Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Münster study.

The incidence of atherosclerotic coronary artery disease (CAD) was assessed in 4,559 male participants (aged 40 to 64 years) from the Prospective Cardiovascular Münster study, over a 6-year follow-up period. During this time, 186 study participants developed atherosclerotic CAD (134 definite nonfatal myocardial infarctions and 52 definite atherosclerotic CAD deaths including 21 sudden cardiac deaths and 31 fatal myocardial infarctions). Univariate analysis revealed a significant association between the incidence of atherosclerotic CAD and high-density lipoprotein (HDL) cholesterol (p less than 0.001) and triglycerides (p less than 0.001). The relation to HDL cholesterol remained after adjustment for other risk factors. By contrast, the relation between the incidence of atherosclerotic CAD and triglycerides disappeared if, in a multivariate analysis by means of a multiple logistic function, cholesterol or HDL cholesterol were taken into account. However, the data suggested that hypertriglyceridemia is a powerful additional coronary risk factor, when excessive triglycerides coincide with a high ratio of plasma low-density lipoprotein cholesterol to HDL cholesterol (greater than 5.0). Even though the prevalence of this subgroup was only 4.3%, it included a quarter of all atherosclerotic CAD events observed.


The case for unstable angina pectoris as a primary end point in primary prevention studies.

Coronary artery disease (CAD) primary end point definitions used in previous prevention trials are reviewed, as well as trends over time for CAD mortality, incidence and hospital discharges to see if new primary end points should be considered. CAD mortality has shown a dramatic decline in the U.S. in the last 20 years, whereas the decrease in the incidence of acute myocardial infarction (AMI) is less consistent. The decline in CAD incidence and mortality has been attributed to changes in lifestyle and increased medical/surgical intervention. Hospital discharge rates for CAD have risen during the past decade. In addition, although the rate of discharge for AMI appears to have stabilized, the rates for angina, and more dramatically for unstable angina, have increased. Unstable angina made up 4% of CAD discharges in 1980, and increased to 25% of CAD discharges in 1989. Because of these trends, future trials that rely solely on AMI as a primary end point will not reflect the actual experience with CAD presentation in the U.S. Given the greater availability of methods to diagnose unstable angina more accurately, and because of its high risk pathology, it is concluded that unstable angina should receive serious consideration as a primary end point in future primary prevention trials.


Asymptomatic Cardiac Ischemia Pilot study (ACIP)

Ischemia can lead to myocardial necrosis, arrhythmias and death. Current practice suggests that asymptomatic or silent myocardial ischemia be treated as though it were symptomatic ischemia. This practice is associated with a growing trend of more frequent use of electrocardiographic monitoring, more complex therapeutic drug regimens and more frequent use of revascularization. However, there is no adequate study of the efficacy and safety of alternative therapeutic approaches to the treatment of asymptomatic myocardial ischemia. Therefore, the National Heart, Lung, and Blood Institute has planned the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. The ACIP study is a multicenter international pilot trial to determine the efficacy and safety of angina-directed medical therapy, angina plus ambulatory electrocardiographic-directed medical therapy and revascularization. The treatment of asymptomatic cardiac ischemia is double-blind and placebo-controlled. The primary end point is elimination of ischemia on the 48-hour electrocardiogram at 12 weeks. Patients will be followed-up for at least 1 year. Secondary analyses will include comparisons of the 2 medical regimens, amounts of medicine taken, and exercise versus electrocardiographic results. Eleven clinical units are recruiting 600 patients with coronary anatomy suitable for revascularization, a positive exercise stress test, and 1 or more asymptomatic ischemic episodes on the 48-hours electrocardiogram. Patients are stratified by center, symptom status and previous coronary surgery. If warranted by the pilot study results, a full-scale trial will be considered to determine whether amelioration of asymptomatic ischemia improves survival and reduces cardiovascular morbidity.


Effect of high-current stimulation in patients with sustained ventricular tachycardia rendered noninducible by antiarrhythmic drugs.

Successful antiarrhythmic drug therapy for sustained ventricular tachycardia (VT) is presumed to be related to effects on myocardium within the re-entrant circuit. To test the hypothesis that prevention of VT induction may be related to effects on myocardium other than that directly involved in the tachycardia circuit, high-current stimulation was used to achieve shorter coupling intervals in 22 patients with sustained uniform VT that was rendered noninducible by antiarrhythmic agents during stimulation at twice threshold. Sustained uniform VT was induced in 10 patients in response to high-current stimulation (group 1), including 4 tachycardias with the same morphology observed in the baseline study. There were no inducible arrhythmias in 12 patients (group 2). Patients were receiving several different antiarrhythmic regimens, but there was no particular drug associated with the induction of VT using high-current stimulation. There was no statistically significant difference between groups 1 and 2 in baseline VT cycle length (247 +/- 41 vs 253 +/- 44 ms), drug-induced increase in effective refractory period (20 +/- 15 vs 16 +/- 7%), QRS duration (25 +/- 10 vs 20 +/- 17%) or maximal current strength delivered (10.9 +/- 5.3 vs 9.3 +/- 4.0 mA). There was no significant difference in local activation with high-current stimulation between groups 1 and 2. In conclusion, sustained uniform VT was induced in 45% (10 of 22) of patients whose arrhythmias were rendered noninducible by antiarrhythmic agents during programmed stimulation at twice threshold.(ABSTRACT TRUNCATED AT 250 WORDS)


Reproducibility of programmed electrical stimulation responses in patients with ventricular tachycardia or fibrillation associated with coronary artery disease.

Invasive electrophysiologic studies were performed in 102 patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) using an aggressive programmed electrical stimulation (PES) protocol. The study was repeated after 2.0 +/- 2.9 days in all patients with no intercurrent changes in antiarrhythmic therapy. Patients with coronary artery disease (n = 72) were identified and PES results of these patients were analyzed and compared with results of patients without coronary artery disease. Multiple clinical and electrophysiologic factors were analyzed to determine any association with concordance of PES responses. No significant difference in concordance of PES responses was found in the 2 groups of patients. PES responses were groups into 3 categories: (1) noninducible, (2) nonsustained VT, and (3) sustained VT. Kappa values of PES responses of noninducible and sustained VT in both groups were higher and therefore the PES responses were more reproducible than nonsustained VT. The induction of sustained monomorphic VT was more reproducible than a PES response of nonsustained or sustained polymorphic VT. Inducible sustained VT with a rate of greater than or equal to 250 beats/min was less reproducible than induction of sustained VT with a rate less than 250 beats/min. Induction of VT by 3 extrastimuli was less reproducible than with any other mode. This short-term variability may account for false negatives associated with PES-directed antiarrhythmic therapy. Because of these findings, it is recommended that nonsustained VT and sustained polymorphic or rapid polymorphic VT should not be used as PES end points to guide antiarrhythmic therapy.


Late ventricular arrhythmia and sudden death following direct-current catheter ablation of the atrioventricular junction.

Early reports of direct-current catheter ablation (DCCA) of the atrioventricular (AV) junction for resistant AV tachycardias documented efficacy of DCCA with little morbidity. Nine patients underwent DCCA at our institution 4 to 9 years ago: 3 patients had DCCA in the coronary sinus for permanent junctional reciprocating tachycardia, 2 patients had His ablation, 2 had coronary sinus and His ablation for permanent junctional reciprocating tachycardia, and 2 had DCCA for congenital tachycardia, and 2 had DCCA for congenital junctional ectopic tachycardia. Shocks (total 1 to 5) ranged from 12.5 to 400 J. Five patients had pacemaker implant at the time of DCCA. During follow-up, 3 patients developed clinical ventricular tachycardia: all 3 had DCCA of the His bundle. One asymptomatic patient with ventricular tachycardia, who had DCCA of the bundle of His, died suddenly 6 years later with ventricular fibrillation. Autopsy revealed 2 ventricular scars: 1 extending from the AV junction and 1 in the outflow tract. No patient with DCCA limited to the coronary sinus developed ventricular tachycardia. DCCA of the His bundle can result in late ventricular arrhythmias, possibly a result of extension of the DCCA lesion into the ventricle. These late findings should be considered in evaluating the safety and efficacy and follow-up for patients undergoing radiofrequency ablation.


Reappraisal by transesophageal echocardiography of the significance of left atrial thrombi in the prediction of systemic arterial embolization in rheumatic mitral valve disease.

