respiratory tract secretions both during and after treatment. There was one clinical failure.


Amikacin in the treatment of gram-negative pneumonia. A clinical efficacy study of amikacin in the treatment of 15 adults with nonbacteremic, gram-negative bacillary pneumonia is presented. All patients had serious underlying illnesses (11 organic heart disease, five chronic obstructive pulmonary disease, one cancer); 11 had undergone major surgical procedures. All had required respiratory assistance during their hospitalization and all had recently received other antibiotics. Thirteen of 15 patients showed clinical improvement with amikacin therapy; the pathogen was also eradicated in 10 of the 13. The mean minimum inhibitory concentration of amikacin for the 17 isolated pathogens was 3.13 microng/ml. The mean peak serum concentration of amikacin was 17.7 microng/ml. No evidence of ototoxicity or nephrotoxicity was seen. Seventy-three case reports submitted to the manufacturer by multiple investigators of patients with gram-negative pneumonia, treated with amikacin, are also reviewed. All isolated pathogens were sensitive to both amikacin and gentamicin. Fifty-four (74%) of these patients showed improvement with amikacin therapy.


Pathogenic carrier rate in diabetes mellitus. Thirty patients with diabetes mellitus were compared in terms of carrier rate of four pathogens to a group of matched controls. The diabetics were found to have a significantly increased carrier rate (p less than 0.005). When the blood glucose level was used as an indicator of control an increased rate was found in those with the poorest control (p less than 0.0005). An increased carriage of Candida albicans might be attributed to hypovitaminosis A and its effect on mucous membranes and the skin. Ten percent of diabetics were carrying beta-hemolytic group A streptococci. In a future study these patients will be checked for persistence of these organisms as well as to see if the strains are of the nephritogenic type. A significantly increased carriage rate in diabetes of coagulase-positive Staphylococcus aureus was found. These findings suggest an additional risk factor in the outpatient diabetic population.


Scientific explanation and ecological validity: a reply to Brooks and Baumeister. There are two different goals a researcher might have in studying behavior of retarded persons. One is to gain a scientific understanding of low intelligence as a subcategory of human intellectual functioning. The other is to develop practical techniques for prediction, control, and remediation of retardation in daily life. Brooks and Baumeister (1977) have confused the two and have advocated methods suitable for practical application to answer questions about the nature of retardation. They have done a disservice to the field in disparaging basic research.


Ultrastructural observations in myopathy complicating Cushing's disease. The ultrastructural findings in a muscle biopsy of a patient with Cushing's disease associated with severe myopathy are described. They included pronounced mitochondrial damage, thickening and deep invaginations of the sarcolemmal basement membrane, and thickening of the basement membrane of the capillaries. In addition, the muscle fibers showed a marked degree of disarray and wide interfibrillar spaces, containing large numbers of vacuoles, which presented degenerated mitochondria. The similarity between these findings and the ultrastructural features of corticosteroid-induced myopathy is discussed.


Are we making a science of missing the point? Our basic point of contention with House concerns the form we ultimately expect our sceintific explanations of retarded behavior to take. It is our view that mental retardation, which is basically a social phenomenon, can be meaningfully understood only to the extent that ecological validity and other related issues are assigned prominence in our theories and experiments.


Chronic eosinophilic pneumonia: a report of four cases and a review of the literature. The clinical and radiological findings of four patients with chronic eosinophilic pneumonia are presented. This brings the total number of cases in the English literature to 27. A comparison of all 27 patients is given. The syndrome can readily be distinguished from other eosinophilic pneumonias. After appropriate evaluation, a therapeutic trial can often be initiated with corticosteroids without the necessity for histologic confirmation of the diagnosis.


Uremia with low serum creatinine-an entity produced by marked creatinine secretion. Two patients are presented who were uremic requiring dialysis despite steady state serum creatinine levels (Cr) of 4.0 and 4.4 mg percent. Their blood urea nitrogen/creatinine (BUN/Cr) ratios of 54 and 44 were shown to be due to excessive creatinine secretion and urea reabsorption. Evaluation of serum creatinine alone may occasionally give misleading information regarding the level of renal function. If clinical evidence of uremia is present while serum creatinine value is relatively low, measurement of glomerular filtration rate (GFR) by Na-iothalamate 125I (OIT) or inulin is essential.


