Pure gonadal dysgenesis. Studies of in vitro androgen metabolism

In the syndrome of pure gonadal dysgenesis, clitoromegaly is frequently present even when there are no other manifestations of androgen excess. A few cases have been reported with marked virilism, and the source of the androgen excess has been shown to be the streak gonads. Although the streak gonads contain several cell types, the lutein-Leydig cells have been theorized to be a source of testosterone synthesis. We report a case of pure gonadal dysgenesis with clitoromegaly in which pure nests of the lutein-Leydig cells were obtained from a gonadoblastoma and in which the conversion of ¹⁴C-androstenedione to ¹⁴C-testosterone by these cells was compared with that in an area of the gonad that contained no lutein-Leydig cells (germinoma). The data suggest that the lutein-Leydig cells contain 17-hydroxysteroid oxidoreductase and thus are capable of converting androstenedione to testosterone. The lutein-Leydig cells demonstrated a tenfold greater conversion of ¹⁴C-androstenedione to ¹⁴C-testosterone than the area that contained no lutein-Leydig cells. Thus, the lutein-Leydig cells are a potential source of gonadal testosterone in this patient.     

Intestinal anisakiasis. First case report from North America.

The first case of intestinal anisakiasis in North America is described. This parasitic disease is recognized as a public health hazard in Japan and Europe. Man becomes infected with a larval form of the nematode Anisakis by consuming raw or undercooked fish containing the parasite. Typically, patients present with acute abdominal syndromes. Clinical and reontgenographic features may cause confusion with regional enteritis. Histologically, a striking oesinophilic granulomatous reaction occurs. Anisakiasis is most effectively prevented by discouraging the consumption of raw fish.     

Diffuse pulmonary hemorrhage and rapidly progressive renal failure. An uncommon presentation of Wegener's granulomatosis.

A 57 year old woman presented with rapidly progressive renal failure and diffuse pulmonary hemorrhage and life-threatening respiratory failure promptly developed; these conditions resolved after bilateral nephrectomy. Renal pathology revealed rapidly progressive glomerulonephritis and vasculitis with granular deposition of immunoglobulin on immunofluorescent staining. One year later, multiple nodular cavitating pulmonary infilrates developed, and lung biopsy was diagnostic of Wegener's granulomatosis. Therapy with cyclophosphamide resulted in resolution of the pulmonary lesions. Diffuse pulmonary hemorrhage and rapidly developing renal failure mimicking Goodpasture's syndrome was the initial manifestation of Wegener's granulomatosis in this patient.     

Cardiac hypertrophy: Useful adaptation or pathologic process?

An extensive body of evidence supports the concept that cardiac hypertrophy and normal cardiac growth develop in response to increased hemodynamic loading and abnormal systolic and diastolic stresses at the myocardial fiber level. The pattern of hypertrophy reflects the nature of the inciting stress. Experimental studies indicate that if the stress is moderate, gradually applied, and the animal young and healthy, physiologic hypertrophy of muscle with normal contractility develops. In this circumstance, cardiac hypertrophy may be regarded as a useful adaptation to increased hemodynamic loading. When the inciting stress is severe, abruptly applied, or the animal old or debilitated, pathologic hypertrophy develops: in this circumstance, the cardiac muscle produced is abnormal and exhibits depressed contractility. Of particular clinical relevance is the intermediate situation which seems to develop in many patients with chronic left ventricular pressure-overload and perhaps also in left ventricular volume-overload. In this situation, chronic left ventricular pressure or volume overload is initially matched by adequate hypertrophy in the appropriate pattern. Eventually, in some patients, hypertrophy fails to keep pace with the hemodynamic overload so that a systolic stress imbalance occurs at the myocardial fiber level and left ventricular pump failure ensues. If this situation persists uncorrected, it is possible that the increasingly high wall stresses will convert physiologic to pathologic hypertrophy. The task of the clinician is to identify this intermediate stage and to correct the abnormal hemodynamic loading before the transition to pathologic hypertrophy becomes complete.     

