Virilizing syndrome associated with an adrenal cortical adenoma secreting predominantly testosterone.

A 22 year old woman had virilization and mild Cushing's syndrome. Serum testosterone levels were high (3.2 ng/ml), urinary 17-ketosteroid levels slightly elevated (17.5 mg/d) and plasma cortisol at 16:00 hours normal (7.2 μg/dl). Basal level of cortisol secretion was normal but with evidence of autonomy. An abnormal adrenal scan led to an adrenal venogram showing a tumor image in the left adrenal gland. Selective adrenal venous catheterization indicated that the tumor was secreting testosterone and cortisol; left/right adrenal venous values were $\text{53.5}\text{3.7}$ ng/ml for testosterone and $\text{92.8}\text{13.6}$ μg/dl for cortisol. Testosterone levels did not rise with human chorionic gonadotropin (hCG). The basal serum level of Δ₄ androstenedione was at the upper limit of normal and of 17 α-hydroxyprogesterone high. The patient underwent surgical removal of a well circumscribed, 19 g left adrenal adenoma. Values for serum testosterone, DHEA-S and 17β-estradiol (E₂) decreased markedly postoperatively. The in vivo biochemical findings were corroborated in vitro by incubation of tumor tissue slices and nontumorous adrenal cortex. The tumor was capable of secreting testosterone, cortisol, DHEA and E₂, but the capacity was greatest for testosterone, DHEA and E₂. Analysis of tissue homogenates also revealed the presence of testosterone, cortisol, DHEA and E₂. The pattern of steroid production suggests partial 21-hydroxylase deficiency and enhanced 17β-reductase activity.     

Treatment of Clostridium difficile colitis and diarrhea with vancomycin

Toxigenic Clostridium difficile is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.     

Subacute myelomonocytic leukemia. Clinical, morphologic and ultrastructural studies of 10 cases

Clinical and morphologic features of subacute myelomonocytic leukemia are described in 10 patients. Clinical features included a prolonged symptomatic period prior to diagnosis, hepatosplenomegaly and hemorrhagic manifestations. Infections, especially in soft tissue areas, were common. Anemia, thrombocytopenia and leukocytosis were frequently seen. Peripheral blood monocytosis was found in 8 of 10 cases, and in all cases the monocytes appeared abnormal. Bone marrow aspirates were hypercellular and revealed monocytosis and megaloblastoid erythropoiesis. The clinical course was variable, and transition into acute myeloblastic or myelomonocytic leukemia was not observed. Death occurred primarily as a result of hemorrhage and/or sepsis between 3 months and 1 year after the onset of symptoms. The relationship between subacute myelomonocytic leukemia and other conditions designated as chronic monocytic leukemia, erythromonocytic leukemia and preleukemia is discussed.     

Thallium-201 versus technetium-99m pyrophosphate myocardial imaging in detection and evaluation of patients with acute myocardial infarction

Thallium-201 myocardial imaging is of value in the early detection and evaluation of patients with suspected acute infarction. The extent of a thallium defect in an initial myocardial image may have important prognostic value. Tomographic imaging techniques hold promise for increased diagnostic sensitivity and more accurate quantitation of both infarcted and residual viable myocardium. Thallium imaging may have a special value in characterizing patients with cardiogenic shock and in detecting patients at risk for subsequent infarction or death or both, before hospital discharge.

Approximately 95 percent of patients with transmural or nontransmural myocardial infarction can be detected with technetium-99m pyrophos-phate myocardial imaging if the imaging is performed 24 to 72 hours after the onset of symptoms. Pyrophosphate imaging has been useful in localizing the site and determining the extent of acute myocardial infarction. The “doughnut” pattern is associated with a relatively large incidence of subsequent congestive heart failure and death. However, the clinical utility of this information is limited because it is usually not available when it is most needed, on admission to the coronary care unit. Pyrophosphate imaging may have an important role in the evaluation of patients during the early follow-up period after hospital discharge from an episode of acute infarction. The finding of a persistently positive pyrophosphate image suggests a poor prognosis and is associated with a relatively large incidence of subsequent myocardial infarction and death.     