Serum ferritin, free erythrocyte protoporphyrin, and urinary iron excretion in patients with iron disorders. Tests to evaluate body iron stores were compared in patients with iron deficiency and the anemia of chronic disease. The serum ferritin assay separated these disorders in 20 of 22 patients. One discrepancy was explained by the concomitant association of both disorders. From this study and review of literature a low serum ferritin level is a good indication for iron therapy. The serum ferritin assay is a clinically useful test in lieu of bone marrow estimation of body iron stores to detect patients with iron deficiency. Total iron binding capacity levels when high-normal or elevated are sometimes helpful as a screening test in separating iron deficiency from the anemia of chronic disorders. Free erythrocyte protoporphyrin values were elevated in both conditions but were higher in iron deficiency than in the anemia of chronic disorders with considerable overlap of values. Urinary iron excretion with deferoxamine was not helpful in separating these disorders but is a useful test to establish iron overload. An elevated serum ferritin level is usually found with disease of iron overload but serum iron levels, deferoxamine iron excretion tests, and liver biopsy for estimation of iron stores are still beneficial diagnostic aids.


Effects of the label "mentally retarded" on causal explanations for success and failure outcomes. Previous research has been inconclusive in demonstrating the effects of the label "mentally retarded" on the reactions and evaluations of others toward the labeled person. The present study derived predictions from attribution theory regarding the effects of the label on the perceptions of observers. Specifically, we hypothesized that the presence of the label would reduce the likelihood that observers would credit successful task outcomes to the labeled person's ability but enhance the likelihood that observers would credit unsuccessful task outcomes to the labeled person's ability. Such effects were not anticipated in the absence of the label. A factorial design varying Labels (mentally retarded us. no label), Task Outcomes (success v. failure), and Sex of Target Person was employed. Dependent variables measured observers' assessments of the causes of the target person's outcomes. The results strongly confirmed the hypothesis by showing that ability, effort, and task difficulty are all perceived differently for labeled than for nonlabeled target persons. The results were discussed in terms of implications for future research and proper use of the label "mentally retarded."


Hyperviscosity syndrome in a patient with systemic lupus erythematosus. The occurrence of hyperviscosity syndrome in a 22-year-old woman with systemic lupus erythematosus was reported. Ultracentrifuge study of her serum revealed the presence of intermediate complexes with sedimentation coefficients of 10.9S to 14.2S. The complexes were shown to consist of immunoglobulin G and immunoglobulin A and considered to be mainly responsible for the increased serum viscosity. This unusual protein abnormality responded remarkably well to the treatment with prednisolone.


The echocardiographic diagnosis of calcified mitral annulus. Echocardiograms were recorded in six patients with calcification of the mitral annulus. Echocardiographic sweep from the aorta to the left ventricular cavity revealed dense echoes, representing annulus calcification, posterior to the mitral valve. Characteristic calcium deposits in the region of the mitral annulus were detected on the chest roentgenogram of only a single subject. Cardiac fluoroscopy fluoroscopy demonstrated calcified mitral annulus in all patients. In one patient, coexisting calcified mitral annulus and proven pericardial effusion were diagnosed echocardiographically. It is concluded that the echocardiogram represents a useful noninvasive technic for the diagnosis of calcified mitral annulus.


Being imitated by an adult and the subsequent imitative behavior of retarded children. Institutionalized retarded subjects (N=57) were assigned to one of three experimental conditions during a simple three-choice task in which the subjects and the experimenter took turns feeding colored plastic "Cookie Monster." In the imitation condition, the experimenter imitated the subject's choice, and in the ninimtation condition, the experimenter avoided imitating the subject. Following imitation or nonimitation, the subject was given opportunities to imitate the experimenter. In the modeling only condition, the subject's choice always followed the experimenter's so that the subject always had the opportunity to imitate. Analysis of variance revealed a significant difference among the three conditions (p less than .008) in the subjects' tendency to imitate the experimenter. Paired comparisons between conditions showed that subjects in the imitation condition imitated significantly more (p less than .05) than subjects in either the nonimitation or modeling only condition. The nonimitation and modeling only conditions did not differ significantly. Theoretical and practical implications of the findings were discussed.