Correction of infantile agranulocytosis (Kostmann's syndrome) by allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation has been unsuccessful as therapy for genetically determined bone marrow disorders. In patients prepared for transplantation with drugs alone long-term hematopoietic engraftment is not achieved due to the overgrowth of the infused donor bone marrow cells by residual recipient hematopoietic stem cells. Utilizing a combination of total body irradiation and antihuman thymocyte serum, the successful eradication of the abnormal hematopoietic stem cells of patients with the Wiskott-Aldrich syndrome and now infantile agranulocytosis has been achieved. Following preparation with total body irradiation and antihuman thymocyte serum a 20 month old patient with infantile agranulocytosis has complete donor hematopoietic and lymphoid engraftment one year after a histocompatible allogeneic bone marrow transplant. Prior to transplantation, this patient had no circulating or bone marrow granulocytes; following transplantation he has normal numbers of circulating granulocytes with normal in vivo and in vitro function. This therapeutic result demonstrates that genetic disorders of myeloid function can be corrected by allogeneic bone marrow transplantation following preparation with total body irradiation and antihuman thymocyte serum, and suggests that infantile agranulocytosis is due to an intrinsic defect of the pluripotent hematopoietic stem cell and not to a micro-environmental defect.     

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure: A physiologic assessment

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H₂O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.     

End-systolic volume as a predictor of postoperative left ventricular performance in volume overload from valvular regurgitation

Although over-all cardiac performance may remain normal in patients with left ventricular volume overload from valvular regurgitation, impairment of myocardial function may occur and remain undetected by currently accepted methods of assessing ventricular performance. Since end-systolic volume reflects myocardial contractile function yet is independent of preload, we assessed preoperative end-systolic volume as a measure of myocardial function in 41 patients with aortic regurgitation, mitral regurgitation or both. Preoperative end-systolic volume was compared to postoperative left ventricular performance as measured by postoperative echocardiographic per cent dimension change (% ΔD) and New York Heart Association class. Preoperative end-systolic volume correlated well with postoperative left ventricular performance in patients with aortic regurgitation (r = 0.77) or mitral regurgitation (r = 0.73). Much poorer correlations existed for preoperative ejection fraction, enddiastolic volume or left ventricular end-diastolic pressure. Preoperative end-systolic volume also predicted patients at high risk for perioperative cardiac death, with all such cardiac deaths occurring in patients with an end-systolic volume >60 cc/m². Again, both preoperative ejection fraction and end-diastolic volume were less precise predictors of surgical outcome. Patients with aortic regurgitation appeared to tolerate a larger end-systolic volume better than those with mitral regurgitation.End-systolic volume is an easily determinable parameter of left ventricular function which is independent of the abnormal preload that occurs in mitral regurgitation and aortic regurgitation and appears to provide a measure for the onset of myocardial dysfunction in patients with these lesions. Whether this myocardial dysfunction is due to a depressed inotropic state of individual sarcomeres, a stress-shortening imbalance or to other factors is unknown, but its presence has major prognostic importance.     

Small airway disease. An assessment of the tests of peripheral airway function

We measured specific conductance (SGa), 1 second forced expiratory volumes (FEV₁), maximum mid-expiratory flow rates (MMF) lung volumes, closing volumes (CV), static (Cst) and dynamic compliance (Cdyn), and resting gas exchange in 53 smokers in order to determine the relative yields and the interrelationships of the various tests for peripheral airway dysfunction. Small airway disease was considered to be present if values for Cst, FEV₁ and SGa were normal at the same time that values for CV, MMF, Cdyn or residual volume (RV) were abnormal. We found that Cdyn was abnormal more often (100 per cent) than either MMF (72 per cent), CV (55 per cent) or RV (47 per cent). Abnormalities of RV and CV were highly correlated.When we compared the over-all pulmonary function of the patients with depressed MMF with those with high CV, we found that the mechanism producing the former also affected SGa, FEV₁, Cst and perhaps RV, but not CV. Conversely, the mechanism that caused an increase in CV tended to influence RV, gas exchange and the lower part of the static pressure volume curve, but not the other variables. To account for these differences we postulate that the combination of frequency dependent Cdyn with a low MMF or a high CV may each represent the end results of different pathologic processes within the lung or, alternatively, the effect of a similar process working at different sites.     

