Preservation of All Chordae Tendineae and Papillary Muscle During Mitral Valve Replacement with a Tilting Disc Valve

Mitral valve replacement was performed in 21 patients using a surgical technique that preserves the entire papillary muscle and chordal apparatus. With this technique, the anterior mitral leaflet is split from the center of the free edge toward the annulus. Bilateral incisions are made from the proximal end of this split to the two mitral commissures, detaching the anterior leaflet from the annulus. These two halves of the leaflet, with all chordae intact (corresponding to the anterolateral and posteromedial papillary muscles), are judiciously trimmed to remove areas of leaflet untethered by chordae tendineae and (when necessary) fibrous thickening; then swung posteriorly and sutured to the posterior mitral annulus using mattress sutures with pledgets. This surgical technique is expected to favor the preservation of left ventricular function and avoid occurrence of irreversible left ventricular dilation/dysfunction, and has been used successfully for calcific and degenerative etiologies, using both tilting disc valves and porcine bioprostheses. It is especially useful in the implantation of tilting disc and bileaflet mechanical prostheses because anterior subvalvular chordae tissue may interfere with the disc excursion and relocated to the posterior leaflet annulus.     

THE EFFECT OF ALPHA ADRENERGIC MANIPULATION ON THE 24 HOUR PATTERN OF CORTISOL SECRETION IN MAN

We have studied the role of central alpha-1 adrenoceptor mechanisms which stimulate cortisol secretion throughout the 24 h period in man. Six normal subjects were given 24 h i.v. infusions of the alpha-1 adrenoceptor agonist methoxamine, the alpha-1 antagonist thymoxamine, and saline under double-blind conditions. The only cardiovascular effects of these adrenergic manipulations was a slight bradycardia accompanying the methoxamine infusion. The methoxamine infusion was accompanied by higher concentrations of cortisol than the saline infusion during waking hours and the food related secretory surges were exaggerated, while the converse held with thymoxamine. In contrast, the nocturnal surge of cortisol secretion was unaffected by these adrenergic manipulations. These findings suggest that an alpha-1 adrenoceptor mechanism contributes to the maintenance of cortisol secretion during waking hours, but not at night.     

The Effect of Etiocholanolone on Granulocyte Kinetics

The effect of etiocholanolone on granulocyte kinetics in 12 hematologicallynormal patients has been investigated using the technic of ³H-DFP labelingof autologous blood in vitro.

Baseline determinations of the total blood granulocyte pool (TBGP), thecirculating pool (CGP), and the marginated pool (MGP) were performed.The values for the total blood granulocyte pools were similar to those previously reported. Following the administration of etiocholanolone, there was a98 per cent increase in the TBGP, which was considered to be due to mobilization of granulocytes from the bone marrow reserve. There was no change inthe ratio of CGP to MGP.

These studies suggest that etiocholanolone may be a useful agent for theestimation of bone marrow reserve.

Submitted on November 21, 1966 Accepted on April 13, 1967     

OSTEOLYTIC PROPERTIES OF THE SYNOVIAL-LIKE TISSUE FROM ASEPTICALLY FAILED JOINT PROSTHESES

Relationships were found between the bone-resorbing abilityof conditioned media (CMs) from cultures of peri-prosthetictissues and their levels of bone-remodelling agents. Bone-resorbingactivity was measured by ⁴⁵Ca release from pre-labelled mousecalvaria and 23 of 40 CMs exhibited bone-resorbing activity.Cytokine and prostanoid levels in the CMs were measured by immunoassay,and the levels of interleukin (IL)-1ß, IL-6, tumournecrosis factor (TNF) and prostaglandin E₂ (PGE₂) correlatedwith each other, except for the latter two. Significantly higherlevels of IL-6 were present in those CMs with bone-resorbingactivity than in those without, and a similar pattern was observedfor PGE₂ and IL-1ß. However, some CMs with high levelsof IL-1ß, IL-6, TNF and PGE₂ failed to induce resorption,whereas a few CMs with low levels of these agents induced resorption.Moreover, neither dialysis of CMs nor addition of neutralizingantisera to IL-1 and IL-1ß to CMs, either alone orin combination, reduced the bone-resorbing activity of the CMs.It is considered that these agents may act synergistically tomediate osteolysis around failed joint implants, but that otherunidentified bone-resorbing agent(s) must be involved. KEY WORDS: Implant failure, Pseudosynovial membrane, IL-1ß, IL-6, TNF, TGFß1, Prostaglandins, Bone resorption, Leucocytes     

CRF IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING''S SYNDROME: A COMPARISON WITH THE DEXAMETHASONE SUPPRESSION TEST

Accurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin-releasing factor (CRF-41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high-dose dexamethasone suppression test (8 mg/day for 48 h). Of 20 patients with confirmed Cushing's disease (pituitary-dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high-dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF-41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high-dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high-dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.     

