Regional coronary vasoconstriction after combined beta-adrenergic and calcium channel blockade in patients with coronary artery disease

The beta-adrenergic and calcium channel blocking drugs, which individually and combined have proven efficacious in the treatment of angina pectoris, appear to have opposing effects on coronary artery vasomotion. Previous studies have shown that beta-adrenergic blockade may potentiate and calcium channel blockade reverse coronary vasoconstriction during adrenergic cold stimulation in patients with coronary artery disease. To assess the coronary hemodynamic effects of combined drug therapy, thermodilution coronary sinus and great cardiac vein flow and mean arterial pressure were measured during serial cold pressor testing, both before and after 0.1 mg/kg of intravenous propranolol and again after the addition of 10 mg of sublingual nifedipine in 21 patients (9 without [group A1] and 12 with [group A2] greater than 50% narrowing of the left anterior descending coronary artery). In an additional 15 patients (6 patients without [group B1] and 9 with [group B2] left anterior descending artery stenosis), serial cold pressor testing was performed reversing the drug order. Despite significant increases in mean arterial pressure (p less than 0.01) during cold pressor testing, coronary sinus resistance responses after propranolol plus nifedipine were not statistically significant for any group. However, regional coronary resistance responses differed between patients with and without left anterior descending artery stenosis. In group A1, great cardiac vein resistance was unchanged after propranolol plus nifedipine. In group A2, great cardiac vein flow decreased significantly after propranolol plus nifedipine from 8 +/- 17 to -4 +/- 12% (p less than 0.01 versus control), and great cardiac vein resistance increased from 4 +/- 21 to 15 +/- 19% (p less than 0.01 versus control). A similar significant response was observed for groups B1 and B2. Regional coronary vasoconstriction during adrenergic stimulation after combined drug therapy was only observed in patients with significant left anterior descending artery stenosis. These data suggest that in some patients with severe coronary artery disease, combined beta-adrenergic and calcium channel blockade modified regional coronary responses to adrenergic stimulation with an inhomogeneous distribution of blood flow to potentially ischemic regions without affecting total coronary blood flow. These data also imply that an improvement in anginal symptoms after combined drug therapy may be due primarily to mechanisms that reduce myocardial oxygen demand rather than to improved myocardial oxygen supply.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man.

The genes for four components (C) of complement in the human major histocompatibility complex (HLA) have been aligned previously in a series of overlapping cosmid cloned inserts. Those inserts, which contained the two C4 genes C4A and C4B, hybridized with human adrenal mRNA, indicating that they contain a gene expressed in the adrenal. The mRNA fraction of 2.4 kilobases (kb) hybridizes with genomic DNA of 4.5 kb, which is duplicated and lies about 1.5 kb 3' of both the C4A and the C4B complement genes. Sequencing of a 430-base section and comparison with the published cDNA sequence of bovine cytochrome P-450 21-hydroxylase, peptide sequences of porcine 21-hydroxylase, and a cDNA sequence of a rat liver cytochrome P-450 identified the gene as coding for human steroid 21-hydroxylase [steroid,hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10]. Mapping of the gene was helped by use of a synthetic oligonucleotide based on the bovine cDNA sequence.     

Cardiac arrhythmias in patients with surgical repair of Ebstein's anomaly

Preoperative, perioperative and postoperative arrhythmias in 52 consecutive patients who underwent operation for Ebstein's anomaly were reviewed. There were 25 male and 27 female patients (mean age 18 years, range 11 months to 64 years). Thirty-four patients had one or more documented arrhythmias preoperatively (18 had paroxysmal supraventricular tachycardia, 10 had paroxysmal atrial fibrillation or flutter, 13 had ventricular arrhythmia and 3 had high grade atrioventricular block). Seven patients without documented arrhythmias had a history typical of tachyarrhythmias. During the perioperative and early postoperative periods, 14 patients had atrial tachyarrhythmias and 8 had ventricular tachycardia or ventricular fibrillation. There were seven deaths between day 1 and 27 months after operation. Five of these deaths were sudden (all in male patients, aged 12 to 34 years), and four of the patients had had perioperative ventricular tachycardia or ventricular fibrillation. One patient was taking one antiarrhythmic agent and another patient was taking two at the time of sudden death. Of the 18 patients with paroxysmal supraventricular tachycardia and 9 patients with paroxysmal atrial fibrillation or flutter preoperatively who were followed up for a mean of 40 and 36 months, respectively, 22 and 33% continued to have symptomatic tachycardia. Of the 11 patients (mean age 9 years) without preoperative documentation or symptoms of arrhythmia, follow-up data were obtained (range 1 to 144 months, mean 31) in 9 patients. None died suddenly or developed symptomatic arrhythmia.     