Systemic arterial embolization imparts a significant risk of serious complications throughout the lives of patients with rheumatic heart disease. Left atrial (LA) thrombi have been thought to be the major source of emboli. A transesophageal echocardiography (TEE) study of 260 consecutive patients with rheumatic mitral valve disease was performed during a period of 24 months, with particular reference to understanding the association between LA thrombi and embolic complications. Of these patients, 155 had predominant mitral stenosis, 24 had significant mitral regurgitation, and the remaining 81 with xenograft mitral valve replacement developed valvular dysfunction (25 resulted in predominant mitral stenosis and 56 in significant mitral regurgitation). LA thrombi were detected in 38 patients (group A) and absent in 222 (group B). Group A patients had a higher frequency of recent (less than or equal to 1 week before TEE study) and remote (greater than 1 week before) embolization than did group B patients (recent: 26.3 vs 5.4% [p less than 0.001]; remote: 18.4 vs 5.0% [p less than 0.01]). The frequency of atrial fibrillation was also greater in group A patients (100 vs 74.3%; p less than 0.001). The exclusion of patients with significant mitral regurgitation and sinus rhythm had no effect on the association between LA thrombi and evidence of previous embolization. It is concluded that TEE is a convenient diagnostic modality that can be used to identify a subset of patients with rheumatic mitral valve disease at high risk for systemic embolization. Consequently, preventive anticoagulation for possible embolic complications should be more vigorously adhered to in patients with rheumatic mitral valve disease and LA thrombi.


Usefulness of left atrial and left ventricular chamber sizes as predictors of the severity of mitral regurgitation.

Left ventricular (LV) and left atrial (LA) chamber sizes are frequently used to assist in assessing the severity of mitral regurgitation (MR). To study the reliability of these measurements in the clinical setting 2-dimensional echocardiographic measurements of the left ventricle and left atrium were obtained in 92 consecutive patients with MR present on both angiography and Doppler echocardiographic examinations performed within 2.8 +/- 2.5 days of each other. The accuracy of chamber dimensions in identifying severe MR (angiographic grade 3 to 4+) was determined in the total population and the following patient subgroups: (1) isolated chronic MR with preserved LV function inclusive of all rhythms; (2) isolated chronic MR, preserved LV function and sinus rhythm; (3) isolated chronic MR with LV dysfunction; (4) chronic MR associated with other valvular disease; and (5) acute MR. Only in subgroup 2 were chamber sizes reliable in identifying severe MR. Atrial dimensions provided the most accurate assessment with an LA volume greater than 58 ml, anteroposterior dimension greater than 45 mm and superoinferior dimension greater than 55 mm, with sensitivities of 75, 75 and 88%, specificities of 83, 100 and 83%, positive predictive values of 92, 100, and 93% and negative predictive values of 56, 60, and 71%, respectively. LV dimensions had excellent positive predictive values but lower sensitivities. Normalizing for body surface area did not improve the accuracy of uncorrected dimensions. Although increased LA and LV dimensions can identify severe MR, smaller dimensions do not exclude this diagnosis. With acute MR, atrial fibrillation, LV dysfunction or associated valvular disease, these dimensions are not reliable.


Pulmonary venous flow dynamics before and after balloon mitral valvuloplasty as determined by transesophageal Doppler echocardiography.

The pattern of left atrial filling was studied in 14 patients with severe mitral stenosis in sinus rhythm before and immediately after successful balloon mitral valvuloplasty by transesophageal pulsed Doppler echocardiography of the left superior pulmonary vein. Mean mitral valve orifice area increased from 0.8 +/- 0.1 to 2.2 +/- 0.3 cm2 (p less than 0.0001), and left atrial mean pressure decreased from 30 +/- 5 to 12 +/- 4 mm Hg (p less than 0.0001) after the procedure. After balloon mitral valvuloplasty, significant increases in peak systolic pulmonary velocity (35 +/- 16 to 44 +/- 10 cm/s; p less than 0.01), systolic flow velocity time integral (3.3 +/- 1.5 to 5.9 +/- 2.0 cm; p less than 0.001) and the ratio of systolic/diastolic pulmonary venous flow velocity time integrals (0.8 +/- 0.4 to 1.4 +/- 0.5; p less than 0.001) were observed. An acute increase in mitral valve orifice area caused no significant changes in peak diastolic forward flow velocity (40 +/- 7 to 41 +/- 9 cm/s; p = not significant [NS]), diastolic forward flow velocity time integral (4.3 +/- 1.7 to 4.6 +/- 1.8 cm; p = NS) and atrial flow reversal velocity (30 +/- 3 to 35 +/- 3 cm/s; p = NS) compared with at baseline. The results suggest that in patients with severe mitral stenosis and sinus rhythm, left atrial filling is biphasic with a diastolic preponderance, and successful mitral valvuloplasty is associated with an immediate increase in pulmonary venous systolic forward flow.


Relation between extent of cardiac muscle cell disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy.

The presence of numerous, abnormally arranged, cardiac muscle cells distributed widely throughout the hypertrophied left ventricular (LV) wall has been considered a characteristic, morphologic feature of patients dying of hypertrophic cardiomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such regions of myocardial cell disarray and the magnitude of wall thickness in the same areas of the left ventricle has not been defined. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myocardium disorganized were systematically compared in the same tissue section. No correlation was identified between wall thickness and the amount of myocardium disorganized in the same tissue sections, either when calculated separately for the ventricular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. Therefore, in patients with HC: (1) disorganized myocardial architecture is not confined to greatly thickened portions of the LV wall, but regions of the left ventricle with normal or only mildly increased thickness may also be disordered; and (2) whereas both LV wall thickening and cellular disorganization are manifestations of the primary cardiomyopathic process, these 2 morphologic features do not appear to be directly related with regard to their extent and distribution within the LV wall. These observations will potentially enhance understanding of the relation between LV structure and compliance in HC.


Effect of an anterior wall motion abnormality on the results of single-plane and biplane left ventriculography.

Although the biplane area-length method would be optimal for all left ventriculograms, 2 contrast injections are needed in laboratories with single-plane imaging equipment. The purpose of this study was to develop practical guidelines to identify the need for biplane left ventriculography in laboratories with single-plane equipment. From a retrospective analysis of 91 consecutive biplane ventriculograms (group 1), guidelines were identified that predicted when the ejection fraction calculated by the biplane method would differ significantly from the single-plane value. These guidelines were derived from information immediately available to the operator in the laboratory at the time of the procedure. Patients in group 1 were divided into 3 subgroups: biplane exceeding single-plane ejection fraction by greater than or equal to 0.05 (n = 20); single-plane exceeding biplane ejection fraction by greater than or equal to 0.05 (n = 14); and ejection fractions within +/- 0.04 by the 2 methods (n = 57). By multivariate analysis, the only predictor of a higher ejection fraction calculated by the biplane method was an anterior wall motion abnormality. This finding was tested prospectively in a separate group of 60 patients (group 2). Left ventriculograms in group 2 patients were stratified before analysis by the presence or absence of an anterior wall motion abnormality. In patients with anterior wall motion abnormalities, the biplane ejection fraction was greater than the single-plane value by 0.05 +/- 0.04 (range -0.03 to +0.15). In contrast, this difference in patients without anterior wall motion abnormalities was -0.01 +/- 0.04 (range -0.09 to +0.06; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study)

Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QTc = QT/square root of RR) proposed in 1920 by Bazett. The QTc formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QTc and linear corrected QT (QTLC). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated.(ABSTRACT TRUNCATED AT 250 WORDS)


Reversal of human platelet aggregation by low concentrations of nitroglycerin in vitro in normal subjects.

The potential reversal of platelet aggregation in vitro by nitroglycerin in low concentrations was explored using both optical aggregometry and electron microscopy. Venous blood was collected from a cohort of normal volunteers (20 men and 10 women) aged 21 to 65 years. Aggregation in platelet-rich plasma was induced by adenosine diphosphate in concentrations just sufficient to maintain a steady state of aggregation, without a spontaneous disaggregation phase (3.5 to 5 microM). Administration of nitroglycerin after the induction of aggregation caused both inhibition of the primary wave of developing aggregation and marked disaggregation. This combined effect was maximal when nitroglycerin was added at 0.5 minute after the beginning of aggregation. The observed reversal of platelet aggregation by nitroglycerin was concentration-dependent. Significant effects occurred with nitroglycerin concentrations greater than or equal to 10(-8) M. Concentration associated with 50% reversal of aggregation was 1.52 +/- 0.24 (SEM) x 10(-6) M. Electron microscopy revealed that 10(-6) M nitroglycerin induced a significant reduction in both platelet clumping and morphologic changes associated with aggregation. The results of the current study suggest a beneficial antiplatelet effect of nitroglycerin in restoring homeostasis in the face of incipient platelet aggregation. The clinical use of nitroglycerin in patients with acute ischemic syndromes may rest on this action.


Effect of acupuncture at right Hoku point on the bilateral vibration-induced finger flexion reflex in man.

Vibration applied to the volar side of the finger tip has been reported to induce finger flexion reflex. Acupuncture is reported to inhibit this vibration-induced finger flexion reflex (VFR) in the ipsilateral hand. The purpose of this study was to investigate the effect of unilateral acupuncture in the hand on VFR in both hands. As no systematic study on the relationship between VFR and the force of voluntary contraction with no vibration (Initial Force: IF) has been reported, this relationship was studied prior to the present study on acupuncture. VFR was induced by mechanical vibration on the volar side of the middle finger tip with 10 g to 500 g IF. With approximately 300 g IF, VFR was consistent. Therefore, approximately 300 g IF was applied for VFR induction to study the effect of acupuncture on VFR. A stainless steel needle was inserted into the right Hoku point and remained inserted (in-situ technique) for 10 minutes. VFR in both hands was significantly decreased by acupuncture at the right Hoku point (% control force of VFR: right, 67.8%; left, 74.6%). The present results suggest that acupuncture in the unilateral hand influences the bilateral reflex arc of VFR.


