The association of floppy mitral valve with disjunction of the mitral annulus fibrosus

Floppy mitral valve is usually attributed to connective-tissue degeneration. However, we have observed several instances in which both a floppy mitral valve and an abnormal mitral annulus fibrosus were present at autopsy. To study this association, we examined 900 hearts (after postmortem arteriography and fixation in distention) from autopsies of adults at The Johns Hopkins Hospital. Twenty-five (3 percent) of the hearts had a morphologically typical floppy mitral valve; in 23 of them (92 percent), the mitral annulus fibrosus showed disjunction--i.e., a separation between the atrial wall-mitral valve junction and the left ventricular attachment. In 42 other hearts (5 percent), which were from significantly younger patients (mean age [+/- SE], 60 +/- 2 years vs. 68 +/- 3; P less than 0.05), there was mitral annulus disjunction but no floppy mitral valve. Two hearts had a floppy mitral valve but no disjunction of the annulus; both of them had old infarcts of the papillary muscle. Our results show that floppy mitral valve is significantly associated with disjunction of the mitral annulus fibrosus (P less than 0.001). We suggest that floppy mitral valve develops from hypermobility of the valve apparatus, and that it is usually secondary to disjunction of the mitral annulus fibrosus, an anatomic variation in the morphology of the annulus.     

Body temperature is elevated in the early postmortem period

During the collection of specimens at autopsy for biochemical analysis, it was observed that body temperatures were higher than expected. To evaluate this observation further, rectal temperatures were determined at the earliest feasible time after death in 20 adult patients for whom recent premortem rectal temperatures were available for comparison. The average premortem temperature was 37.6 degrees C (range, 34.9 to 41.1 degrees C) and had been obtained 19 to 240 minutes (average, 107 minutes) before death. The average postmortem temperature, also 37.6 degrees C (range, 35.5 to 41.3 degrees C), was obtained 116 to 401 minutes (average, 202 minutes) after death. In the 11 patients in whom the postmortem interval was less than three hours (average, 155 minutes), there was an average postmortem temperature increase of 0.5 degree C (range, +1.3 to -0.7 degree C). The results suggest that there is usually an initial postmortem elevation in body temperature as measured rectally, probably as a result of continuing tissue and bacterial metabolism in the absence of the usual heat-dispersal mechanisms. This phenomenon should be considered when postmortem materials are used for analysis or when postmortem interval is determined by body temperature.     

Sexual discordance in monozygotic twins

We report on monozygotic (MZ) twins who were discordant for phenotypic sex and Ullrich-Turner syndrome (UTS). The nonviable female was hydropic with cystic hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia, intestinal malrotation, and small ovaries. The male was phenotypically normal. The monochorionic, diamniotic placenta had hydropic changes limited to the UTS infant's side. Skin samples from the infants and blood from their parents were obtained for cytogenetic and molecular analysis. Karyotypes of the twins were 45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8 loci showed complete identity. MZ twins discordant for phenotypic sex have been described previously. Most of these show evidence of mosaicism in a 45,X patient with a normal 46,XY cell line, and a normal 46,XY male. While the issue of mosaicism in our case cannot be fully resolved, no mosaicism was found in 50 cells analyzed cytogenetically from each culture or by PCR analysis of a Y-specific sequence. The twins probably originated from either postzygotic nondisjunction or anaphase lag, followed or accompanied by twinning. The discordant placental morphology suggests an embryonic origin of at least part of the placental mesenchymal core.     

Catenoidal shape of the interventricular septum acquired secondary to myocardial infarction

A catenoidal, or saddle-shaped, configuration of the interventricular septum, concave toward the left ventricular cavity in the transverse plane, but convex toward the left ventricular cavity in the apex to base plane, occurs in idiopathic hypertrophic subaortic stenosis and possibly may lead to septal hypertrophy and immobility. The authors also have observed catenoidal shape of the interventricular septum in hearts with myocardial infarcts. They reviewed 1,415 hearts examined after postmortem arteriography and fixation in distention from patients autopsied at The Johns Hopkins Hospital. Among 586 hearts with myocardial infarcts, there were 54 (9%) with a catenoidal shape of the interventricular septum. The infarcts, 45 anterior septal and 9 inferior and lateral, appeared to account for the reversal of normal apex to base curvature, although coexistent idiopathic hypertrophic subaortic stenosis could not be excluded in 3 patients. There was moderate or marked infarct expansion in 25/54 (46%) and septal or free wall rupture in 8 (15%) hearts. Reduced average net septal curvature in the 54 hearts, highly significant compared with that in 80 hearts without infarcts (P less than 0.001), would reduce the septum's contribution to left ventricular function and may contribute to the observed postinfarct congestive failure, 30/54 (56%), and hypoperfusion, 7/54 (13%). The results suggest that some myocardial infarcts may produce a catenoidal shape of the interventricular septum that could reduce the functional activity of the surviving uninfarcted basilar portion of the septum and thereby contribute to postinfarction cardiac dysfunction.     