Effects of alterations in arterial pressure and heart rate on ST-segment elevation in a patient with acute myocardial infarction. This report describes a 70-year-old male with an anterior transmural myocardial infarction who showed major alterations in the magnitude of ST-segment elevation of his electrocardiogram, when an abrupt change of his heart rate (reduction) and blood pressure (increase) occurred when he reverted to normal sinus rhythm from atrial fibrillation. No concomitant change of other parameters of his clinical status was observed. This report stresses the significance of monitoring serially blood pressure, heart rate, and clinical symptomatology, in addition to electrocardiographic ST-segment elevations in patients with myocardial infarction, when therapeutic interventions aimed at reducing the infarct size are evaluated.


Performance of retarded adolescents and nonretarded children on the Tower of Hanoi Problem. Groups of retarded adolescents and nonretarded children, varying in MA were presented with 2-disk and 3-disk Tower of Hanoi puzzles, solutions to which require a certain amount of logical foresight. Nonretarded 8- to 11-year-old children performed at close to ceiling on the 2-disk task but had difficulty with the 3-disk task. Retarded groups with MAs ranging from 8 to 11 years performed no differently than nonretarded 6- and 7-year-old children. They had some difficulty on the 2-disk task, and very few reached criterion on the 3-risk task. They tended to preseverate in their errors and frequently resorted to game-rule viole perform many years below MA expectations on tasks requiring foresight and logic.


Aides' involvement in decision-making and the quality of care in institutional settings. Using two measures of the quality of care in institutional settings, we found much variance in the care provided within three institutional settings. Factors that might account for this variance were examined. Aides' perception of their involvement in certain areas of decision-making was shown to be of major importance in accounting for the variance in quality of care.


Temporal extrapolation of unimodal and multimodal stimulus sequences in retarded and nonretarded persons. Retarded adolescents, CA-matched nonretarded adolescents, and MA-matched nonretarded children attempted to match the repetition rate of 10-second stimulus sequences presented under four modality switching conditions and at two pusle frequencies. Error magnitudes were least for the CA-matched subjects and under the faster pulse rate increased from the no-switching to maximum-switching condition in all groups. Error increases from the no-switching to maximum-switching condition were preponderantly underestimations. No differences between groups were obtained for a switching condition in which the modality-sequence pattern was aperiodic. A hypothesis of longer psycholoical refractory periods in retarded adolescents was rejected in favor of one explaining their inferior performance on sequential enumeration and tracking tasks in terms of inefficient organizational abilities.


Communication style and effectiveness in homogeneous and heterogeneous dyads of retarded children. The channels, styles, and successfulness of communication used by retarded children when teaching a simple board game to a listener of similar or dissimilar age and ability to themselves were investigated. Forty children, half of high level and half of low level (means MAs=6.6 and 3.7 years, mean CAs-15.5 and 11.2 years, respectively) instructed a naive listener either at their own or at the other level, after they had been taught the game by the experimenter. Both high- and low-level speakers altered their channels and styles of communication to low-level listeners along the dimensions found by Shatz and Gelman (1973) with nonretarded children. However, the communication shifts, particularly those produced by high-level speakers, were ineffective in producing listener understanding. We concluded than communication-skills training for retarded children must be concentrated not only on the linguistic form, but also on the functional appropriateness of the children's utterances.


Reliability and validity of the Social and Prevocational Information Battery for mildly retarded individuals. The reliability and validity of the Social and Prevocational Information Battery (SPIB) for EMR individuals was evaluated with samples other than those on whom the battery was developed. Results substantiated initially reported reliability and validity indices and provided encouraging evidence  for the general appropriateness of the SPIB for use with mildly retarded adolescents and young adults.


Partial trisomy of chromosome 15.

Partial trisomy of chromosome 15. Chromosome analysis of a moderately mentally retarded female revealed a 47,XX,+G? karyotype. Giemsa-trypsin banding showed the extra chromosome to be a deleted chromosome 15 (47,XX,+15q-). This case points out the importance of cytogenetic studies in moderately retarded individuals without significant physical anomalies.