The pharmacological and pathological studies on Taiwan folk medicine (VII): The anti-inflammatory effect of Echinops grjiisii.

The hepatotoxic-protective effects of "San-fang-feng" (the root of E. grijisii) and "Lou-lu" (the root of E. latifolius) on CCl4 induced hepatotoxicity have been proposed in our previous paper (Lin et al, 1990). The anti-inflammatory effects of these two crude drugs were investigated in this experiment. The results indicated that both of them displayed pronounced anti-inflammatory activities against carrageenan-induced edema. Furthermore, in order to isolated the main active components of E. grijisii, fractions obtained from the methanolic extract of E. grijisii were investigated in mice for their 24-h LD50 and 95% confidence limits, which could be used as a guiding for further animal experiments. Our findings demonstrated that n-hexane (100,300 mg/kg), chloroform (30,100, 300 mg/kg) and ethyl acetate (30,100, 300 mg/kg) fractions could markedly inhibit the carrageenan-induced inflammation, and the main active principle was found to be concentrated in the chloroform fraction, which possessed significant inhibitory activities even more than does indomethacin.


The pharmacological and pathological studies on Taiwan folk medicine (VIII): The anti-inflammatory and liver protective effects of "mu-mien".

The bark, xylem of stem, and root of (1) Bombax malabarica DC. and (2) Ceiba pentandra GAERTN. are marked as "Mu-mien" in Taiwan. In order to clarify the pharmacological effects of these three parts, anti-inflammatory and liver protective effect were evaluated with carrageenan-induced paw edema and CCl4-induced hepatotoxicity in rats. The statistical analysis (ANOVA) shows that all of the treatment used exhibited significant anti-inflammatory activity against carrageenan-induced edema. Furthermore, the administration of root and xylem of stem of B. malabarica showed the activity even better than indomethacin group did. However, only three used parts of B. malabarica significantly alleviated liver injury induced by CCl4. Meanwhile, the histological changes in rat hepatic tissues such as fatty change, ballooning degeneration, cell necrosis, lymphocytes and Kupffer cells were also observed.


Cardiovascular effect of a senso (toad venom) - containing drug in anesthetized dogs (2): Influence of propranolol.

Effects of a Senso (toad venom)-containing drug KY on systemic hemodynamics were examined, and participation of beta-adrenoceptor in its action was evaluated by using propranolol in anesthetized dogs. KY produced a positive inotropic action, and decreased total peripheral (TPR) and coronary vascular resistances (CR), while renal vascular resistance (RR) was increased. After propranolol, KY significantly increased TPR, CR, vertebral vascular resistance and RR. KY-induced positive inotropic action was partly diminished but not abolished by beta-blockade. These results indicate that the beta-adrenergic action may be involved in the vasodilating effect of KY and partly in the positive inotropic action.


The hormonal response to HCG stimulation in patients with male infertility before and after treatment with hochuekkito.

To investigate the changes in responsiveness to hCG stimulation, and the effects on sperm qualities and basal hormone levels, 63 infertile men received 7.5qr of Hochuekkito daily for 3 months (1). Sperm density (p less than 0.01) and motility (p less than 0.01) were significantly increased after the treatment (2). Serum prolactin (p less than 0.01) and estradiol (p less than 0.01) levels were significantly decreased after the treatment (3). Enhanced responsiveness of testosterone (p less than 0.05) and estradiol (p less than 0.05) excretion to hCG injection were observed in patients with oligoasthenoteratozoospermia. These results suggested that Hochuekkito corrected Leydig cell dysfunctions in some infertile men, resulting in improvements in sperm qualities.


Inhibitory effect of ginsenosides on migration of arterial smooth muscle cells.

Migration of arterial smooth muscle cells (SMC) in the arterial wall plays an important role in the formation of intimal thickening of atherosclerotic lesions. In this study, we examined the effect of ginsenosides on SMC migration induced by platelet-derived growth factor (PDGF) and SMC-derived migration factor (SDMF). Ginsenosides had inhibitory effects on SMC migration and the striking effects were observed with ginsenoside-Rb2 and -Rc in a dose-dependent manner. These results suggest that the administration of ginsenosides on the patients may prevent intimal thickening, in part, by inhibiting SMC migration in the arterial wall.


Effects of tokishakuyakusan, keishibukuryogan, shakuyakukanzoto and unkeito on ovarian endothelin, renin and angiotensin II in pregnant mare's serum gonadotropin-treated immature rats.

We have previously proposed the ovarian ERAANPS (endothelin-rein- angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-1 (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.


Alterations of pulse by Chinese herb medicine.

Rats were injected with the crude extract of Chinese herbs, Rhizoma Coptidis, Radix Bupleuri and Cinnamomum cassia Blume. The pulse of the tail artery were examined. The results indicated that each drug had a specific effect on the Fourier components of the pulse.


Comments on nomenclature in traditional Chinese medicine.

The present article suggests that the nomenclature used in traditional Chinese medicine is currently unclear resulting in improper usage of terms and subsequent confusion. This paper is an attempt to clarify this nomenclature confusion. Traditional medicine of China should be called "traditional Chinese medicine" (T.C.M.) rather than the frequently used "Chinese medicine". The latter term fails to express the "tradition" associated with T.C.M., and also it does not distinguish between T.C.M. and modern Chinese medicine. "Oriental medicine", another frequently used term for T.C.M., has the same kind of shortcomings. The true colors of T.C.M. should be restored. The author also notes that "herb", "herbology" or "herbal medicine" is not synonymous with traditional Chinese materia medica. Herbal medicine is a type of folk medicine whereas traditional Chinese materia medica is a formal branch of traditional Chinese medicine. Furthermore, the author suggests that "acupunctology" be used when referring to the science of acupuncture whereas "acupuncture" should be used with reference to a method or perhaps the therapy of needling.


Targeted colon cancer screening: a concept whose time has almost come.

Screening of large populations for colon malignancy has been advocated in several countries to detect cancers at earlier, curable stages and/or prevent cancer by detecting and removing premalignant polyps. Ideal screening would identify subjects with the highest risk of cancer and target sensitive screening tests at this population. Recent data suggesting that environmental factors and genetic alterations contribute to increased cell proliferation in colonic mucosa provide several avenues for identification of high-risk subjects. This review examines the current literature regarding colon cancer risk factors, focusing on new ways to identify individuals who may benefit from targeted screening.


Scintigraphy in gastroesophageal reflux disease: a comparison to endoscopy, LESp, and 24-h pH score, as well as to simultaneous pH monitoring.

We compared scintigraphy to other reflux tests in 45 symptomatic patients. Sensitivity of 24-h pH score was 82%, endoscopy 64%, and LESp 33%. Scintigraphy was insensitive (36%), although 50% of patients with esophagitis had a positive test. Specificity and positive predictive value were good (all greater than or equal to 88%) in discerning patients with an abnormal 24-h pH score and esophagitis. We suggest scintigraphy as the first diagnostic test to confirm frequent reflux events (REs) and normal clearance in the subgroup of patients with severe endoscopic esophagitis, and manometry and 24-h pH monitoring when scintigraphy is negative. We also compared scintigraphy to simultaneously performed pH monitoring in detecting individual postprandial REs and their clearance. The two methods agreed in only 25% of total reflux events. Scintigraphy was superior at detection of reflux of buffered gastric contents and detection of additional REs during acid clearing intervals, whereas only the pH probe detected REs after gastric emptying. We conclude that scintigraphy has a limited role as a diagnostic test in gastroesophageal reflux disease, and much potential as a research tool, especially in combination with the pH probe.


Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility.

Ambulatory 24-h esophageal pH monitoring is increasing in popularity as the means to measure esophageal exposure to gastric juice and document the presence of gastroesophageal reflux disease, particularly before surgical therapy. Normal values for pH exposure were obtained from 50 asymptomatic healthy subjects. Receiver operating characteristic curves constructed from another 25 asymptomatic healthy subjects and 25 selected patients with other markers of increased esophageal acid exposure showed that a composite score and the percent total time pH less than 4 provide the most efficient interpretation of the test with a sensitivity of 96%, a specificity of 100% and an accuracy of 98% for the composite score, and a sensitivity, specificity, and accuracy of 96% for the percent total time pH less than 4. Repeat monitoring of healthy volunteers and symptomatic subjects in the inpatient and outpatient environment showed no significant difference, with the exception that the number of reflux episodes was significantly greater during the outpatient recording in volunteers. This did not affect the clinical accuracy of the test. Esophageal pH probes were well tolerated, but caused belching and coughing during the early part of the monitored period. We conclude that computerized ambulatory 24-h esophageal pH monitoring in the outpatient setting provides accurate and reproducible results.


Esophageal perforation: an 8-year review of a multispecialty clinic's experience.