A microcirculatory technique for evaluating intravascular and topical administration of vasoactive agents: Response to AVP in the SHR

A "closed bath" cremaster muscle preparation is described which permits the administration of vasoactive materials to the microvasculature via intraarterial injection and topical suffusion. The technique is evaluated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by comparing arteriolar responses to intraarterial and topically suffused arginine vasopressin. The preparation utilizes a thermostatically heated brass suffusion chamber overlying the cremaster. The chamber is closed with a glass coverslip. Experimental materials are presented to the microvessels via intraarterial injection or suffusion through the chamber. The coverglass permits high optical resolution with both routes of administration. Following vasopressin administration, changes in arteriolar diameter were continuously monitored by image-shearing techniques or variable-resistance calipers. The responses were analyzed by comparing both the peak 5-sec vasoconstriction and a 60-sec integrated response. Intraarterial and topical suffusion of vasopressin (1.25 X 10(-10)-3.75 X 10(-7) M) caused dose-dependent vasoconstriction among 23-microns arterioles. Compared to the WKY, vasoconstriction was greater in the SHR when vasopressin was administered intraarterially. A similar strain difference was not observed with topical suffusion. The dose-response curves with intraarterial vasopressin were shifted approximately 100-fold in concentration to the right relative to those with topically suffused vasopressin. The "closed bath" cremaster muscle preparation described has several distinct advantages: (1) it permits introduction of different vasoactive materials in the most physiological manner in the same animal, and (2) it maintains high optical resolution and clarity for critical observation of the smallest vessels, even with suffusion.     

Lymph Node Tumor Volumes in Patients Undergoing Sentinel Lymph Node Biopsy for Cutaneous Melanoma

Background: Regional lymph node tumor volumes in patients undergoing sentinel lymph node (SN) biopsy (SNB) for treatment of cutaneous melanoma have not been described. The objectives of this study were to describe the lymph node tumor volumes typically seen in this population and to correlate tumor volumes with tumor thickness and positive SN characteristics.Methods: Review of a consecutive series of patients with clinically localized cutaneous melanoma who underwent SNB of nonpalpable regional lymph node basins followed by complete lymphadenectomy (LND) was performed. Multiple lymph node sections from positive SNs and nonsentinel nodes (NSNs) in LND specimens were examined microscopically. Individual tumor deposit diameters were measured using an ocular micrometer. Aggregate tumor volumes were calculated for SN and LND specimens. Tumor volumes and SN and LND positivity rates were correlated with tumor thickness, the number of positive SNs, and the presence of multiple SN tumor deposits.Results: SNB procedures were performed for 149 melanomas in 189 regional nodal basins. The mean tumor depth was 2.48 mm. The mean number of SNs/basin was 2.1. Thirty-two of 149 SNB procedures (21.5%) revealed a total of 34 nodal basins with at least one positive SN. The median tumor volume in positive SNs was 4.7 mm³ (range, 0.1-3618 mm³; mean, 209 mm³). The median aggregate tumor volume in positive LND specimens was 4.9 mm³ (range, 0.1-3618 mm³; mean, 224 mm³). Six basins (17.6%) contained at least one positive NSN. The regional node aggregate tumor volume correlated weakly with tumor thickness (Pearsons correlation coefficient = .302, P = .0934). NSN positivity was not predicted by tumor thickness, American Joint Committee on Cancer tumor stage, number of positive SNs, or number of metastatic deposits within SNs.Conclusions: Most melanoma-positive SNs contain minute tumor volumes. Tumor thickness and patterns of SN metastases may not be predictive of tumor burden or the presence of positive NSNs.     

Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women.

