Three-dimensional echocardiographic assessment of annular shape changes in the normal and regurgitant mitral valve.

OBJECTIVES: To compare mitral annular shape and motion throughout the cardiac cycle in patients with normal hearts versus those with functional mitral regurgitation (FMR). BACKGROUND: The causes of mitral regurgitation without valvular disease are unclear, but the condition is associated with changes in annular shape and dynamics. Three-dimensional (3D) imaging provides a more comprehensive view of annular structure and allows accurate reconstructions at high spatial and temporal resolution. METHODS: Nine normal subjects and 8 patients with FMR undergoing surgery underwent rotationally scanned transesophageal echocardiography. At every video frame of 1 sinus beat, the mitral annulus was manually traced and reconstructed in 3D by Fourier series. Annular projected area, nonplanarity, eccentricity, perimeter length, and interpeak and intervalley spans were determined at 10 time points in systole and 10 points in diastole. RESULTS: The mitral annulus in patients with FMR had a larger area, perimeter, and interpeak span than in normal subjects (P <.001 for all). At mid-systole in normal annuli, area and perimeter reach a minimum, nonplanarity is greatest, and projected shape is least circular. These cyclic variations were not significant in patients with FMR. Annular area change closely paralleled perimeter change in all patients (mean r = 0.96 +/- 0.07). CONCLUSIONS: FMR is associated with annular dilation and reduced cyclic variation in annular shape and area. Normal mitral valve function may depend on normal annular 3D shape and dimensions as well as annular plasticity. These observations may have implications for design and selection of mitral annular prostheses.

Chloride is an allosteric effector of copper assembly for the yeast multicopper oxidase Fet3p: an unexpected role for intracellular chloride channels.

GEF1 is a gene in Saccharomyces cerevisiae, which encodes a putative voltage-regulated chloride channel. gef1 mutants have a defect in the high-affinity iron transport system, which relies on the cell surface multicopper oxidase Fet3p. The defect is due to an inability to transfer Cu+ to apoFet3p within the secretory apparatus. We demonstrate that the insertion of Cu into apoFet3p is dependent on the presence of Cl-. Cu-loading of apoFet3p is favored at acidic pH, but in the absence of Cl- there is very little Cu-loading at any pH. Cl- has a positive allosteric effect on Cu-loading of apoFet3p. Kinetic studies suggest that Cl- may also bind to Fet3p and that Cu+ has an allosteric effect on the binding of Cl- to the enzyme. Thus, Cl- may be required for the metal loading of proteins within the secretory apparatus. These results may have implications in mammalian physiology, as mutations in human intracellular chloride channels result in disease.

The late chlamydial inclusion membrane is not derived from the endocytic pathway and is relatively deficient in host proteins.

Chlamydiae are obligate intracellular parasites which multiply within infected cells in a membrane-bound structure termed an inclusion. Newly internalized bacteria are surrounded by host plasma membrane; however, the source of membrane for the expansion of the inclusion is unknown. To determine if the membrane for the mature inclusion was derived by fusion with cellular organelles, we stained infected cells with fluorescent or electron-dense markers specific for organelles and examined inclusions for those markers. We observed no evidence for the presence of endoplasmic reticulum, Golgi, late endosomal, or lysosomal proteins in the inclusion. These data suggest that the expansion of the inclusion membrane, beginning 24 h postinoculation, does not occur by the addition of host proteins resulting from either de novo host synthesis or by fusion with preexisting membranes. To determine the source of the expanding inclusion membrane, antibodies were produced against isolated membranes from Chlamydia-infected mouse cells. The antibodies were demonstrated to be solely against Chlamydia-specified proteins by both immunoprecipitation of [35S]methionine-labeled extracts and Western blotting (immunoblotting). Techniques were used to semipermeabilize Chlamydia-infected cells without disrupting the permeability of the inclusion, allowing antibodies access to the outer surface of the inclusion membrane. Immunofluorescent staining demonstrated a ring-like fluorescence around inclusions in semipermeabilized cells, whereas Triton X-100-permeabilized cells showed staining throughout the inclusion. These studies demonstrate that the inclusion membrane is made up, in part, of Chlamydia-specified proteins and not of existing host membrane proteins.

Nucleotide polymorphism at the xanthine dehydrogenase locus in Drosophila pseudoobscura.

Sequential polyacrylamide electrophoresis has revealed 20 allozymes of xanthine dehydrogenase (XDH) in Drosophila pseudoobscura. DNA sequence determination of seven isolates of the Xdh locus that represent six allozyme classes are presented here. Of the 5,456 sites examined, 180 are polymorphic, with 27 polymorphisms occurring at nonsynonymous, or replacement, sites. An average of nine amino acids differ between XDH allozyme classes, with 85% of the polymorphic amino acids singly represented. The level and pattern of variation observed at Xdh argue that the effective population size of the species is quite large--i.e., on the order of 2 x 10(6)--and that the populations sampled are quite ancient. In addition, as judged by two statistical tests, the levels of nucleotide polymorphism observed at Xdh are compatible with predictions from the neutral theory of molecular evolution.