Plasma unconjugated estriol values in high-risk pregnancy. The usefulness of plasma estriol concentrations in the management of high-risk pregnancy is controversial. In this study, serial plasma unconjugated estriol (E3) concentrations determined by radioimmunoassay were evaluated in 321 patients with high-risk pregnancy for correlation with fetal and neonatal performance. A plasma E3 concentration of 4 ng. per milliliter or less in late pregnancy correlated significantly with low one-and five-minute Apgar scores and selected neonatal problems in pregnancies complicated by chronic hypertension and intrauterine growth retardation, with a similar trend for pregnancies complicated by moderate and severe pre-eclampsia. Most perinatal deaths in the study were associated with acute problems which began during labor and delivery, or fetal death occurred before early intervention was practical. Therefore, the perinatal mortality rate is not likely to be influenced by the use of E3 values, and the perinatal mortality rate is not a realistic measure of the usefulness of plasma E3 values in management of high-risk pregnancy. Low plasma E3 values were not always ominous, and for this reason it is suggested that clinical indications and the results of other tests for fetal-placental function be considered along with plasma E3 values in the selection of patients for early delivery to reduce the possibility of inappropriate intervention.


Pulmonary thromboembolism associated with gynecologic surgery and pregnancy. Pulmonary thromboembolism continues to be an infrequent but serious complication of gynecologic surgery and pregnancy. The record of each patient with such a complication treated in two community hospitals during the 10 year period to 1976 was examined in detail. An attempt was made to identify weaknesses in past management and suggest changes to improve future care. Embolism will continue to occur unexpectedly and be of such magnitude as to cause death before effective treatment. can be instituted. Patients at risk can often be identified and prophylactic anticoagulants and antibiotics are appropriate in selected cases. An understanding of the pathology of embolism of and principles of genital sepsis combined with vigorous treatment will save some patients who now would die. If the risks are appreciated, anticoagulants may be used in pregnant patients who are closely monitored. These patients must be alerted to the dangers of both embolism and the treatment.


Liver neoplasms and the oral contraceptives. For sixteen years (1954 to 1970) oral steroids had been used for contraception by millions of women. We were unable in this time span to find any cases of liver neoplasms in women using oral contraceptives. However, since 1970, there have been 138 cases reported in the English literature. We will add nine cases to this number, including an unusual case report. Evidence for the oral contraceptive as an etiologic agent in causing liver neoplasms is circumstantial but but nevertheless substantial. The literature is reviewed, and our case is presented. At present, the etiology of liver neoplasms is an enigma. Close clinical surveillance with an awareness of this potentially fatal pathologic entity is essential in women who have ingested oral contraceptives.


Autoimmune phenomena in ocular cicatricial pemphigoid. Twelve patients with various stages of ocular cicatricial pemphigoid were studied. Tear volumes measured by Schirmer tests and visual acuities were generally reduced in proportion to disease severity. Mannitol-positive staphylococcus was recovered from 67% (16/24) of the eyelids cultured. Immunoglobulins were bound to the basement membrane of clinically involved conjunctivae in 67% of the patients (8/12). Eighty percent (8/10) of the clinically normal conjunctivae had no immunoglobulins bound to the basement membrane or epithelium, further reinforcing the importance of tissue-fixed immunoglobulins in the pathogenesis of this condition. Four of eight patients with immunoglobulins bound to basement membrane also had C3 complement bound to basement membrane. Acute disease may be associated with the presence of complement in the conjunctiva. In addition, three of the eight patients with basement membrane staining, and three without, showed marked epithelial intercellular and intracellular staining for immunoglobulins. Indirect immunofluorescence of patients' sera showed no circulating antibodies to basement membrane, but three patients had circulating antibodies directed to the conjunctival epithelium in an intercellular or intracellular location. No significant association of ocular pemphigoid with other circulating autoantibodies. HLA aantigens, or abnormal serum immunoglobulin levels was realized.


Electroretinographic changes and choroidal defects in a case of central retinal artery occlusion. A 62-year-old white woman with hypertensive diabetes had central retinal artery occlusion of her right eye. Serial electroretinographic (ERG) studies demonstrated reversible changes in the scotopic components but permanent reduction of the photopic b-wave. Serial simultaneous fluorescein and indocyanine green angiographic studies demonstrated a perfusion defect in the choroid involving part of the macula which subsided after reopening the retinal circulation. Differential hypoxic susceptibility of the ERG photopic and scotopic b-waves was demonstrated, and changes in the patient's retinal tissue oxygenation were postulated on the basis of retinal and choroidal angiographic studies performed during and after central retinal artery occlusion to account for the observed changes in serial ERGS.


