Preclinical Safety Evaluation of Dilevalol (SCH 19927), an Antihypertensive Agent, in the Rat

Dilevalol (SCH 19927) is an antihypertensive agent with directvasodilating properties due to ß₂-adrenergic receptoragonist activity and nonselective ß-receptor blockingactivity. In acute (single dose) oral and parenteral studiesa low order of toxicity was observed. Clinical signs observedat the higher doses included salivation, prostration, tremors,and convulsions. In multidose oral studies dilevalol producedan increase in mean absolute and/or relative heart weights observedas early as 1 month in the high-dose (300 mg/kg) rats and atall dose levels (35, 90, 220 mg/kg) in rats treated for 1 year.There were no microscopic changes that could be associated withthe change in heart weight. Intraalveolar macrophages were observedin the lung tissue of rats treated for 3 months or 1 year withan increase in relative lung weights noted in the high-dose(220 mg/kg) group treated for 1 year. In a 2-year rat study,no evidence of oncogenicity was observed. On the basis of thesestudies, dilevalol has a low order of toxicity and lacks oncogenicpotential in the rat.     

Successful Percutaneous Extraction of a Chronic Left Ventricular Pacing Lead

This report describes a patient with a chronic endocardial left ventricular pacing lead. To avoid the risk of future embolization, it was felt that the lead should be removed and right ventricular pacing established. The lead was carefully evaluated by transesophageal echocardiography to exclude adherent thrombus. Successful percutaneous lead extraction was accomplished without sequelae, thus avoiding the morbidity of a thoracotomy.     

The linked φψ chain plot for visual comparison of the backbone conformation of peptides and proteins

A new graphic method is described for presenting in two dimensions the φ and ψ dihedral angles that describe the backbone conformation of a peptide or protein chain. For each residue in sequence, φ and ψ are plotted as dots on the y-axis above the next two points on the x-axis representing the residue number. Each dot is linked to the next dot by a slanting line segment (link) and each cis-peptide bond (ω～0°) between residues X and Y is indicated by marking dots ψx and φy with a diamond. This linked φ and ψ chain plot is more useful than an unlinked φ and ψ chain plot for visually recognizing helices, sheets and turns and for graphically comparing several protein structures. Overlaying the linked φ and ψ chain plots for 15 β-hairpins classified as type-I' β-turns revealed that three were significantly different from the rest. The dihedral angles (mean f standard deviation) of the loop residues (L1, L2) for a cluster of 12 β-hairpins with an inverse-common, type-I′β-turn (φ_L1= 52±7°, ψ_L1=40±8°, φ_L2=80±9°, ψ_L2= -1±13°) are similar to the standard dihedral angles for the type-1′ turn (60, 30, 90 and 0°, respectively).     

Diaphragm Strength in the Shrinking Lung Syndrome of Systemic Lupus Erythematosus

SUMMARY The cause of the reduced lung volume in the ‘shrinkinglung’ syndrome of systemic lupus erythematosus (SLE) wasinvestigated in 12 patients with the condition. Nine patientsdescribed persistent episodes of pleuritic chest pain. Narrowsection (3 mm) computed tomography of the thorax revealed nointerstitial fibrosis or significant pleural disease. Assessmentof diaphragmatic function using manoeuvres more reliable thanthe maximal occluded efforts previously used alone to assessrespiratory muscle strength, showed that diaphragm strengthwas unequivocally normal in nine of 12 patients. In three, maximumtransdiaphragmatic pressure was moderately reduced, but phrenicnerve stimulation demonstrated that this was due to incompleteactivation of the diaphragm during a maximal voluntary effort,rather than to a primary abnormality of the diaphragm. Resultsof maximum lung recoil pressures and dynamic compliance, andanalysis of the 12–s maximum voluntary ventilation, suggesteda restriction in chest-wall expansion, although it was not possibleto identify the underlying cause of this on the basis of ourresults. We conclude that the ‘shrinking lung’ syndromeof SLE is not explained by a primary abnormality of the diaphragm.     

Skeletal Manifestations of Idiopathic Bone Sclerosis

Six cases of idiopathic bone sclerosis involving the distal extremities are presented. The lesion demonstrates cortical and endosteal thickening parallel to the long axis of the involv ed bone without concomittant soft tissue or other bone abnormality. Differential diagnoses are discussed. TWO cases with long-term follow-up demonstrate the radiographic stability of the condition arid its lack of activity with radionuclide bone imaging.     