Radionuclide evaluation of postextrasystolic potentiation of left ventricular function induced by atrial and ventricular stimulation

Postextrasystolic potentiation of left ventricular function induced by ventricular and atrial stimulation was compared in 10 patients using radionuclide ventriculography. After insertion of pacing wires, a preliminary radionuclide ventriculogram was obtained and then ventricular and atrial trigeminy was induced in random order, each with identical R-R coupling intervals, each for 6 to 10 minutes. During the stimulation studies, radionuclide data were acquired in electrocardiographic gated list mode format. Left ventricular ejection fraction and relative end-diastolic and end-systolic volume changes were measured for each reformatted composite sinus, atrial and ventricular premature beat and potentiated beat. The volume changes were normalized to the count-based values obtained for the sinus beat of the appropriate study. Postextrasystolic potentiation induced by either ventricular or atrial stimulation was characterized by similar significant increases in left ventricular ejection fraction (mean ± standard deviation 7 ± 3 percent, p < 0.01 versus 7 ± 5 percent, p < 0.01; difference not significant [NS]) and decreases in relative end-systolic volume (?12 ± 12 percent, p < 0.01 versus ?12 ± 8 percent, p < 0.01; NS) but little change in relative end-diastolic volume (+5 ± 10 percent, NS versus +4 ± 7 percent, NS; NS). This was despite a longer compensatory pause (1,120 ± 220 versus 1,050 ± 190 ms, p < 0.01) after the ventricular premature beat. It is concluded that there is no difference in the postextrasystolic potentiation induced by atrial or ventricular premature stimulation.     

Totally implanted system for intravenous chemotherapy in patients with cancer

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphoma) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.     

Postural tachycardia syndrome: Reversal of sympathetic hyperresponsiveness and clinical improvement during sodium loading

A patient with disabling postural tachycardia without postural hypotension had symptoms that included palpitations, weakness, abdominal and leg pain, light-headedness, headache and diaphoresis that occurred only in the upright position. She was shown to have an enhanced sympathetic neural response to standing (exaggerated plasma norepinephrine response), and her cardiovascular responsiveness to released catecholamines was clearly intact. However, she was unable to maintain normal sodium balance and had a measurably reduced plasma volume while consuming normal amounts (120 mmol dally) of dietary sodium. Sodium loading (240 mmol ingested dally plus administration of fluorohydrocortisone, 0.1 mg daily) largely corrected the hemodynamic abnormalities, prevented postural symptoms and caused the compensatory sympathetic response to revert to normal.     

Epidemiology of antibiotic-associated colitis: Isolation of clostridium difficile from the hospital environment

Clostridium difficile is the most important cause of antibiotic-associated colitis. Using selective media, it was found that contamination with this organism was common in the environment of patients in the hospital with the disease. It was often found on floors, hoppers, toilets, bedding, mops, scales and furniture. This organism was also present on these items, but less often, in areas in which patients known to carry this hardy spore-forming organism had not been detected. Air, food and walls were negative. The organism was isolated from the hands and stools of asymptomatic hospital personnel. It was also found on surfaces in a patient's home. The importance of the various sources of the organism in its spread in the hospital is not known, and further studies are needed. It is suggested that enteric isolation precautions, and careful handwashing and cleansing of potentially contaminated surfaces and objects may be worthwhile when cases of antibiotic-associated colitis are identified.     

A heterozygote for Hb S beta, Hb C beta and Hb G Philadelphia beta in a family presenting evidence for heterogeneity of hemoglobin alpha chain loci.