Esophageal perforation is the most serious perforation of the gastrointestinal tract, and despite early diagnosis and treatment, mortality remains high. Twenty-four cases of esophageal perforation seen at a large multispecialty clinic between 1983 and 1991 were retrospectively reviewed. Thirteen patients presented with acute perforation, five with subacute, and six with chronic perforation. Eighteen (75%) of 24 perforations resulted from iatrogenic causes, and the rest were spontaneous. Of the iatrogenic perforations, therapeutic endoscopy and paraesophageal surgical complications were responsible for 55% and 33%, respectively. Chest pain, fever, and dyspnea were common presenting signs and symptoms of acute perforation, whereas dysphagia and supraventricular arrhythmia were more prominent features of chronic perforation. All but seven patients had surgical intervention. An overall mortality rate of 46% was noted, and despite early diagnosis and treatment, this mortality was associated with the severity of underlying disease.


Increased incidence of gallstones and prior cholecystectomy in patients with large bowel cancer.

In a retrospective study, the frequency of occurrence of gallstones and cholecystectomy in 479 patients with colorectal cancer was compared with that of 483 matched control patients with other malignancies. The mean interval between cholecystectomy and colon cancer diagnosis was 15.1 +/- 9.9 yr (range 2-53 yr), and there was no statistically significant difference, compared with the control group at 13.9 +/- 8.2 yr (range 2-31 yr). In patients with colon cancer, the general increased relative risk of concomitant diagnosed gallstones (relative risk 1.73, p = 0.0123) and the relative risk of cholecystectomy (relative risk 2.08, p = 0.0074) was statistically significant. However, when the data with regard to sex were analyzed, significant differences were observed only in women. Women affected by right colon cancer also had a statistically significant higher incidence of previous cholecystectomy (relative risk 2.86, p = 0.0096), but no significantly higher incidence of concomitant gallstones. The general increased relative risk in patients with right colon cancer and decreased risk in patients with left colon cancer of concomitant gallstones and prior cholecystectomy was statistically significant. Our data provide evidence for the hypothesis that both gallstones and cholecystectomy increase the general risk of large bowel cancer. Therefore, they are also compatible with the possibility that common risk factors causes the association between gallstones and large bowel cancer.


Prediction of Helicobacter pylori in gastric specimens by inflammatory and morphological histological evaluation.

Statistical correlations and predictive values were calculated for 330 gastrointestinal biopsies and tissues, of which 248 were from the stomach from 115 patients in this retrospective study, which graded 10 inflammatory and 14 morphological mucosal and submucosal abnormalities and compared them with the presence of Helicobacter pylori. Analysis revealed that 78 (31.5%) of the 248 stomach biopsies and tissues showed H. pylori, and 21 (8.5%) had non-Helicobacter-like bacteria, such as rods and cocci. Inflammatory components had high correlations, with specimens containing polymorphonuclear leukocytes (PMNs) showing high specificities and predictive values for a positive test, whereas the chronic inflammatory components had high sensitivities and predictive values for a negative test. Positive morphological correlations existed for mucus depletion, degeneration, regeneration, and ulceration, but intestinal metaplasia and adenocarcinoma had negative correlations. The antrum was most commonly infected, suggesting that intact healthy antral morphology and the neutral mucin in the surface epithelial cells represents the optimal environment for infection. Also, 8.5% of the gastric biopsies and tissues showed non-Helicobacter bacteria associated with inflammation, thus raising the question of colonization versus pathogenesis.


Ultrasonically guided fine-needle aspiration of liver lesions.

The aim of the present study was to determine the diagnostic accuracy of ultrasonically guided fine-needle aspiration for liver lesions detected by ultrasound scan. A total of 142 aspirations were carried out in 129 patients with unifocal or multifocal liver lesions suspected of malignancy. The aspiration was made with a 22-gauge needle, guided by ultrasound. Based on histological, cytological, and clinical findings, final diagnoses were reached in 123 patients, 96 of whom had malignant liver disease and 27 benign liver disease. Among the 96 patients with malignant liver disease, the cytological findings revealed malignancy in 78 patients (81.3%) and suspected malignancy in five patients (5.1%), but failed to demonstrate malignancy in 13 patients (13.3%). Among 27 patients with benign liver disease, all the cytological findings indicated benignancy. The overall sensitivity, specificity, and positive and negative predictive values for cytological findings were 86.5%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy of ultrasonically guided fine-needle aspiration was 89.4%. In one patient with incipient chronic disseminated intravascular coagulation, a fatal intraperitoneal bleeding complicated the procedure. We conclude that ultrasonically guided FNA for cytologic diagnosis of liver lesions is highly accurate and is only rarely associated with fatal complication.


Evaluation of duodenal papillary function by ERCP-CT and comparison with endoscopic measurement of pressure in the papillary sphincter zone.

Imaging of the main pancreatic duct on ERCP-CT (computerized tomography performed immediately after endoscopic retrograde cholangiopancreatography) was evaluated in 192 patients. Favorable images were obtained in elderly patients, as well as in those with main pancreatic duct dilation, chronic pancreatitis, papillary disease, and choledocholithiasis. In addition, we used a microtransducer inserted through a duodenoscope to measure papillary sphincter zone and main pancreatic duct pressure. We then compared the endoscopic results with the images achieved on ERCP-CT. The patients with favorable images showed higher pancreatic and papillary basal pressure and a faster wave cycle than those with poor images. In addition, significant differences in pancreatic duct pressure and basal pressure were seen. Peak papillary pressure showed no consistent correlations with imaging. Patients with favorable images exhibited an increase in the frequency of irregular papillary sphincter zone waves. We conclude from these findings that good images on ERCP-CT reflect a slow flow of pancreatic juice, which is closely associated with papillary stenosis.


Gastric emptying in childhood inflammatory bowel disease: nutritional and pathologic correlates.

To determine the incidence of gastric emptying abnormalities in children with inflammatory bowel disease, we performed dual liquid/solid-emptying studies on 25 children with ulcerative colitis (UC) and on 45 with Crohn's disease (CD) over a 6-yr period. Nutritional parameters were evaluated initially and at the time of repeat study in those with abnormal emptying after a period of nutritional rehabilitation. All UC patients and 30 of 45 with CD (67%) had normal emptying of both liquid and solid components of the meal. Fifteen children with CD had delayed emptying of the solid liquid. Fourteen of these had preceding weight loss and one had no weight gain for 3 months prior to the study. Twelve complained of upper gastrointestinal symptoms (nausea, early satiety, postprandial epigastric pain, and anorexia), and five had evidence of growth retardation. The group averaged 4.8 abnormal nutritional parameters, compared with an average of 2.2 in those with CD and normal gastric emptying. Twelve of the 15 with abnormal emptying had abnormal gastric and/or duodenal biopsies: 10 were treated with sulfasalazine and prednisone, whereas five were taking only sulfasalazine. Studies repeated 6-15 months later after establishment of weight gain by caloric supplementation showed significant improvements in gastric emptying, nutritional status, and disease activity for the group, despite persistence of upper gastrointestinal disease documented in eight patients who underwent reexamination.


Reduction of portal pressure by chronic administration of isosorbide dinitrate in patients with cirrhosis: effects on systemic and splanchnic hemodynamics and liver function.

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.


Stomal complications of gastric bypass: incidence and outcome of therapy.

Gastric bypass is an effective treatment for morbid obesity. However, it is sometimes complicated by stenosis or ulceration of the gastrojejunal anastomosis. Stomal ulceration and stenosis developed in, respectively, 12.5% and 12% of 191 patients who underwent gastric bypass. Only 3% had both complications simultaneously. The risk of developing either complication was highest in the first 2 months after surgery. Stomal stenosis responded to endoscopic dilation in all instances, and appears to be a safe and effective method of treating this problem following gastric bypass. Stomal ulceration healed with an H2 blocker and sucralfate administration in all but one patient. Postoperative weight loss was similar in patients with or without stomal stenosis or ulceration. We conclude that, although stomal complications occur in about 20% of all patients undergoing gastric bypass, they can almost always be managed by conservative therapy.


Relationship between pancreatic exocrine function and histological changes in chronic pancreatitis.

To confirm correlation between function and histology of the exocrine pancreas in chronic pancreatitis, we compared exocrine pancreatic function, as estimated by cholecystokinin secretin test (CST), with histological findings in 108 patients. Exocrine pancreatic insufficiency was graded from 0 to 4 according to the number of abnormal CST parameters. Histological findings also were graded from 0 to 4. Results of CST in 108 patients were normal (grade 0) in 52, equivocal (grade 1) in 23, and abnormal (grades 2-4) in 33. Normal histological findings (grade 0) were observed in 54 patients, equivocal (grade 1) in 15, and abnormal (grades 2-4) in 39. We confirmed that there was a significant correlation between histological grading and overall scoring (tau = 0.59, p less than 0.01) or individual parameters (tau = -0.36 for volume, -0.45 for amylase output, and -0.54 for maximal bicarbonate concentration (p less than 0.01) of CST. Sensitivity of CST was 67% in 39 patients with histologically confirmed chronic pancreatitis, specificity was 90% in 69 patients without chronic pancreatitis, based on histological evidence, and efficiency was 81%. In conclusion, we confirmed a highly significant correlation between direct function test (CST) and histology of the exocrine pancreas.