Ultrasonographic diagnosis of massive periretinal proliferation in eyes with opaque media (triangular retinal detachment). A triangular pattern of retinal detachment, as seen by B-scan ultrasonography in eyes with opaque media has been correlated with advanced massive periretinal proliferation (MPP). The ultrasonographic triangular configuration was created by a proliferative membrane that united detached retina anteriorly. Thirteen eyes with opaque media and a triangular retinal detachment by ultrasound had severe MPP at vitrectomy or enucleation. Twelve eyes with clear media with advanced MPP were also studies by B-scan ultrasonography and a triangular detachment could be demonstrated in each case. The finding of a triangular retinal detachment by B-scan ultrasonography in eyes with opaque media is diagnostic of advanced MPP. Eyes with this type of retinal detachment have a poor surgical prognosis even with modern vitrectomy techniques.


Optic neuropathy associated with vitamin B12 deficiency. A 17-year-old boy with vitamin B12 deficiency that occurred after a small bowel resection developed bilateral centrocecal scotomas during folic acid therapy and improved on therapy including vitamin B complex.


Amaurosis fugax caused by a prolapsed mitral valve leaflet in the midsystolic click, late systolic murmur syndrome. A 28-year-old man had recurrent episodes of amaurosis fugax of eight years' duration and had a congenital, late systolic mitral insufficiency murmur with the characteristics of the midsystolic click, late systolic murmur syndrome. The ophthalmologist must consider the clinical entity of the midsystolic click, late systolic murmur syndrome in the differential diagnosis of amaurosis fugax, especially when such attacks occur in young patients.


Neuroretinitis associated with herpes simplex encephalitis in an adult. A 48-year-old man who died of herpes simplex encephalitis had a bilateral papillitis at autopsy. Intranuclear inclusion bodies were especially numerous within the ganglion cells and inner nuclear layer of the macula and consisted of typical virions by electron microscopy. Contiguous spread from the brain to the eyes may have occurred via the optic nerves. Clinically, the disk and retinal changes were misinterpreted as being caused by papilledema. Papillitis should be included in the differential diagnosis of disk swelling in adults with suspected Herpesvirus hominis infection of the central nervous system.


Acute macular neuroretinopathy.

Acute macular neuroretinopathy. A 24-year-old white woman convalescing from a viral upper respiratory infection suddenly developed three positive scotomas around the fixation point in her left eye. The fundus had three corresponding lesions that appeared to be characteristic of acute macular neuroretinopathy. Situated in the fovea, subtle, reddish-brown, wedge- or tear-shaped lesions were best seen with the direct ophthalmoscope using red-free light. Visual acuity was 6/6 (20/20), and peripheral fields were normal. The patient's reproduction of the scotomas on an Amsler grid sheet mirrored the observed ophthalmoscopic findings. Fluorescein angiograms were normal. She had been taking oral contraceptives for many years. Although viral illness and oral contraceptives have been associated with acute macular neuroretinopathy, no etiology was proven, and no treatment is known. The patient remains symptomatic after a six-month follow-up.


The Westheimer function as an indicator of fixation locus. The dimensions of the Westheimer function are stable across populations and in time and vary with the eccentricity of fixation. The function is thus useful to assess whether an individual is fixing centrally and if not to estimate the degree of eccentricity of fixation. We identified both summation and inhibition-like regions in a 66-year-old woman with senile macular degeneration and estimated that the extent of eccentric fixation was approximately 4 degrees.


Cystoid macular edema occurring 13 years after cataract extraction. Thirteen years after cataract extraction, a patient complained of diminished visual acuity. In the interim visual acuity was 6/6 (20/20), or 6/7.5 (20/25+2). Fluorescein angiography demonstrated cystoid macular edema. Except for vitreous adherence to the inner surface of the cataract wound, no ocular cause for the macular edema was apparent.