Abnormally high level of C4b binding protein and deficiency of free fraction of protein S in a patient with systemic lupus erythematosus and recurrent thromboses.

A patient with systemic lupus erythematosus and numerous thrombotic accidents was found to have a deficiency of the free fraction of protein S, most likely due to an abnormally high level of C4b binding protein. These abnormalities, unique in comparison to 4 other patients with hypercoagulation states, were partially corrected with cyclophosphamide. There was no evidence of a consumption of complement components. The interactions between the hemostasis system and the complement cascade are discussed.

Neuromuscular organization of the pectoralis (pars thoracicus) of the pigeon (Columba livia): implications for motor control.

The pectoralis (pars thoracicus) of the domestic pigeon (Columba livia) is divisible into two anatomical parts, the pars sternobrachialis (SB) and the pars thoracobrachialis (TB). Innervation to this complex is from rostral and caudal branches of the brachial ventral cord. In four anesthetized pigeons, the distribution of muscle units associated with each nerve branch was mapped after prolonged stimulation of each nerve and subsequent analysis for muscle fiber glycogen. An additional three animals were used to analyze the morphology, distribution, and histochemical profiles of the muscle fibers in the SB and TB subregions. Fibers were characterized on the basis of their reactions for myofibrillar adenosine triphosphates (alkaline and acid preincubation) and reduced nicotinamide adenine dinucleotide diaphorase (NADH-D). The SB is primarily innervated by the rostral nerve branch and the TB by the caudal nerve branch. For two-thirds of the muscle's length, the SB is separated from the TB by an aponeurosis, the membrana intermuscularis (MI). SB and TB fibers located posteroventral to the caudal margin of the MI are innervated variously by both nerves. Two populations of fibers were recognized, distinguishable primarily by 1) fiber diameter and 2) density of the NADH-D reaction product. Compared to the TB, the SB possesses a higher average percentage of large fibers. Within the SB but not the TB the percentage of large fibers increases from deep to superficial. These data support our previous findings that the pars thoracicus of the pigeon is partitioned into at least two functional subunits, each with a potential for independent action on the wing during flight.

Urate-mediated inflammation in nodal osteoarthritis: clinical and roentgenographic correlations.

We studied 25 patients with crystal-proven gout or roentgenographic evidence of gouty arthritis, or both, in finger joints involved with nodal osteoarthritis (OA). These patients were elderly (mean age 71.4 years), and 72% of them were receiving diuretic therapy. Roentgenographic findings, in addition to features typical of OA, included soft tissue densities (tophi), with or without calcification, large intraarticular erosions, characteristic nonmarginal cortical erosions, and periarticular osteolysis. We conclude that urate crystals mediate episodes of acute inflammation in certain patients with nodal OA. This association is noted primarily in elderly patients of both sexes, especially in those receiving diuretic therapy.

Severe aortic stenosis in systemic lupus erythematosus and mucopolysaccharidosis type II (Hunter's syndrome).

Cardiac manifestations of the mucopolysaccharidoses often include valvular regurgitation, but stenotic lesions are quite rare. This report describes a 30-year-old man with mucopolysaccharidosis type II (Hunter's syndrome) and systemic lupus erythematosus who developed severe progressive aortic stenosis and died. Autopsy examination revealed evidence of various cardiac mucopolysaccharide disease including valvular leaflets thickened and distorted with fibrocalcific nodules. A brief review of previously reported valvular disease in Hunter's syndrome and other mucopolysaccharidoses is presented. This is also the first report of a patient with both systemic lupus and a mucopolysaccharidosis.

Progressive systemic sclerosis: mode of presentation, rapidly progressive disease course, and mortality based on an analysis of 91 patients.

The overwhelming majority of patients with PSS present with combinations of Raynaud's phenomenon, sclerodactyly, polyarthralgias, or swelling of an extremity. However, the clinical presentation of PSS may be atypical; 14% of patients in the present series initially sought medical attention for symptoms other than Raynaud's phenomenon, tight skin, or joint pain. In the present series, only 31% of patients fulfilled the ARA criteria for PSS at the time of initial medical evaluation. Most patients manifested advanced disease by the time the criteria were fulfilled. The ARA criteria for the classification of PSS appear to have limited value with regard to making the diagnosis in an individual patient. Rapidly progressive PSS occurred in 17.6% of patients in this series and represents a particularly fulminant form of the disease whose course may not be predictable on clinical grounds at the time of initial medical evaluation or diagnosis. Patients destined to develop renal or cardiorespiratory failure usually do so in the first 3 years of disease. Close observation of PSS patients during the first 12 to 18 months may serve to identify those individuals who will undergo an accelerated disease course. Prognosis for patients with rapidly progressive PSS is poor and is associated with significantly higher mortality compared with patients with a more protracted disease course. Future therapeutic trials in PSS should be designed with the recognition that a subgroup of patients with this disorder will have a rapidly progressive disease course.

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

Nd-YAG laser applications in surgical endoscopy: a single center comprehensive experience.