Morning versus evening dose: a comparison of three H2-receptor blockers in duodenal ulcer healing.

In a prospective, randomized, single-blind, single-center, controlled study, we compared the effectiveness of single doses of cimetidine 800 mg, ranitidine 300 mg, and famotidine-40 mg given either as evening or morning doses for duodenal ulcer healing. One hundred eighty-six male patients with endoscopically confirmed duodenal ulcer were treated for 6 wk, and ulcer healing was endoscopically evaluated. The duodenal ulcer healing rate for each of the three H2-receptor antagonists was always less after morning administration than was achieved with the respective evening regimen: 59% versus 86% for cimetidine, 83% versus 94% for ranitidine, and 93% versus 97% for famotidine, but the difference was statistically significant for cimetidine only. This study confirms the importance of nocturnal therapy for duodenal ulcer healing. The importance is obscured when H2-receptor antagonists with higher potency and long duration of action are used.


Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy.

A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.


Obstructive jaundice secondary to primary biliary involvement with Hodgkin's disease.

A 41-yr-old man presented with jaundice, night sweats, and weight loss. The patient had been on phenytoin for seizure disorder. The drug was discontinued, and a diminution of bilirubin and transaminases occurred over several weeks. Percutaneous liver biopsy revaled cholestasis at the time of maximal hyperbilirubinemia. Recurrent jaundice ensued several weeks later, and an ERCP revealed a common bile duct lesion. Laparotomy revealed Hodgkin's disease involving the common bile duct and periportal node. This cause represents the first report of extrahepatic biliary obstruction from Hodgkin's disease.


Urinary ascites in the immediate postpartum period.

New onset ascites in the immediate postpartum period is a rare occurrence most often associated with the Budd-Chiari syndrome. We report a patient who developed postpartum ascites secondary to an intraperitoneal bladder perforation.


Common bile duct stones: a cause of chronic salmonellosis.

A chronic carrier state of Salmonella spp is present in 0.15% of the population, and is believed to be related to the presence of a diseased gallbladder. We present a patient with common bile duct (CBD) stones, whose bile cultures repeatedly indicated Salmonella typhi, despite an adequate course of antibiotic treatment. The carrier state was abolished after removal of the CBD stones 4 months later. The chronic carrier state may be related to biofilm formation on the surface of the CBD stones. The removal of the biliary stones, which are the most likely reservoir for Salmonella spp, may be a crucial step in eradication of the carrier state.


Fatal pulmonary arterial hypertension complicating noncirrhotic portal fibrosis.

A 25-yr-old female with noncirrhotic portal fibrosis underwent a lienorenal shunt for variceal bleed. Ten years after shunt surgery, she presented with progressive breathlessness, and severe pulmonary arterial hypertension was detected, to which she subsequently succumbed. Autopsy revealed classical plexogenic pulmonary arteriopathy.


Octreotide in the management of postoperative enterocutaneous fistulas and stress ulcer bleeding.

We report two clinical experiences in the treatment of postoperative enterocutaneous fistula and stress ulcer bleeding with octreotide acetate (Sandostatin). In both patients, upper gastrointestinal bleeding occurred 7 days after operation, and the bleeding proved to be stress ulceration, by panendoscopic examination. Enterocutaneous fistulas also were found in both patients. One was high output (750 ml/day), and the other was low output (50 ml/day). Octreotide 50-100 micrograms was given subcutaneously every 8 h. After three doses of octreotide, a significant reduction in fistula output and control of the stress ulcer bleeding were noted. The fistulas closed promptly after nine doses of octreotide, but the first patient's fistula recurred 2 days later, with fluid losses of about 100-200 ml/day. This fistula closed spontaneously 1 month after discharge. Octreotide appears to be useful as an adjunct to the conventional treatment of enterocutaneous fistulas, especially those complicated by stress ulcer bleeding.


Gangliocytic paraganglioma of the papilla of Vater with regional lymph node metastasis.

We report a case of duodenal gangliocytic paraganglioma (GP) in a 47-yr-old man. The GP arose in the second portion of the duodenum and was shown by histological examination to consist of epithelioid cells, spindle cells, and ganglion-like cells. Although most of the reported cases of GP have been regarded as benign, in the present case we found that a lymph node in the peripancreatic region contained a metastatic tumor. This is believed to be the third documented case of GP showing regional lymph node metastasis. The metastatic tumor consisted of only epithelioid cells, without spindle cells or ganglion-like cells, supporting the hypothesis that only epithelioid cells have malignant potential.


Sepsis-associated renal vasoconstriction: potential targets for future therapy.

Systemic sepsis is associated with acute deterioration in renal function despite normal or increased cardiac output. The kidney is often structurally normal, but severe renal vasoconstriction underlies a marked decrease in the glomerular filtration rate (GFR). The mechanisms underlying renal vasoconstriction in sepsis include locally and systemically released vasoconstrictors. Novel peptide and lipid-derived mediators that have been implicated in experimental models of sepsis include endothelin (ET)-1, thromboxane A2 (TXA2), leukotrienes (LTs), and, most recently, noncyclooxygenase-derived prostaglandin F2 (PGF2) analogues. Plasma ET-1 levels are elevated in septic patients and following endotoxin administration in experimental animals; antagonism of the endogenous actions of ET-1 is associated with improvement in renal perfusion and function during experimental endotoxemia. Antagonists of the TXA2 receptor and/or TXA2 synthesis in vivo have been associated with selective improvement in renal vascular tone and preservation of GFR during experimental endotoxemia in several mammalian species. Furthermore, antagonism of the TXA2 receptor inhibits the actions of endogenously released free radical-generated PGF compounds. The latter are the most potent renal vasoconstrictors among the family of arachidonic acid derivatives. Sulfidopeptide LTs, in particular LTC4 and LTD4, are also implicated in the renal vasoconstriction that attends sepsis in rats and other experimental animals. LT hepatobiliary elimination is suppressed during sepsis and endogenous LT production is enhanced. Antagonism of LTD4 receptors is associated with amelioration of renal vasoconstriction. Taken together, these novel potential mediators of renal vasoconstriction during sepsis constitute specific molecular targets for future therapeutic interventions.


Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock.

Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.


Endotoxemia, renal hypoperfusion, and fever: interactive risk factors for aminoglycoside and sepsis-associated acute renal failure.

Sepsis and aminoglycoside administration remain leading causes of clinical acute renal failure (ARF). In recent years, a number of experimental studies from different laboratories have indicated that specific components of the septic state, most notably fever, endotoxemia, and renal hypoperfusion, can interact to induce synergistic renal damage, acting in concert to produce acute tubular necrosis and ARF. If sepsis-associated ARF has a multifactorial basis, then a number of interventions directed at one or more of its etiologic components could confer protection. In this brief review, evidence to support these pathophysiological and therapeutic considerations are presented.


Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria.

Angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria in diabetic and nondiabetic nephropathy. However, no studies have determined whether this antiproteinuric effect modifies the progression of renal insufficiency. We studied the evolution of 46 nondiabetic patients with nephrotic proteinuria treated with captopril for a minimum of 12 months. The follow-up period before captopril treatment was 12 to 18 months. At the end of follow-up, after captopril introduction (24.4 +/- 7.6 months), proteinuria had decreased from 6.3 +/- 2.5 to 3.9 +/- 3.1 g/24 h (P less than 0.001), with a mean decrease of 45% +/- 28%. The proteinuria decrease was higher in patients with reflux nephropathy, proteinuria associated with reduction of renal mass, inactive crescentic glomerulonephritis, nephroangiosclerosis, and IgA nephropathy, whereas patients with membranous glomerulonephritis and idiopathic focal glomerulosclerosis showed a poorer response. Patients were separated according to a proteinuria reduction greater (group A, 23 patients) or lower (group B, 23 patients) than 45% of the initial value. At the end of follow-up, renal function had not significantly changed in group A with respect to values at the start of treatment: serum creatinine (SCr) was 229 +/- 167 mumol/L (2.6 +/- 1.9 mg/dL) versus 203 +/- 97 mumol/L (2.3 +/- 1.1 mg/dL), and creatinine clearance (CrCl) was 0.80 +/- 0.52 mL/s (48 +/- 31 mL/min) versus 0.87 +/- 0.47 mL/s (52 +/- 28 mL/min). The slope of the reciprocal of Scr (1/SCr) showed a significantly beneficial change after captopril introduction.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of iron status by erythrocyte ferritin in uremic patients with or without recombinant human erythropoietin therapy.

Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS)


The occurrence of IgA-nephropathy in patients with diabetes mellitus may not be coincidental: a report of five cases.

We describe five patients with IgA-nephropathy complicating diabetes mellitus. In four cases, diabetic glomerulosclerosis was present at the same time. One patient suffered from dermatitis herpetiformis. The observation of the present five cases together with the notion of an increased prevalence in diabetes mellitus of celiac disease and dermatitis herpetiformis suggests that the occurrence of IgA-nephropathy in diabetic patients is not mere coincidence.