Intrusion of scleral implant associated with conjunctival epithelial ingrowth. A 26-year-old boxer sustained a rhegmatogenous retinal detachment that was repaired successfully. Repeated blunt trauma caused a second retinal detachment two years later. Three attempts at repair by scleral buckling with diathermy and drainage of subretinal fluid were unsuccessful, and the eye was enucleated. Pathologic examination showed internal erosion of the intrascleral silicone implant into the vitreous compartment. Conjunctival-like epithelium lined the intrascleral bed of the implant and extended through the internal erosion onto intraocular structures, and this conjunctival epithelium was traced onto the external surface of the eye. Repeated dissection and applications of diathermy, combined with drainage of subretinal fluid, had weakened the sclera so that the silicone implant eroded internally and epithelium grew into the eye.


Microvascular injection studies in rubeosis iridis and neovascular glaucoma. Microvascular silicone injection, tissue clearing, and histologic examination were used to demonstrate the origin, distribution, and interconnections of newly formed iris and chamber angle blood vessels in four eyes with rubeosis iridis and neovascular glaucoma associated with diabetic retinopathy and central retinal vessel occlusion. The newly formed iris vessels that formed either a tight, evenly distributed (diabetic) or loose, irregularly distributed (central vessel occlusion) network in the iris originated from the normal iris arteries that were branches of either the major arterial circle or of the perforating branches of the anterior ciliary arteries, and drained into the normal iris and ciliary body veins and occasionally into the paralimbal episcleral veins. These newly formed iris vessels appeared to shunt intravascular fluid from arteries to veins. The newly formed anterior chamber angle vessels that formed tufts and arcades at the trabecular meshwork also originated from the roots of the iris arteries and the ciliary body arteries and connected with the peripheral neovascular iris network. In addition, the circumferentially running angle vessels that coursed within the trabecular meshwork branched into and coursed within a fibrosed Schlemm's canal and into two of its intrascleral collector channels. No open communication between these newly formed vessels and the Schlemm's canal-aqueous outflow system was seen.


Broad scleral buckle in the management of retinal detachments with giant tears. One of us (T.R.S.) operated on 24 patients with 26 retinal detachments caused by giant tears between 1969 and 1975 with the use of a broad silicone implant and diathermy. Minimum follow-up was six months. The technique included a scleral dissection extending at least three circumferential rows of diathermy posterior to the folded edge of the retinal flap, up onto the ora serrata, and two hours of the clock beyond each end of the tear. The retina was intentionally incarcerated on the buckle when subretinal fluid was drained. Sixty-nine percent of the cases were successfully reattached. If those patients with radial tears extending from the circumferential tears to the disk were excluded, the success rate rose to 75%. Seventeen percent of the successful reattachments required a second scleral buckle operation. Giant tears with radial tears extending to the disk, tears greater than 180 degrees, and immobile posteriorly everted flaps were poor prognostic signs. Thirty-five percent of the eyes with giant tears and a detachment had other holes or tears in the retina of that eye.


Successful lens removal in congenital corneolenticular adhesion (Peters' anomaly). A 6-month-old infant girl with congenital biomicroscopically visible corneolenticular adhesions underwent bilateral cataract aspiration and secondary capsulectomy resulting in bilaterally corrected visual acuity of 6/18 (20/60) at age 6 years.


Clinical evaluation of continuous-wear hydrophilic lenses. Twenty patients who had previously not worn contact lenses were fitted with a thin, continuous-wear hydrophilic contact lens in the right eye for 12 weeks. Seventeen patients completed the study and tolerated the lenses well. Some patients developed changes in corneal thickness, corneal curvature, and refraction, and some changes in visual acuity were reversed when the lens was removed. Many developed lens opacities that did not interfere with vision. We encountered no infections or corneal neovascularization in this study.


The effect of hyperthermia on aqueous humor dynamics in rabbits. Hyperthermia increased intraocular pressure (Po) by approximately 5 mm Hg in rabbit eyes. This increase was not associated with changes in plasma osmolarity, blood lactate, or pH. Episcleral venous pressure (Pv) decreased from a baseline of 11 +/- 1 mm Hg(mean +/- SEM) to 8 +/- 1 mm Hg after one hour of hyperthermia. Outflow facility (c) as measured by tonography remained unchanged. Aqueous humor flow [c(Po - Pv)] as estimated by tonography increased by about 126%. The elevation of intraocular pressure was not prevented by aspirin pretreatment nor altered by unilateral optic nerve transection.