A child heterozygous for the genes for hemoglobins S, C and G alpha Philadelphia presented with a clinical picture similar to sickle cell anemia. Her hemoglobin electrophoretic pattern contained three components with the mobilities of hemoglobins S (35 per cent), C (47 per cent) and a more slowly migrating hybrid G/C molecule (15 per cent). Seven relatives were heterozygous for Hb G beta and Hb S beta and five were heterozygous only for Hb G alpha. Among the latter, three had approximately 30 per cent and two had 40 per cent of Hb G. These proportions are consistent with the hypothesis that the American Negro genome contains two types of chromosomes bearing structural loci for alpha chains, some possessing one Hb alpha locus, others having two loci. Hb G alpha-Philadelphia presumably arose as a mutation on a chromosome with a single locus. Those heterozygotes having 30 per cent and 40 per cent Hb G presumably have two loci and only one locus, respectively, on the homologous chromosome.     

Atrioventricular block: natural history after permanent ventricular pacing

The preimplantation status, postimplantation morbidity and causes of late mortality were summarized for 246 patients who underwent pacing for atrioventricular (A-V) block at the University of Michigan for the 14 years from 1961 to 1974. The survival rate at 1, 5 and 10 years was 88, 61 and 49 percent, respectively. Risk of death was greatest among patients with antecedent ischemic or hypertensive heart disease or congestive heart failure in the period before pacemaker implantation, patients older than 74 years at initial implantation and those receiving a pacemaker before 1965. Forty-two percent of the 109 deaths were related to apparent progression of underlying cardiac disease. Pacing system malfunction was a contributing documented cause of only 3 deaths. Even with permanent pacemaker implantation, patients with A-V block have a higher age-specific mortality rate than the general U.S. population. Survival improved steadily over the period of study. This change is attributed to apparent improvements in treatment of cardiovascular disease including more effective treatment of congestive heart failure and valve replacement for selected patients as well as elimination of immediate postoperative mortality.     

Congenital stenosis of the pulmonic and tricuspid valves. Clinical, hemodynamic and angiographic observations in a 20 year old woman

Patients with congenital stenosis of the tricuspid and pulmonic valves are rare, indeed, and are expected to have underdeveloped right ventricles. The three obstructions in series, namely, tricuspid orifice, right ventricular inflow and right ventricular outflow typically result in symptomatic, cyanotic infants or young children with right to left shunts at atrial level. We present unique clinical, hemodynamic and angiographic information on a 20 year old acynotic, virtually asymptomatic woman with normally formed right ventricle and congenital stenosis of the tricuspid and pulmonic valves.     

Automatic computer processing of digital 2-dimensional echocardiograms

Quantitative studies of left ventricular function using 2-dimensional echocardiography have been limited because of a lack of computerized methods to automatically analyze the echocardiographic images. Previous computer efforts have been directed at digitizing the video output of the 2-D echocardiogram, but this digitizing method has significant limitations. A direct digitization method that produces improvement in signal-to-noise ratio and, subsequently, improved automatic detection of endocardial and epicardial borders, was developed. With definition of these edges, left ventricular global and regional analysis is possible frame by frame so that dynamic changes in cardiac function may be assessed throughout the cardiac cycle. Further technologic advances in 2-D echocardiographic acquisition and image processing should allow computer processing of 2-D echocardiographic data in real time.     

Evolution of antimicrobial resistance and nosocomial infection: Lessons from the vanderbilt experience

The development of antimicrobial resistance by bacteria has had profound effects on the clinical use of antibiotics, especially in hospital-acquired infections. In 1973, a large outbreak of nosocomial infections due to Serratia marcescens began at the Vanderbilt University medical complex, a major characteristic of which was high-level resistance to gentamicin and carbenicillin. Investigation of the outbreak and subsequent in vitro studies have shown that the evolution and epidemiology of this high-level resistance operated at three levels of organizations: (1)dissemination of individual strains, (2) dissemination of a plasmid among different strains and (3) movement of a discrete genetic element, or transposon, between plasmids. The investigations of this outbreak and other studies reviewed support the concept that resistant strains can evoke as a result of R-plasmid exchange within the hospital environment, providing an opportunity for control of this exchange can be interrupted.     