A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group.

Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation.


Extreme gestational starvation ketoacidosis: case report and review of pathophysiology.

A case of severe starvation ketoacidosis developing during pregnancy is presented. The insulinopenic/insulin-resistant state found during fasting in late gestation predisposes to ketosis. Superimposition of stress hormones, which further augment lipolysis, exacerbates the degree of ketoacidosis. In our patient, gestational diabetes, twin pregnancies, preterm labor, and occult infection were factors that contributed to severe starvation ketoacidosis. Diagnosis was delayed because starvation ketosis is not generally considered to be a cause of severe acidosis, and because the anion gap was not elevated. Improved understanding of the complex fuel metabolism during pregnancy should aid in prevention, early recognition, and appropriate therapy of this condition.


Acute renal failure following binge drinking and nonsteroidal antiinflammatory drugs.

Two college students who developed reversible acute deterioration in renal function following binge drinking of beer and the use of nonsteroidal antiinflammatory drugs (NSAIDs) are reported. Both patients presented with back and flank pain with muscle tenderness, but showed no evidence of overt rhabdomyolysis. The first case had marked renal failure, with a peak serum creatinine reaching 575 mumol/L (6.5 mg/dL), and acute tubular necrosis was documented by renal biopsy. The second case had only modest elevation in serum creatinine, and renal function rapidly improved on rehydration. The contribution of the potential muscle damage associated with alcohol ingestion to the changes in renal function in these two cases is not clear. However, the major mechanism for the acute renal failure was thought to be related to inhibition of renal prostaglandin synthesis in the face of compromised renal hemodynamics secondary to alcohol-induced volume depletion.


Acute unilateral renal failure and contralateral ureteral obstruction.

After obstetrical surgery, a young woman developed an acute renal failure of one kidney, the other having been protected by a fortuitous ureteral ligation. The possible effects of a temporary kidney exclusion on itself and on the other kidney are discussed.


Bilateral xanthogranulomatous pyelonephritis involving native kidneys in a renal transplant recipient: association with renal cell carcinoma and amyloidosis.

An unusual case of a 44-year-old male renal transplant recipient who developed bilateral xanthogranulomatous pyelonephritis (XPN) of his native kidneys is presented. Bilateral nephrectomy specimens showed classic features of XPN. In addition, there was amyloidosis involving both kidneys and a small renal cell carcinoma in the left kidney. To the best of our knowledge, such a combination of pathologic conditions in one patient has not been previously reported.


Occupational exposures and cancer of the colon and rectum.

The associations between occupational risks and colorectal cancer were examined in a Swedish population-based, case-referent study. The study was performed in Stockholm in 1986-1988 and included 569 cases and 512 referents. Relative risks (RRs) with 95% confidence intervals were calculated for different occupations/chemicals. Elevated risks of colon cancer were found among male petrol station/automobile repair workers (RR = 2.3, 0.8-6.6) and among males exposed to asbestos (RR = 1.8, 0.9-3.6), while elevated risks of rectal cancer were found among males exposed to soot (RR = 2.2, 1.1-4.3), asbestos (RR = 2.2, 1.0-4.7), cutting fluids/oils (RR = 2.1, 1.1-4.0), and combustion gases from coal/coke/wood (RR = 1.9, 1.0-3.7). However, due to a high correlation between the above-mentioned variables and the few exposed subjects, it is difficult to separate their effects properly. These analyses were adjusted for age. Further adjustments for diet, body mass, and physical activity had little or no influence on the results.


Malignant lymphoproliferative diseases in occupations with potential exposure to phenoxyacetic acids or dioxins: a register-based study.

The Swedish Cancer Environment Register (CER) is a linkage of census data (e.g., on occupations) with the Swedish Cancer Register. It has been used in different studies to generate hypotheses on occupational risk factors for malignant tumors. In this study the risk for malignant lymphoma and multiple myeloma in occupations with potential exposure to phenoxyacetic acids or other related substances were investigated. An increased standardized incidence ratio (SIR) of 1.3 for multiple myeloma was verified in farmers (no. of cases = 335). This finding applied to both sexes, and the SIR increased over successive time periods. Regarding malignant lymphoma an increased SIR of 1.2 was found in farmers (no. = 227) for the latest time period studied (i.e. 1979-1984). When non-Hodgkin's lymphoma was studied separately, an increased risk (SIR = 1.2) was found only in carpenters (no. = 149), whereas for Hodgkin's disease, sawmill workers (no. = 10) had an increased SIR of 2.1. Physicians also had an elevated risk for malignant lymphoma. A major shortcoming in register studies such as CER is that no individual exposure data on different agents are available. Lack of an association between an occupation and a specific malignant disease, therefore, may not be taken as evidence that persons within that occupation are not at increased risk for that disease.


Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.


Neurobehavioral effects of long-term occupational exposure to organic solvents: two comparable studies.

Two comparable cross-sectional studies were carried out employing the same methodology but involving two separate solvent-exposed populations (N = 90, N = 144). In each study, solvent-exposed workers were compared with age-matched controls on tests selected from the Neurobehavioral Evaluation System and on standardized questionnaire measures of symptomatology and psychiatric state. A similar pattern of results was obtained in the two studies indicating a significant effect on cognitive functioning, after controlling for confounding variables, occurring in those with more than 30 years of exposure. A more specific effect on learning processes was observed in those with more than 10 years of exposure. There were no indications in either study of a solvent-related increase in psychiatric symptoms.


Evaluation of the utility of a standard history questionnaire in assessing the neurological effects of solvents.

Using a standard battery of medical surveillance questions, a study was undertaken to determine if an increase in reported neurologic symptoms was resulting from solvent exposure at a pharmaceutical research, development, and manufacturing site. The prevalence of positive responses to 13 interval history questions pertaining to neurological symptoms was compared between those enrolled in exposed surveillance programs (n = 840) and those enrolled in other, non-solvent exposed surveillance programs (n = 1,042). The ratio of positive responders between the exposed and unexposed groups was used to generate a relative prevalence ratio (RPR). No significantly elevated RPRs were seen when the analysis was adjusted for the confounding factors of age, sex, smoking, alcohol use, noise exposure, and number of interval histories. These results suggest that workplace solvent exposures in the employees studied did not appear to result in obvious neurologic symptoms. However, low-level neurotoxic exposures can cause asymptomatic or sub-clinical disorders. Therefore, more sensitive neurotoxic surveillance systems need to be developed.


Morbidity in retired coke oven plant workers.

The effect of past occupational exposure on morbidity was studied in 354 coke oven workers in Lorraine Collieries (France) who retired between 1963 and 1982, and were still alive in 1988; 96% of them participated in this study. Occupational exposure to respiratory hazards during the working life was retraced for each subject. No significant association between the occupational exposure and the frequency of ischemic cardiopathies, arterial hypertension, gastro-duodenal ulcers, and respiratory symptoms was revealed. However, subjects who had worked on the Ovens, in the Workshops, and in the Byproducts showed a prevalence of arterial hypertension significantly higher than the non- or slightly exposed subjects. The healthy worker effect phenomenon, the exclusion of deceased subjects, and the small size of this retiree population may conceal possible differences between exposure groups.


Morbidity among municipal waste incinerator workers.

Incinerator workers are exposed to many toxic compounds, most notably heavy metals. We evaluated medical and exposure monitoring data of an actively employed cohort of Philadelphia incinerator workers following an Agency for Toxic Substances and Disease Registry site survey and National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation (HHE). Of the many airborne samples taken by NIOSH, only four of the personal breathing zone samples were above OSHA or ACGIH standards: one for lead, one for phosphorous, and two for total particulates. Because samples were taken during limited operations (only one of the two incinerators were operating), the results may underestimate historical exposures at this site. We limited our medical analysis to the 86 male workers who participated in the HHE out of the 105 active employees. The 86 employees were divided into potential high and low exposure groups based on a work site analysis done by an independent industrial hygienist. Eight individuals had at least one elevated biological index indicating exposure to a heavy metal. These elevations, however, were unrelated to the workers' exposure categories. Furthermore, no clinically significant mean blood or serum measurements were noted. Thirty-four percent of the workers had evidence of hypertension which increased the risk of significant proteinuria. Neither hypertension nor proteinuria were related to exposure group. Changes in pulmonary function related only to smoking status. Although there was some evidence of an increased risk of exposure to products of incinerator waste, we could not relate the few elevated biological tests to exposure classification. Additional studies are needed to assess the potential health effects of municipal waste incinerator by-products.


Responses among New Jersey's largest employers to legislation restricting smoking at the worksite.