Factor X and its deficiency states

Summary . Factor X is one of the vitamin-K-dependent serine proteases. As a result of its position at the convergence of the intrinsic and extrinsic pathways of the clotting cascade, it plays a crucial role in blood coagulation. Factor X interacts with components of both pathways of coagulation, leading to its activation and the formation of the prothrombinase complex.
The gene for factor X has been cloned and sequenced and maps to the long arm of chromosome 13, approximately 2.8 kb downstream of the factor VII gene. Each of the exons of factor X encodes a specific functional domain within the protein. In terms of its gene structure and amino acid sequence, factor X shows significant homology with other vitamin-K-dependent clotting factors, suggesting an origin in some common ancestral protein.
Factor X deficiency is one of the rarest of the inherited coagulation disorders. Such deficiencies are inherited in an autosomal recessive manner and are characterized by a variable bleeding tendency. In its homozygous form, factor X deficiency has an estimated prevalence of 1:500 000 but in its heterozygous form it has an estimated frequency of ∼1:500 although affected individuals are often clinically asymptomatic.
Acquired deficiencies of factor X are uncommon and in isolation are seen most frequently in patients with amyloidosis and in association with upper respiratory tract infections.
Treatment of the deficiency state involves factor X replacement with either fresh frozen plasma or prothrombin complex concentrates. However, the latter may be associated with an increased risk of thrombosis.     

FIBRILLARY GLOMERULONEPHRITIS – A REPORT OF TWO CASES

Two patients with an uncommon form of glomerulonephritis are described. The main clinical features were hematuria and proteinuria associated with normal renal function. The glomerular lesions consisted of mesangial hypercellularity and capillary wall thickening. Immunofluorescence was positive for IgG and C3 in both cases. Widespread deposition of microfibrils (mean diameters 17.0 nm and 18.4 nm) within mesangial areas and capillary basement membranes was seen on electron microscopy. Congo red staining for amyloid was negative. In both patients there was no evidence of underlying disease or extra-glomerular involvement and hence the disorder appeared to represent a primary glomerulonephritis.     

The Impact of Diabetes Mellitus on Two-Year Mortality Following Contemporary Percutaneous Coronary Intervention: Implications for Revascularization Practice

Objective: To assess the impact of diabetes on 2-year mortality in current PCI practice.
Background: In patients with coronary artery disease undergoing revascularization, diabetes mellitus is associated with higher mortality.
Methods: A retrospective analysis was done of all patients undergoing PCI at our tertiary center between January 2000 and December 2004. There were 6,160 PCI procedures performed in 5,759 patients who received at least one stent. Of these patients, 801 (13.9%) were diabetic and 4,958 (86.1%) were nondiabetic. The primary outcome measure of the study was all-cause mortality. All patients were followed up for a period of 2 years. Multivariate logistic regression analysis was used to test for a potential independent association between diabetic status and follow-up mortality.
Results: Before adjustment, a trend toward higher mortality was observed in diabetic patients compared to non-diabetics at 1 year (3.2% vs 2.4%) and 2 years (5.1% vs 3.8%), P = 0.12. Independent predictors for mortality were increasing age, renal dysfunction, peripheral vascular disease, NYHA class >2, urgent PCI, treating left main stem lesions, vessel diameter ≤ 2.5 mm, and 3-vessel disease. The use of drug-eluting stent was associated with a reduction in mortality. Diabetes was found to have no independent impact on mortality following PCI (odds ratio = 1.08; 95% confidence intervals = 0.73–1.60; P = 0.71).
Conclusion: The presence of diabetes was not an independent predictor of mortality following PCI. A diabetic patient that does not require insulin treatment and has no evidence of macro- or microvascular diabetic disease could enjoy a PCI outcome similar to nondiabetic subjects.