Spontaneous changes in thallium-201 myocardial perfusion imaging after myocardial infarction

To examine regional myocardial perfusion after myocardial infarction, 26 patients underwent exercise electrocardiographic testing with thallium-201 myocardial perfusion imaging 3 weeks and 3 months after infarction. At 3 weeks, 9 of 26 patients (35%) had myocardial ischemia by exercise electrocardiographic testing, whereas 18 of 26 (69%) had ischemia by thallium-201 imaging. The thallium-201 scintigrams were scored by dividing each image, in 3 views, into 5 segments, using a 5-point scoring scheme. The exercise thallium-201 score was 44.3 ± 1.2 and increased to 47.3 ± 1.2 in the redistribution study (p < 0.001). Three months after infarction, although there was a significantly greater rate-pressure product which would predict a larger ischemic defect and a decrease in the stress thallium-201 score, the stress score was improved (48.3 ± 1.1, p < 0.001). The redistribution score was similar, that is, 48.9 ± 1.0. The improvement in thallium-201 myocardial perfusion was associated with a loss of stress-induced ischemia in 8 patients (30%). These results indicate that spontaneous improvements in thallium-201 myocardial perfusion imaging may occur after myocardial infarction.     

Noninvasive quantification of jeopardized myocardial mass in dogs using 2-dimensional echocardiography and thallium-201 tomography

The evaluation of jeopardized myocardial mass is important in defining the effect of interventions during myocardial infarction. To quantitate the in vivo mass at risk, 2-dimensional echocardiography (2-D echo) and thallium-201 single-photon emission computed tomography (SPECT) was performed in 10 closed-chest dogs after circumflex coronary artery occlusion. The 2-D images were manually digitized to compute left ventricular (LV) mass using a modified Simpson's rule algorithm. This measure of LV mass correlated well with the actual LV mass (r = 0.97). Perfused myocardial mass was estimated from thallium SPECT images 4 hours after occlusion using a region-growing algorithm. After the dogs were killed, the jeopardized mass was outlined using a dual perfusion staining technique using triphenyltetrazolium chloride and Evans blue dye. The actual perfused mass was well estimated by the thallium images (r = 0.96). The noninvasively determined mass at risk was calculated as: 2-D mass — thallium SPECT mass, and correlated well with the pathologically determined mass at risk (r = 0.91). Thus, the jeopardized mass may be determined noninvasively by using 2-D echo and thallium-201 tomography. This approach may provide further information regarding the effect of intervention therapy on jeopardized myocardium.     

Rate-dependent effects of intravenous lidocaine, procainamide and amiodarone on intraventricular conduction

In this study, the duration of the QRS complex during ventricular pacing was used as an index of intraventricular conduction to quantitate the rate-dependent effects of intravenous lidocaine, procainamide and amiodarone. Right ventricular apical pacing (15 to 20 beats) was performed at cycle lengths of 600, 500, 400, 350, 300, 275 and 250 ms, before and 5 minutes after the intravenous administration of lidocaine in 11 patients (serum level 3.2 +/- 0.8 micrograms/ml [mean +/- SD] ), procainamide in 14 patients (serum level 8.2 +/- 1.9 micrograms/ml) and amiodarone in 12 patients (serum level 3.9 +/- 1.2 micrograms/ml). Electrocardiographic recordings were made at a paper speed of 150 mm/s. QRS duration was measured in a blinded fashion, with reproducibility within 5%. In the control state, QRS duration was the same at all paced cycle lengths. After lidocaine, procainamide and amiodarone administration, the shortest paced cycle length with complete ventricular capture was 250 +/- 0, 275 +/- 38 and 264 +/- 20 ms, respectively. At a paced cycle length of 600 ms, the increase in QRS duration compared with the control state was 1 +/- 2% with lidocaine (p greater than 0.05), 21 +/- 7% with procainamide (p less than 0.001) and 6 +/- 6% with amiodarone (p less than 0.05). At the shortest paced cycle length with complete capture, the increase in QRS duration compared with the control state was 20 +/- 6% with lidocaine (p less than 0.001), 42 +/- 11% with procainamide (p less than 0.001) and 26 +/- 4% with amiodarone (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytomegalovirus encephalitis associated with thymoma and immunoglobulin deficiency.