Adenoid cystic carcinoma of the antrum and epiphora. Tearing was the initial symptom in two patients who subsequently developed a mass over the anterior lacrimal crest area caused by adenoid cystic carcinoma of the antrum. In a 76-year-old woman, a paranasal sinus X-ray film revealed an antral mass, and the histopathologic diagnosis was made by incisional biopsy. She refused further examination and treatment. In a 62-year-old woman, a paranasal sinus X-ray film and computed axial tomography examination revealed an antral mass. Epiphora caused by obstruction of the nasolacrimal sac was shown by dacryocystography. Bony destruction of the medial orbital floor was shown by paranasal sinus X-ray film, and confirmed at the time of initial biopsy. Orbital exenteration and radical maxillectomy and ethmoidectomy were performed, and the histopathologic diagnosis and primary site of the tumor were confirmed. There was no recurrence 24 months postoperatively.


Giant, mushroom-shaped osteoma of the orbit originating from the maxillary sinus. A 53-year-old woman had a six-month history of proptosis, pain, and decreased vision in the right eye. Skull X-ray films and polytomography demonstrated a giant, mushroom-shaped osteoma originating from the roof of the maxillary sinus and invading the orbit. The tumor was removed by a lateral orbital approach with prompt resolution of proptosis and pain, and recovery of normal vision and ocular motility. This patient is one of 34 patients with 38 paranasal sinus osteomas examined here in the last 25 years. Only six patients have had orbital symptoms or signs.


Ocular findings in I-cell disease (mucolipidosis type II). The ultrastructural study of the eyes in seven patients affected with I-cell disease (mucolipidosis type II) revealed important changes in the corneal, scleral, and uveal fibroblasts, while other cells were rarely involved. This explains the inconstant corneal clouding and the absence of ophthalmoscopic abnormalities clinically. At any moment of a patient's life, conjunctival biopsy specimens show characteristic alterations and allow the rapid and secure diagnosis of I-cell disease. This examination should be widely used in the screening of lysosomal diseases.


Thyroid function and the intraocular pressure response to topical corticosteroids. Baseline thyroxine, thyrotropin (TSH), and triiodothyronine (T3) resin uptake levels were measured in patients classified according to their topical intraocular response to corticosteroids. Results of thyroid studies were similar in patients with primary open-angle glaucoma and noncorticosteroid responsive (NN, intraocular pressure less than 20 mmHg after six weeks of topical 0.1% dexamethasone eyedrops) subjects. Primary open-angle glaucoma was not associated with the increased prevalence of low thyroid function values. The TSH suppression induced by oral dexamethasone was similar in NN subjects and patients with primary open-angle glaucoma. Patients with primary open-angle glaucoma did not demonstrate an increased glucocorticoid sensitivity as related to thyroid function. Thus, the adenohypophysial thyrotropic cell, the major site of dexamethasone inhibition of TSH secretion, does not appear to share the enhanced corticosteroid sensitivity of the eye, the hypothalamus, and the lymphocyte in patients with primary open-angle glaucoma.


Iris transillumination and variable expression in ectopia lentis et pupillae. Six children in three families showed variations of the rare genetic syndrome, ectopia lentis et pupillae. The siblings in two affected families demonstrated intermingling of simple lens ectopia with ectopia lentis et pupillae, suggesting that some types of simple ectopia lentis represent an incompletely expressed form of the full ectopia lentis et pupillae syndrome. Those patients with simple lens ectopia as well as those with ectopic lenses and pupils had striking transillumination of the iris periphery. Microphakia, cataract, and other anterior segment abnormalities were also observed.


Rapid development of band keratopathy in dry eyes. In three patients, calcium deposits rapidly developed within the superficial corneal stroma. All eyes had severe desiccation, a bacterial corneal ulcer, and frequent instillation of an artificial tear preparation. Calcium deposition within the ulcer base occurred within two to three weeks.


Experimental retinal neovascularization induced by intravitreal tumors. Adult rabbit retinal vessels underwent neovascularization in response to tumor implantation within the vitreous body. The neovascular response was presumably elicited by the tumor angiogenesis factor (TAF). The response of adult retinal vessels to an angiogenic stimulus raises the possibility that a similar substance may cause retinal neovascularization in humans, and that in normal conditions the vitreous may be able to suppress angiogenic activity.