Nonenzymatic glycosylation of protein: Relevance to diabetes

Glucose can react nonenzymatically with proteins to form stable covalent linkages. The most abundant minor hemoglobin component in human red cells is hemoglobin A_Ic: glucose is attached to the N-terminal amino group of the β chain by a ketoamine linkage. Hemoglobin A_Ic is increased two to threefold in the red cells of diabetic patients. It is formed slowly and continuously throughout the 120-day lifespan of the red cell. Measurement of hemoglobin A_Ic provides an index of average blood glucose levels over the preceding two or three months. Thus, hemoglobin A_Ic has proved to be useful in assessing diabetic control and, perhaps, in screening people for diabetes. Many other proteins, such as lens crystallins, collagen and proteins in serum and in red cell membrane, are modified by nonenzymatic glycosylation. This structural alteration may lead to impaired protein function and, perhaps, contribute to the long-term complications of diabetes.     

Listeriosis in immunosuppressed patients: A cluster of eight cases

Bacteremia due to Listeria monocytogenes developed in eight patients who were receiving immunosuppressive medications during a 15 month period at one hospital. Seven survived. Meningitis was documented in only the four who received kidney transplants. Their neurologic signs were minimal, indicating a need to treat any immunosuppressed patient with Listeria bacteremia for meningitis.During this period the incidence of Listeria bacteremia in immunosuppressed patients greatly exceeded that previously observed in this hospital or reported elsewhere, but the incidence of infection with other opportunistic agents was not increased. As with previously described Listeria outbreaks in nonimmunosuppressed patients, no source or mechanism of spread could be identified. Thus, disease due to L. monocytogenes may occur focally among immunosuppressed populations, a pattern which also appears to be emerging for other opportunistic agents. A patient's exposure to different opportunistic agents may be as important as the kind of immunosuppressive therapy he receives in determining which opportunistic infection he will acquire or even whether any infection will occur.     

Idiopathic ventricular tachycardia. An intracardiac electrical, hemodynamic and angiographic assessment of six patients.

Six patients with idiopathic paroxysmal ventricular tachycardia were investigated by external electrocardiography, intracardiac electrography and pacing, exercise testing, cardiac catheterization and coronary angiography. All had normal hemodynamics and coronary arteries. His bundle electrography proved ventricular origin in five; one had no paroxysmal ventricular tachycardia during His bundle electrography. Treatment with diphenylhydantoin, 4.2 to 8.0 mg/kg/day, and propranolol, 0.8 to 2.7 mg/kg/day, appeared effective, well tolerated therapy in three, and procainamide and propranolol in one requiring medical treatment. Abstinence from tobacco and coffee abolished paroxysmal ventricular tachycardia in one of two who required no medication. The other has no recurrence of paroxysmal ventricular tachycardia since study.     

Persistent empyema,bacteremia and death

Although oral nitrates are widely used as therapy for patients with congestive heart failure, their effectiveness in increasing cardiac output is highly variable. In order to identify predictors of outcome, we studied the effects of erithrityl tetranitrate (ETN) on preload, afterload and cardiac output in 15 patients with chronic congestive heart failure and mitral or aortic insufficiency who were undergoing diagnostic cardiac catheterization. There were significant reductions In right atrial, pulmonary capillary wedge and mean arterial pressures in nearly all patients. Augmentation in cardiac output by ≥ 10 per cent occurred in eight patients (responders), whereas no change (or decline) occurred in seven patients (nonresponders). The level of peripheral vasoconstriction, as reflected by resting systemic vascular resistance was significantly higher for responders than for nonresponders (2,602 ± 251 versus 1,744 ± 193 dynes-sec-cm^?5, p < 0.02). Furthermore, a significant reduction in systemic resistance occurred only in responders, and the decline was a linear function of resting resistance (r = 0.93). Thus, although reductions in arterial pressure, and left and right ventricular filling pressures are a constant result of nitrate therapy, significant augmentation in forward cardiac output is likely only in those patients with the most intense resting peripheral vasoconstriction. The concept of afterload mismatch and preload reserve best explains the variable effects of nitrates in congestive heart failure.     

Cutaneous lesions in disseminated candidiasis mimicking ecthyma gangrenosum

Cutaneous nodules are recognized as a manifestation of disseminated candidiasis. We describe skin lesions clinically identical to ecthyma gangrenosum that, on microscopic examination, were due to Candida emboli rather than Pseudomonas sepsis.Thus, the appearance of necrotic pustules and ulcerative plaques in the immunocompromised patient would raise the possibility of Candida as well as Pseudomonas sepsis, and illustrates the diagnostic importance of skin biopsy in such cases.     

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.