Flaxseed, the richest known source of plant lignans, has been shown to have chemoprotective effects in animal and cell studies. Some of its effects may be mediated through its influence on endogenous hormone production and metabolism. Two competing pathways in estrogen metabolism involve production of the 2-hydroxylated and 16 alpha-hydroxylated metabolites. Because of the proposed differences in biological activities of these metabolites, the balance of the two pathways has been used as a biomarker for breast cancer risk. We examined the effects of flaxseed consumption on urinary estrogen metabolite excretion in postmenopausal women. Twenty-eight postmenopausal women were studied for three seven-week feeding periods in a randomized crossover design. During the feeding periods, subjects consumed their usual diets plus ground flaxseed (0, 5, or 10 g/day). Urinary excretion of the estrogen metabolites 2-hydroxyestrogen (2-OHEstrogen) and 16 alpha-hydroxyestrone (16 alpha-OHE1) as well as their ratio, 2/16 alpha-OHE1, was measured by enzyme immunoassay. Flaxseed supplementation significantly increased urinary 2-OHEstrogen excretion (p < 0.0005) and the urinary 2/16 alpha-OHE1 ratio (p < 0.05) in a linear, dose-response fashion. There were no significant differences in urinary 16 alpha-OHE1 excretion. These results suggest that flaxseed may have chemoprotective effects in postmenopausal women.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Binding of psychotropic drugs to isolated alpha-acid glycoprotein

Alpha1-acid glycoprotein (alpha1-AG) was purified from human sera, and its binding properties with respect to psychotropic drugs were examined by equilibrium dialysis methods in order to clarify the specificity of binding. Radioactive imipramine, a tricyclic antidepressant, was used as the primary ligand. Other drugs, representative of different classes, were tested as potential inhibitors of the alpha1-AG-imipramine binding. The K(a) for imipramine was 2.8 x 10(5) (+/- 0.8) M(-10 (mean +/- S.D.). Chlorpromazine, fluphenazine, thioridazine, loxapine and thiothixene, which are antipsychotic drugs, were competitive inhibitors of imipramine binding, and their K(a) values were in the same range. Propranolol, haloperidol and diazepam were also competitive inhibitors but their affinities were lower. Molindone, an indolic antipsychotic, when tested at the same concentrations as the other drugs, did not affect imipramine binding. Trihexyphenidyl, an anti-Parkinson drug, was a potent but noncompetitive inhibitor. These data identify the antidepressant and major tranquilizer drugs that exhibit high affinity for alpha1-AG and indicate that alpha1-AG may account for 40 per cent of total imipramine bound in serum. Since in psychiatric clinical practice two drugs are frequently administered together, possible competitive effects are discussed as well as the potential role of alpha1-AG in psychiatric illness.     

Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil

We have used a remifentanil-based anaesthetic for patients undergoing major abdominal surgery who would normally have gone to the intensive care unit in this hospital. Avoiding intensive care unit admission was considered an advantage as a shortage of intensive care unit beds was leading to the cancellation of operations. We first used remifentanil as part of a safety and efficacy study. The aim was to see if the rapid and complete awakening obtained when using this drug would allow us to avoid the need for admission to an intensive care unit and use a high dependency unit instead. This was shown to be practicable. In comparison with a group of patients matched retrospectively for the type of operation before remifentanil was used there was a reduction in the length of time (mean+/- SD) patients' lungs were ventilated (612+/-417 vs. 9.9+/-28.9 min P< 0.0001). There was no saving in cost ( pound808.71+/- pound187.06 vs. pound795.27+/- pound253.49). When remifentanil was used routinely (after the safety and efficacy study), there were significant reductions in the time to tracheal extubation (612+/-417 vs. 4+/-10 min P < 0.0001) and costs (808.71I vs. 392.10 I P < 0.0001) compared with other patients in whom it was not used. Patients waiting for a liver transplant were also being cancelled when a donor organ became available because of the shortage of intensive care unit beds. Based on our other experience with remifentanil, we used a similar anaesthetic technique for these patients. It proved possible to extubate the trachea in 12 of 15 patients at the end of the operation. No patient needed re-intubation. The need for intensive care and therefore cancellation of surgery was reduced. In contrast, only one patient's trachea was extubated immediately after surgery in the group of patients anaesthetized before the introduction of remifentanil. A remifentanil-based technique in combination with a change in organization has therefore enabled us to avoid admission to the intensive care unit for these patients.