In 1985, New Jersey enacted a state law requiring that employers with more than 50 employees implement policies to control smoking in places of employment. The 104 largest private employers in New Jersey were surveyed in 1988 to assess their worksite smoking policies. Of the 92 respondents, 97% had implemented restrictive workplace smoking policies. Only 12% of respondents had implemented such policies prior to the date required by the law, and 86% cited the law as the reason for restricting smoking in the workplace. Over two-thirds of respondents placed restrictions on smoking in open areas, while only one-third restricted smoking in private offices. Nonsmoking employees were reported by 80% of respondents to be supportive of restrictive smoking policies, but 23% reported dissatisfaction by their smoking employees. The New Jersey law appears to have been an important factor in the adoption of work place smoking restrictions by the state's largest employers.


Microgranulomatous aspergillosis after shoveling wood chips: report of a fatal outcome in a patient with chronic granulomatous disease.

Chronic granulomatous disease is characterized by recurrent infections that result from an inability of phagocytes to kill organisms effectively. We describe a patient with this disease who developed aspergillus pneumonia after shoveling moldy cedar wood chips. Despite aggressive therapy, the patient's condition deteriorated and he died. At autopsy, the lungs revealed diffuse granulomas, all of the same age, with aspergillus organisms confined to the granulomas. We propose the term "microgranulomatous aspergillosis" for this response, which does not conform to the commonly described aspergillus syndromes. We conclude that susceptible immunosuppressed patients should be advised to avoid occupational situations where high spore concentrations are generated.


Victoria M. Trasko: champion of state-based surveillance of occupational diseases in the United States, 1937 to 1971.

Victoria M. Trasko (1907-1979), a relatively unknown figure to many currently practicing occupational health specialists, was a pioneer in state-based surveillance of occupational diseases in the United States. To highlight her accomplishments during her career with the United States Public Health Service from 1937 to 1971, this report briefly reviews her publications on occupational disease surveillance. Her span of work includes guidelines for state industrial hygiene programs, numbers of workers in state occupational health programs, compilation of state and local laws related to industrial hygiene, proposals for standardized reporting of occupational disease, and analysis of trends in workers' compensation and mortality statistics for occupational diseases. She pilot tested the first state-based model system for occupational disease reporting in the United States. She documented the great difficulty experienced by states in getting physicians to report cases of occupational diseases, and pointed out that surveillance of other existing data sources was worthwhile, at least for some occupational diseases. She was the first to report on the distribution of silicosis cases in the United States by state, industry, and job title. She was the first to comment on mortality trends for the pneumoconioses and to document problems in comparability between different International Classification of Disease (ICD) periods.


Hypertensive nephropathy: is a more physiologic approach to blood pressure control an important concern for the preservation of renal function?

During the past 2 decades, there have been important reductions in stroke-related morbidity and mortality due to better control of hypertension. However, there has been a lesser effect on the reduction of coronary mortality and far less of an impact on all other forms of noncardiovascular disorders such as renal disease. This suggests that our ability to prevent hypertensive nephrosclerosis through traditional methods of lowering blood pressure may not be as effective as was once thought, particularly in high-risk patients such as blacks, diabetics, the elderly, and patients with preexisting renal disease. One reason that may partially explain the difficulty in protecting the renal circulation from hypertensive damage is the interaction between antihypertensive medications and the aged-related decline in renal perfusion. Depending on their mechanism of action, antihypertensive agents may impair renal blood flow (through plasma volume contraction or reduction) and further aggravate the age-related decline in renal perfusion. A worsening of renal perfusion may activate counterregulatory neurohormonal mechanisms, such as the renin-angiotensin-aldosterone system, which in turn may place the patient at increased risk for the development of glomerulosclerosis through promotion of vascular or mesangial hypertrophic changes or increased intraglomerular pressure, despite an associated reduction in systemic blood pressure. Since antihypertensive agents have such varied effects on systemic and renal hemodynamics, an understanding of the antihypertensive actions in a given patient may have significant influence on renal function. Thus, an improved understanding about the effects of aging and hypertension on the renal microcirculation will hopefully facilitate a more physiologically appropriate antihypertensive medication selection with the expectation that renal function will be benefitted over the long term.


Selecting optimum antihypertensive therapy: indications for choosing a calcium channel blocker.

In choosing the optimum antihypertensive agent for an individual patient, various factors should be considered. Demographic characteristics (e.g., age, gender, race) and the circadian pattern of blood pressure elevation may influence the response to therapy. Concomitant therapy for coexisting medical disorders must be evaluated for possible drug interactions. Calcium channel blockers, which can be used in any age group, may be particularly useful in hypertensive patients with certain concurrent conditions (e.g., coronary artery disease, migraine, or gastrointestinal motility disorders). Life-style, including occupation and leisure-time activities, may contraindicate the use of certain drugs in a particular patient. It also may be necessary to consider the economic status of the patient, particularly in the elderly, who often have limited disposable income. Since to a great extent successful therapeutic management of hypertension depends on patient compliance, reduced frequency of dosing (i.e., once or twice daily) is desirable. The clustering of morbid events in the hours immediately following awakening highlights the need for therapy that provides 24-hour control, thereby ensuring adequate pharmacodynamic effects during that crucial period. The challenge is to select the most appropriate first-line agent (diuretic, beta blocker, calcium channel blocker, or angiotensin-converting enzyme inhibitor) for a particular patient.


Evolution of the treatment of hypertension: what really matters in the 1990s?

Over the past decade we have seen a shift in the strategy for the treatment of hypertension, from stepped therapy--involving a highly structured, unvarying series of steps--to recommendations for more individualized treatment. How shall we accomplish that goal? Severe hypertension provides a clear indication to bypass earlier recommendations. Demographic data such as age, gender, and race, often cited, have proved less helpful. Concomitant medical problems, which are found in greater than 50% of hypertensive patients, are most often the crucial determinants in the selection of antihypertensive therapy. Concurrent coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, chronic obstructive pulmonary disease, borderline cognitive dysfunction, anxiety, and depression are all common. Each has implications for antihypertensive therapy. Moreover, blood pressure reduction is a surrogate for our real goal, which is reduction of cardiovascular risk. Thus, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, hyperlipidemia, and insulin resistance as additional risk factors in hypertension. Consideration of all of these factors makes it possible to individualize antihypertensive therapy in most patients.


Novel drug-delivery systems for hypertension.

Although novel controlled-release drug-delivery systems have been used in other areas of medicine, their application in the treatment of hypertension has been relatively recent. Biotechnical use of chemical-dispensing systems has been applied to propranolol, clonidine (the transdermal therapeutic system), nifedipine (the gastrointestinal therapeutic system), verapamil (the sodium alginate and spheroidal oral-delivery absorption system), felodipine (the hydrophilic gel principle), metoprolol succinate (the multiple-unit pellet system), and diltiazem (one system comprising sustained-release beads and the other utilizing the patented Geomatrix extended-release system). Oral drug-delivery systems allow antihypertensive agents that previously had to be administered two to four times daily to be administered once each day. Potential disadvantages of the oral controlled-release products include delayed attainment of pharmacodynamic effect, unpredictable or reduced bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosing inflexibility, and increased cost. Potential advantages include reduced dosing frequency, enhanced compliance and convenience, reduced toxicity, stable drug levels, uniform drug effect, and decreased total dose. Although skin reactions are common, the transdermal drug delivery of clonidine provides another innovative approach to supplying transcutaneous, controlled, continuous delivery of drug for 7 days. It is possible that future research will prove that the agents that provide complete 24-hour control may reduce the cardiovascular events associated with the early-morning blood pressure surge. This evolution in antihypertensive therapy to achieve once-daily dosing may prove to be of great value to both physicians and patients in the 1990s.


Clinical experience with a once-daily, extended-release formulation of diltiazem in the treatment of hypertension.

Although calcium channel blockers were only recently approved for antihypertensive therapy, 10 years of data have demonstrated their beneficial effects. Among the available calcium channel blockers, diltiazem hydrochloride appears to have a highly favorable side-effect profile. A new, extended-release formulation of diltiazem has been developed for the treatment of essential hypertension. The safety and efficacy of various once-daily doses of this new formulation were assessed in two multicenter studies. The first study was a dose-ranging trial of 275 patients with mild-to-moderate hypertension. Patients were randomly assigned to once-daily diltiazem (120, 240, 360, or 480 mg) or placebo for a 4-week, double-blind treatment period. A patient subgroup underwent ambulatory blood pressure monitoring (ABPM) twice. Once-daily diltiazem (dose range, 240-480 mg) significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion. ABPM results demonstrated consistent decreases in systolic and diastolic blood pressure throughout the 24-hour dosing interval. Dosages greater than or equal to 240 mg/day provided trough drug blood levels within the therapeutic range (i.e., greater than or equal to 40 ng/mL). The second study was a forced-escalation trail of 115 patients with mild-to-moderate hypertension. Patients were randomized to treatment with either placebo or escalating dosages of diltiazem (180 mg/day for 2 weeks, 360 mg/day for 2 weeks, and then 540 mg/day for 2 weeks). Statistically significant (p less than 0.01) reductions in supine systolic and diastolic blood pressure were observed with the 360 mg/day and 540 mg/day dosages. Dose escalations resulted in incremental blood pressure reductions and an increase in the percentage of responders. There was a significant correlation between diltiazem peak and trough plasma concentrations and antihypertensive effects in both studies, supporting the 24-hour efficacy of this extended-release formulation. Diltiazem administered once daily was found to be safe and well tolerated by the patients in these studies; adverse events were generally mild, with an incidence similar to placebo. Results indicate that this new extended-release formulation of diltiazem, administered once daily in doses greater than 120 mg, effectively lowers systolic and diastolic blood pressure in patients with mild-to-moderate essential hypertension.