The clinical and immunologic findings in an elderly woman with thymoma and immunoglobulin deficiency in whom cytomegalovirus (CMV) encephalitis developed are described. The patient had absent serum immunoglobulins and no circulating immunoglobulin-bearing lymphocytes. Complement receptor-bearing lymphocytes were present in the peripheral blood, and circulating T lymphocyte numbers were within normal limits. She was anergic to a battery of skin test antigens, and her lymphocytes in vitro showed a selective unresponsiveness to CMV antigen while responding normally to phytohemagglutinin and streptokinase. The course of the encephalitis was progressive with quadriplegia, aphasia and coma developing within six months of onset of symptoms. This is the fifth reported case documenting an association between CMV infection and the syndrome of thymoma with immunoglobulin deficiency, but the first report of fatal CMV encephalitis in a patient with thymoma and immunoglobulin deficiency.     

Evaluation of left ventricular function in patients with sickle cell anemia

The echocardiographic measurements of cardiac chamber dimension, ejection phase indices of left ventricular function and the systolic time intervals of 23 adult patients with sickle cell anemia were compared to those of normal control subjects. Patients with sickle cell anemia had a significantly greater mean left ventricular systolic dimension index, left ventricular diastolic dimension index, left ventricular mass, stroke volume index, interventricular septal width, aortic root index and left atrial index. No significant differences were noted between the mean velocity of circumferential fiber shortening, ejection fraction or systolic time intervals. The anemic population was divided into two groups; one consisting of patients less than 30 years old and the other of patients over 30 years old. There were no significant differences between the ventricular dimensions, velocity of circumferential fiber shortening, ejection fraction and systolic time intervals of the two groups. These data indicate that the chronic volume overload of sickle cell anemia is well tolerated without development of left ventricular dysfunction.     

"Optimal" left ventricular filling pressure during nitroprusside infusion for congestive heart failure

On the basis of preload manipulations, an optimal left ventricular filling pressure of 14 to 18 mm Hg has been suggested for patients with left ventricular failure. Since afterload reduction results in increased cardiac output in heart failure, the hypothesis that left ventricular filling pressure could be reduced to normal by nitroprusside without compromising cardiac output was tested in 15 patients with acutely decompensated chronic congestive heart failure. Cardiac index was measured after each 4 to 6 mm Hg decrease in pulmonary wedge pressure until the latter fell below 14 mm Hg (Group I, nine patients) or until systolic arterial pressure reached 90 mm Hg during nitroprusside infusion (Group II, six patients). In Group I, pulmonary wedge pressure fell in significant decrements (p < 0.001) from 28 ± 4 (SD) to 24 ± 3, 17 ± 2, and 11 ± 2 mm Hg during nitroprusside infusion. Cardiac index rose in significant increments (p < 0.05) from 2.5 ± 0.8 to 2.8 ± 0.6, 3.3 ± 0.7, and 3.7 ± 1.1 liter/minute/m² with each increase in nitroprusside dosage. Mean arterial pressure fell during nitroprusside infusion from 97 ± 16 to 70 ± 8 mm Hg (p < 0.001) without any change in heart rate. In Group II, directionally identical changes in hemodynamics were observed during nitroprusside infusion; the highest cardiac index occurred at the lowest pulmonary wedge pressure attained, and no side effects were observed despite the fall in systolic arterial pressure to 90 mm Hg. Thus, reduction of left ventricular filling pressure to within the normal range by nitroprusside infusion in patients with chronic left ventricular failure can raise cardiac output beyond levels observed at left ventricular filling pressures of 14 to 18 mm Hg. Normalization of filling pressure may improve subendocardial coronary perfusion, and invasive monitoring of filling pressure during nitroprusside infusion may not be routinely required.