High Resolution Computed Tomography in the Evaluation of Glomus Tumours of the Petrous Temporal Bone.

Recent advances in surgery have made it possible to resect virtually all glomus tumours involving the petrous temporal bone. The surgical approach depends on the extent of the tumour and the degree of involvement of the intrapetrous portion of the internal carotid artery. High resolution computed tomography offers an accurate means of staging these tumours and of distinguishing them from an aberrant internal carotid artery. The CT scans of eighteen patients thought clinically to have glomus tumours of the temporal bone were reviewed. The final diagnoses in our series included twelve glomus turnours, three aberrant internal carotid arteries, two carcinoid tumours and one meningioma.     

Antispermatozoal Antibodies in Three Men With Infertility Due to Congenital Aplasia of the Vasa Deferentia

ABSTRACT: Men presenting with azoospermia due to aplasia of the vas deferens have commonly been considered to be infertile without hope of treatment. With improved methods of artificial insemination however, and more particularly with the advent of in vitro fertilization, it has been suggested that usable spermatozoa may be able to be drawn from the epididymes of such men so that fertilization is achieved. The clinical situation of such men is analogous to that of long term vasectomised patients, 60% of whom are known to produce antibodies to spermatozoa which would interfere with the fertilization process. It was therefore decided to attempt to draw fluid from the epididymes of three such patients and at the same time conduct immunological studies on their sera, seminal fluid and, where available, epididymal fluid. Unfortunately, the spermatozoa obtained from all three men lacked sufficient progressive motility for use in in vitro fertilization. In addition, all men had antispermatozoal antibodies in their sera. Two of them also had antispermatozoal antibodies in their epididymal fluid and on their sperm, one at the same titer as in his serum. Since it is known that antibodies coating sperm reduce the changes of fertilization it is suggested that their presence should be assessed in all such men being considered for treatment. In addition, these studies demonstrate that antispermatozoal antibodies can enter the male tract at the level of the epididymis or higher and there were strong suggestions of local antibody production at this level in the tract.     

Hepatic HMGCoA reductase in human cholelithiasis: effects of chenodeoxycholic and ursodeoxycholic acids*

Abstract. To study further the role of hepatic cholesterol synthesis in patients with gallstones, the activity of the rate-limiting step in cholesterbgenesis, hydroxy-methyl glutaryl co-enzyme A reductase (HMGCoAR), was measured in operative wedge liver biopsies from ten patients with untreated cholesterol gallstones, six with pigment stones and ten controls. Hepatic HMGCoAR was also measured in six patients with cholesterol-rich gallstones treated for 1–24 months with 14-6-18-6 mg chenodeoxycholic acid (CDCA) kg^-1 day^-1, in two patients with radiolucent pigment stones treated with 17-3 and 17-7 mg CDCA kg^-1 day^-1 and in ten other patients with cholesterol-rich stones given 4–5-7-2 mg ursodeoxycholic acid kg^-1 day^-1 for 1–6 months. HMGCoAR activity was also related to the free and esterified cholesterol content of both hepatic homogenates and the microsomal fractions. Compared with the controls (HMGCoAR activity 14-6±1 6 (SEM) pmole mg microsomal protein^-1 min^-1), the mean activity in untreated cholesterol cholelithiasis was 32 2 ±2-0 (P < 0–001), but was near normal in patients with pigment stones (16-2 + 1 5). In cholesterol gallstone patients, chenodeoxycholic acid treatment reduced the mean enzyme activity by 51% compared with the untreated gallstone group (P < 0001) and in smaller doses, ursodeoxycholic acid therapy lowered it by 40% (P < 0001) but in the two patients with pigment stones, CDCA did not seem to affect HMGCoAR activity. Despite this four-fold variation in enzyme activity, there were no significant differences in mean free or esterified cholesterol concentrations in whole liver homogenates or in the microsomal fraction from any of the patient groups. Presented in part at the European Society for Clinical Investigation, Rotterdam, April 1978 (Maton P.N. & Dowling R.H (1978) Eur J Clin Invest 8, 329 (abstract)) and at the V International Bile Acid Meeting, Freiburg, June 1978 (Maton P.N. & Dowling R.H. (1978) in: Biological Effects of Bile Acids (ed. by G. Paumgartner, A. Stiehl and W. Gerok), pp. 91–98. MTP Press, Lancaster).