A retrospective review of endoscopic procedures using the Nd-YAG laser was carried out for patients treated between September 1984 and November 1986. Two hundred twenty two procedures were performed on 104 patients (58M:46W) during this 26 month period. The study encompasses a unique period of time in this center, as it includes the initial use of the endoscopic laser technique, the learning curves associated with its application, and finally, the time when its use became routine. Treatment of tumors was the indication in 47 per cent of the cases. Gastrointestinal bleeding of benign cause was the indication in nearly half of the patients; arteriovenous malformations were the most common causes of bleeding. Laser photocoagulation of hemorrhoids was performed in 11 cases. Upper endoscopy was the route in 33 per cent of procedures. Anoscopy, flexible sigmoidoscopy, and colonoscopy were the routes in the remainder. The time spent on the procedure and the energy delivered were found to be variables of the type of lesion and the endoscopic route. Nd-YAG laser endoscopy can be used safely and effectively for a variety of bleeding and obstructive gastrointestinal conditions. Appropriate certification for granting of privileges to laser endoscopists is of utmost importance.

A functional analysis of the primary upstroke and downstroke muscles in the domestic pigeon (Columba livia) during flight.

In domestic pigeons (Columba livia), the electrical activity of the major depressor muscle of the wing, the pectoralis (pars thoracicus), beings in late upstroke well before the wing begins its downstroke excursion. The two architecturally distinct heads of the pectoralis, the sternobrachialis and the thoracobrachialis, are differentially recruited during take-off, level flight and landing. In addition to wing depression, the sternobrachialis protracts the humerus and the thoracobrachialis retracts the humerus. At the point of transition from wing upstroke to downstroke, the pectoralis EMG signal typically exhibits a reduction in amplitude. The supracoracoideus, in addition to an expected EMG associated with wing elevation, is co-activated with the pectoralis about 50% of the time.

Structure and neural control of the pectoralis in pigeons: implications for flight mechanics.

The pectoralis muscle in pigeons (Columba livia) is composed of two heads (sternobrachialis, thoracobrachialis) that are separately innervated and have different fiber orientations. High-speed film and electromyographic studies of free-flying pigeons reveal that the pectoralis is activated prior to wing depression (the power stroke) and that its two heads are differentially recruited during takeoff, level flight, and landing. The electrical activity patterns of both heads support an interpretation that intramuscular elasticity provides energy storage. The pectoralis is not only the prime wing depressor but is also capable of adjusting the excursion of the wing during different phases of flight.

Gold lung: recent developments in pathogenesis, diagnosis, and therapy.

Gold lung is a hypersensitivity pneumonitis to gold-containing compounds. It can be distinguished from rheumatoid lung by its subacute or acute onset, diffuse interstitial and/or alveolar filling pattern on chest roentgenogram, presence of lymphocytes on BAL with an inverse helper/suppressor ratio, and response to withdrawal of gold and/or corticosteroid therapy. Other in vitro assays of gold hypersensitivity using peripheral blood lymphocytes are only sporadically positive and, therefore, of limited value in making the diagnosis. Physicians prescribing organic gold compounds should elicit pulmonary complaints throughout the duration of therapy. When patients receiving gold therapy present with signs and symptoms consistent with an acute or subacute hypersensitivity pneumonitis, the gold therapy should be withheld and a diagnostic workup initiated.

Neodymium-YAG laser. A new palliative tool in the treatment of colorectal cancer.

Twenty-four patients with colorectal carcinoma and one patient with a recurrent, transitional-cell, vesical tumor invading the rectum but not amenable to surgical resection underwent neodymium-YAG laser therapy. There were 16 men and nine women with an average age of 75.6 years (range, 35 to 93 years). There were 14, 6, 1, 1, and 3 tumors found in the rectum, rectosigmoid colon, transverse colon, descending colon, and ascending colon, respectively. Symptoms consisted of bleeding or partial obstruction. Twelve patients were high-risk surgical candidates, 11 patients had widespread disease, and two patients had another primary tumor not controlled by a previous surgical procedure. The tumor was eradicated in two patients. There were two complications, namely, a perforation and a rectovaginal fistula. Thirteen patients died from their disease. The remaining patients have been kept free from obstruction and bleeding.

The clinical spectrum of gouty arthritis in women.

We reviewed crystal-proved gouty arthritis in 23 women. Twenty-one (91%) developed gout after menopause onset. Tophaceous gout occurred in six (26%), polyarticular involvement in 13 (57%); 70% manifested an underlying arthropathy, usually osteoarthritis. We studied 75 men with crystal-proved gout for comparison. Women developed gout significantly later compared with men, more often were receiving diuretics before gout onset, and more frequently manifested renal insufficiency and monoarticular involvement. These differences were significant when controlled for the women's later age at onset. Significantly more men than women had alcoholism and an identifiable precipitating event for acute attacks. There were no significant differences in race, age, family history of gout, disease duration, hypertension, distribution of joint involvement, tophi, or mean serum urate concentration. Gout in women is overwhelmingly postmenopausal, apparently associated with diuretic therapy and renal insufficiency independent of the effects of age. Articular characteristics in men and women are remarkably similar.