Coding nucleotide sequence of rat NADPH-cytochrome P-450 oxidoreductase cDNA and identification of flavin-binding domains.

The coding nucleotide sequence of the mRNA for NADPH-cytochrome P-450 oxidoreductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) from rat liver was determined from two overlapping cDNA clones, pOR-7 and pOR-8, which together contain 2401 nucleotides complementary to rat liver oxidoreductase mRNA. The single open reading frame of 2034 nucleotides spanning these cDNAs codes for a 678 amino acid polypeptide with a molecular weight of 76,962. The deduced amino acid composition is in excellent agreement with that determined by direct amino acid analysis of purified rat liver P-450 oxidoreductase, and the amino-terminal region (residues 1-80) largely coincides with the amino-terminal sequence of the oxidoreductase isolated from rabbit liver. Comparison of the amino acid sequence to those of other flavoproteins revealed two separate domains that are likely to be involved in flavin binding: a long segment (residues 77-228) homologous with Desulfovibrio vulgaris flavodoxin, an FMN-containing protein, and a shorter segment (residues 452-477) homologous with the FAD-binding segment of fumarate reductase from Escherichia coli.     

A New Intraoperative Syndesmosis Instability Classification System: Utility and Medium‐term Results in Closed Displaced Ankle Fractures

Objective

To investigate the utility and medium‐term results of a new intra‐operative classification system for distal tibiofibular syndesmosis injury in ankle fractures.

Methods

Between January 2010 and January 2015, 116 patients diagnosed with displaced closed Weber B and C ankle fractures were treated in our department. The etiology of injury was 56 cases of fall‐sprain, 36 of traffic injury, 14 of fall from a height, and 10 of multiple injuries. After fixation of the fibular fracture, we classify syndesmosis stability as either normal or one of three grades of instability using the fibular hook traction test. This determined further fixation selection and final syndesmosis treatment.

Results

Of 116 cases, 82 (71%) demonstrated a tibiofibular syndesmosis injury and 52 (45%) were unstable. Twenty‐six cases were type I injuries (<4 mm displacement), 41% cases were type II injuries (4–7 mm displacement), and 3% of cases were type III injuries (>7 mm displacement). Types II and III are defined as unstable and require stabilization. Type III injuries have multiplanar instability and require two screws at the syndesmosis. Weber C fractures demonstrate significantly greater degrees of instability than Weber B fractures (χ² = 15.50, P = 0.0014). All patients were followed up for 12–24 months, with no cases of non‐union or broken screws. Good and excellent results were achieved in 93% of cases (according to the American Orthopaedic Foot and Ankle Society scoring system).

Conclusion

The syndesmosis instability classification system provides a rational and efficient basis for managing syndesmosis instability. Our results from application of the algorithm justify its further evaluation in the treatment of patients with closed displaced Weber B and C ankle fractures.

     

Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan

Purpose

To validate and compare the values of “MIC” and “trifecta” as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN.

Methods

We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow-up renal scan 3–6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta.

Results

Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B ?1.8 (?2.7, ?0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation.

Conclusions

Achievement of both MIC and “trifecta” is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney.

     

Increasing the number of biopsy cores improves the concordance of biopsy Gleason score to prostatectomy Gleason score

OBJECTIVE: To evaluate taking more biopsy cores for predicting the radical prostatectomy (RP) Gleason score compared with the biopsy Gleason score, as although random sextant biopsies are the standard for a tissue diagnosis of prostate cancer, and taking more biopsies increases the detection rate, it is uncertain whether taking more cores improves the prediction of the RP Gleason score. PATIENTS AND METHODS: We analysed retrospectively 404 patients from three centres (Seattle 162, Washington 107 and Chicago 135) who had RP for prostate cancer. Six, eight or 10 biopsies were taken based on the physician's preference and the patient's characteristics. RESULTS: Before RP, 158 (39%) patients had six, 65 (16%) had eight and 181 (45%) had 10 biopsy cores taken. The accuracy of the Gleason sum of the three groups was 65/158 (41%), 26/65 (40%) and 104/181 (57.5%), respectively (P < 0.004, 10-core vs six-core). However, when comparing the Gleason score separately (i.e. 4 + 3 is not equal to 3 + 4), the accuracy of the three groups was 48/158 (30%), 20/65 (31%), and 95/181 (52.5%), respectively (P < 0.001, 10-core vs six core). CONCLUSIONS: Taking more biopsy cores improves the accuracy of the biopsy Gleason score in predicting the final Gleason score at RP; the predictive accuracy of the final Gleason score may be increased from 41% to 58% by increasing the number of biopsies from six to 10.