Marked parental consanguinity as a cause for increased major malformations in an Israeli Arab community.

It is common among Israeli Arabs who live in the villages to prefer consanguineous marriages, particularly among first cousins. In addition, such villages are populated by a few (less than 20) original families, and inter-family/inter-village marriages are infrequent. The purpose of this study was to examine the consequences of such "consanguinity" in Taibe, a large Arab village, 30 km from Tel Aviv. Six hundred ten families were prospectively ascertained through infants who were routinely seen in the local "Well Baby Clinics." A significant increase in the incidence of major malformations was noted in relation to the closeness of the parental relationship. For the index cases group the prevalence of individuals with major malformations were 5.8% in the product of inter-village marriages, 8.3% in the intra-village non-related matings, 15.1% in the distant consanguineous group, and up to 15.8% in the progeny of first-cousin marriages (P less than 0.001). In the siblings of these index cases, the frequency of major malformations was 4.3%, 4.5%, 10.5%, and 10.3%, respectively. Analysis of the major malformations by each body system showed the same trend. The study demonstrates a marked high rate of consanguineous marriages, whose effect leads to a marked increase in major malformations and thus a prominent public health problem in such villages. This requires a unique genetic counseling approach.


Reproductive decision making of aunts and uncles of a child with cystic fibrosis: genetic risk perception and attitudes toward carrier identification and prenatal diagnosis.

This paper evaluates the perceived genetic risk, the perceived burden, the impact on reproductive decision making, and the attitudes of aunts and uncles of a child with cystic fibrosis toward carrier identification, prenatal diagnosis, and pregnancy termination. A mailed questionnaire was sent to the aunts and uncles of 32 CF children (1) who attended the Paediatric Department of the University Hospital and (2) whose parents agreed to give the names and addresses of their sibs. The results for the 109 respondents aged less than 40 years are discussed. About one-fourth of them was aware of the "approximate" level of the risk to be a carrier of the CF gene and/or of the risk of having a CF child themselves. Nevertheless the subjective evaluation of the genetic risk has played a part in the reproductive decision-making process of at least 39% of the respondents. About three-fourths would (probably) make use of heterozygote detection and would (probably) ask for prenatal diagnosis should they become pregnant. It is striking that less than half of the group would interrupt the pregnancy should the fetus be affected. The intention to use prenatal diagnosis was significantly correlated with age and educational level while the acceptance of pregnancy interruption was significantly correlated with perceived burden, respondents' age, and health situation of the proband.


Ullrich-Turner syndrome with unilateral agenesis of breast, nipple, and pectoralis major.

A 16-year-old girl with mosaic Ullrich-Turner syndrome [45,X/46,X,i(Xq)] had agenesis of the left breast, nipple, pectoralis major, and agenesis of hair follicles of the left axilla. This appears to be the first description of this anomaly in the Ullrich-Turner syndrome.


Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3.

A two month-old girl was diagnosed as a case of Rubinstein-Taybi syndrome (RTS) on typical facial dysmorphism, broad and duplicated distal phalanges of thumbs and halluces, growth retardation and psychomotor development delay. Chromosome analysis demonstrated a de novo pericentric inversion of one chromosome 16: 46,XX,inv(16)(p13.3;q13). This association confirms assignment of a locus for RTS gene to 16p13.3, as two others translocations involving the same breakpoint have already been reported.


Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome?

A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum.


7p deletion syndrome: an adult with mild manifestations.

Deletion of 7p results in a wide spectrum of congenital abnormalities and minor facial and hand anomalies, often including craniosynostosis. We report on the oldest recognized patient with this disorder, a 24-year-old woman with an interstitial deletion from p15.3-p21.2 or p21.3. The manifestations in this patient are milder than those of previously described patients, and include borderline mental retardation, short stature, minor facial anomalies, and several skeletal changes. The absence of craniosynostosis in this patient is noteworthy, given previous suggestions that there is a specific locus for this finding in the 7p region. Twelve cases of 7p deletion, in which the missing segment overlaps that of the current case, are reviewed. This case delineates a broader spectrum for patients with 7p deletion syndrome.


Unbalanced translocation 46,XY,-15,+der(22)t(15;22)(q13;q11)pat: case report and review of the literature.

We present a boy with a rare unbalanced translocation 46,XY,-15,+der(22),t(15;22)(q13;q11) pat. Previous reports of similar chromosome findings mention only the Prader-Willi phenotype. At birth, his manifestations included severe hypotonia and lethargy, (typical of deletion of 15pter----q13); hypertelorism, down-slanting small palpebral fissures, preauricular tags, long philtrum (typical of duplication of 22pter----q11); severe laryngotracheomalacia, and proximal implantation of the thumb. In a review of the literature on chromosome abnormalities involving duplication of 22q11 the associated clinical phenotype consists of mild mental retardation, microcephaly, hypotonia, hypertelorism, down-slanting palpebral fissures, a long philtrum, cleft or highly arched palate, and ear abnormalities. Preauricular pits or tags are common. Cardiovascular defects, renal and genital problems and dislocated hips are frequently present. Anal atresia and colobomata are mainly seen in cat-eye syndrome, the phenotype associated with idic 22q11. Our findings indicate that patients with unbalanced t(15;22) can have manifestations of the dup 22q11, in addition to the previously reported Prader-Willi phenotype, even if the duplicated segment is small.


Unusual short rib-polydactyly syndrome.

We present a case of lethal short rib-polydactyly syndrome (SRPS) that cannot be categorized into the existing classification. A nosologic discussion is presented. To our knowledge, situs inversus totalis, as in our case, has not been described before in any SRPS.


Complementary duplication and deletion of 17 (pcen----p11.2): a family with a supernumerary chromosome comprised of an interstitially deleted segment.

A sister and brother were investigated because both were developmentally delayed although they had somewhat different physical anomalies. The girl was found to have an interstitial deletion of chromosome 17. Her karyotype was 46,XX,del(17) (pter----p11.2::cen----qter). Her brother had normal chromosomes in peripheral lymphocytes. Cytogenetic investigation of the mother showed the presence of the same deletion as in her daughter and a small supernumerary chromosome. The supernumerary chromosome appeared to contain the material deleted from the short arm of 17 since the mother's phenotype was normal. Study of skin fibroblasts in her son showed that he was mosaic for a normal cell line and one that contained the extra small chromosome; thus, he had mosaic partial trisomy 17(cen----p11.2). The origin of the centromere and telomere(s) of the small supernumerary chromosome in this family presents an interesting problem.


Early neurological manifestations and brain anomalies in Marden-Walker syndrome.

We report on an infant with the Marden-Walker syndrome. In addition to the consistent neurological abnormalities described previously in this syndrome, the infant had a striking neurological constellation, absence of primitive reflexes, jerky eye movements, failure to habituate to repeated stimuli, inadequate behavior development, and absence of orientation responses to visual or auditory stimuli. Muscle biopsy showed a similar pattern to the congenital fiber-type disproportion. Ultrasonograms and magnetic resonance imaging of his brain demonstrated absence of corpus callosum, colpocephaly, hypoplastic brainstem, hypoplasia of the inferior vermis and of the cerebellar hemispheres. These findings further delineate this syndrome and suggest that prenatal central nervous system (CNS) dysfunction, mainly of the cerebellum and brainstem, may play a significant role in the pathogenesis of the Marden-Walker syndrome.


Familial intestinal malrotation with midgut volvulus and facial anomalies: a disorder involving a gene controlling the normal gut rotation?

We report on 2 sisters with congenital midgut volvulus. Both had similar facial changes different from those of their parents and the other 2 unaffected sibs. Both parents had normal barium meal roentgenograms. The occurrence of these abnormalities in sibs born to parents with apparently normal gastrointestinal tract anatomy suggest autosomal recessive inheritance, although a coincidence, multifactorial or autosomal dominant inheritance with nonpenetrance in either of the parents cannot be excluded.


Glaucoma-lens ectopia-microspherophakia-stiffness-shortness (GEMSS) syndrome: a dominant disease with manifestations of Weill-Marchesani syndromes.

We report on a syndrome of progressive joint stiffness, glaucoma, and lens dislocation observed in three generations and compare it with two previous records of short stature, lens ectopia, and articular limitation. This family confirms the existence of a dominant Weill-Marchesani-like syndrome. We suggest that it could be related to the Moore-Federman syndrome. We coin the acronym GEMSS syndrome (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) to distinguish this dominant Weill-Marchesani-like syndrome from the classic, recessively inherited syndrome.


Hawkinsinuria in two families.

Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5-oxoproline are also found only in infancy, while 4-hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds.