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Functional outcome was evaluated in 40 patients with a diagnosis of soft tissue sarcoma (STS), who had received wide local surgical excision and postoperative radiation therapy. All patients were two or more years postsurgical excision, and 1.75 or more years postradiation. Patients were separated into three anatomic groups: head, neck, or trunk (HNT); lower extremity (LE); and upper extremity (UE). Each patient was assessed for range of motion, muscle strength, edema, pain, activities of daily living (ADL), and vocational changes. There was significantly more (p = 0.037) edema in patients with LE lesions than in patients in either of the other groups. Patients with LE lesions had greater difficulty with ADL and mobility than those with UE or HNT lesions (p = 0.019), and vocational changes were more frequent (p = 0.055). Patients with lower extremity STS are at higher risk for developing disability than patients with STS at other anatomic sites.

Pro-opiocortin was purified from camel pituitaries by procedures including high-performance liquid chromatography. The precursor relationship of the pure protein to the opioid peptides and to corticotropin was confirmed. Partial chemical analysis consisting of amino acid analysis and tryptic peptide mapping was carried out with the aid of sensitive fluorescence detection.

A unique type of radioimmunoassay is described that does not require centrifugation or separation. Microbeads containing a fluorophor are covalently linked to antibody. When an 125I-labeled antigen is added it binds to the beads and, by its proximity, the emitted short-range electrons of the 125I excite the fluorophor in the beads. The light emitted can be measured in a standard scintillation counter. Addition of unlabeled antigen from tissue extracts displaces the labeled ligand and diminishes the fluorescent signal. Application of scintillation proximity immunoassay to tissue enkephalins, serum thyroxin, and urinary morphine is described. Applications of the principle to study the kinetics of interaction between receptors and ligands are discussed.

New York City, with six medical schools and an elaborate emergency medical system, would appear to be a locale with optimal resources for coronary care. To assess coronary care facilities and practices, a comprehensive questionnaire was prepared by a multidisciplinary committee and submitted to 72 hospitals. Seventy-nine percent (57/72) responded, including all medical school affiliated hospitals and 41 of the 45 with more than 300 beds. Twenty-nine percent (16/55) did not have a coronary care unit separate from a general intensive care unit. Thirty-three percent (18/55) of coronary care units were designed before 1970. Although 85% (46/54) of the coronary care units had a 1:2 registered nurse per patient ratio during days, only 43% (23/54) maintained this ratio at night. Central monitoring was available in all hospitals, but only 40% (21/52) indicated 24-hour continuous monitor observation. Forty-five percent (25/55) had cardiac catheterization facilities, and 43% (24/56) had an intra-aortic balloon available. Forty-six percent (26/57) of coronary care units transferred post-myocardial infarction patients to non-monitored general beds. Fifty-eight percent (31/53) offered dietary counseling to patients, and 33% (18/54) had an inpatient cardiac rehabilitation program. Thus, New York City hospitals demonstrate a marked variability in coronary care unit facilities and practices and a substantial number of hospitals deviate from published recommendations for coronary care units.

In our first 80 attempts of percutaneous double balloon mitral valvuloplasty (BMV) 77 procedures have been successful. The mean patients age was 44 +/- 17 years, there were 16 men; 12 patients had previously been operated, 29 patients had important valvular deterioration (calcifications, thickening or unpliability) or of subvalvar system. For technical failure BMV was performed with only one balloon in 8 patients. BMV resulted in significant improvement in haemodynamic values: the mean capillary pressure fell from 22 +/- 6 to 12 +/- 5 mmHg (p less than 0.001), the mean mitral gradient from 15 +/- 6 to 5 +/- 3 mmHg (p less than 0.001). Cardiac index remained unchanged. The hemodynamic valve area, by Gorlin formula, increased from 1.09 +/- 0.29 to 2.19 +/- 0.72 cm2 (p less than 0.001). Doppler and echocardiography data were similar to haemodynamic data. Mitral valve area obtained with BMV was equivalent to the area usually obtained in closed mitral commissurotomy. There were 3 tamponades. The first, in a patient to whom BMV was not successful. For the 2 others, surgically evacuated, intracavitary pressures were measured after surgical pericardial drain. BMV was of little efficacy in one patient who died 3 days thoracotomy. The three tamponades were caused by straight tip balloon left ventricle perforation. There was no tamponade with pigtail tip catheter balloon. Mitral valve regurgitation was never increased more than 1 + Interatrial septal defect with QP/QS greater than or equal to 1.5 and less than 2 was present in 5 patients. BMV may be a useful alternative to surgery with low incidence of complication. Mitral valve area increase is similar with both treatment.

This case report describes an orthotic management option for the treatment of persistent subtalar and ankle joint pain in a patient with rheumatoid arthritis. Orthotic design, principles of control, and methods of application are discussed in addition to the advantages and disadvantages of prefabricated and custom-formed orthotic devices.

A sensitive and rapid radioreceptor assay has been developed to monitor opioid peptides in column effluents. It is based on competitive binding to NG 108-15 cells using [3H-Tyr]Leu-enkephalin as the displaced ligand. The specificity of binding to the cells of naturally occurring opioid peptides and synthetic analogs has been shown to be similar to that found with synaptic plasma membranes.

An immunological approach to the study of the structure and biogenesis of the phosphatidylinositol glycan (PI-G) membrane anchor at the carboxyl terminus of human placental alkaline phosphatase (PLAP) is described. Based on the protein sequence predicted from full length PLAP cDNA, two epitopes were chosen in the region of the carboxyl terminus for the production of site-directed antibodies. The exo site represents the last nine residues of preproPLAP, (res. 505-513), which is part of the sequence that is expected to be cleaved from the nascent protein during processing and addition of the PI-G tail. A second site, the endo sequence, was selected close to the expected carboxyl terminus in mature PI-G-tailed PLAP (res. 474-484 of proPLAP). The two peptides were synthesized, polyclonal antibodies to the conjugated peptides were prepared, and the antisera were characterized. Analytical methods for both synthetic peptides and proteins are presented. Preliminary applications to the isolation and characterization of the PI-G-linked carboxyl terminus of mature PLAP and to the characterization of nascent PLAP are described. The application of both carboxyl terminal-directed antibodies, and a third antibody directed to the amino terminus of mature PLAP, in studies employing mutant forms of PLAP and to the PI-G tailing process itself are discussed. The immunological approach used here for PLAP should be applicable generally to the study of other PI-G-tailed proteins.

We have studied the temporal relation between psoriasis and psoriatic arthritis in 27 patients receiving photochemotherapy for treatment of psoriasis. Patients were classified as either spondylitic or nonspondylitic. For spondylitic patients, psoriasis was difficult to control, arthritis did not improve, and skin and joint activity appeared to vary independently. In contrast, 67% of nonspondylitic patients receiving photochemotherapy treatment remained clear of psoriasis, with 49% mean improvement in articular index. There was an inverse relation between initial percentage of psoriasis and improvement in peripheral arthritis. These results suggest that aggressive management of psoriasis helps control synovitis in at least a subgroup of patients with psoriatic arthritis.

Liver changes and associated host responses were evaluated in four groups of male rats, weighing 300 +/- 20 gm., which received intravenous injection of 2.2 times 10(9) live Escherichia coli. This bolus was given either without additional treatment (group A) or prior to the following regimens: intramuscular injection of gentamicin sulfate, 5 mg. per kg. (group B); intravenous injection of methylprednisolone sodium succinate, 40 mg. per kg. (group C); and intramuscular injection of gentamicin immediately after methylprednisolone sodium succinate treatment (group D). Rats given injections of saline or methylprednisolone sodium succinate served as controls. Survival rates at 10 and 20 hours were 25 per cent and 4 per cent for group A; 44 per cent and 28 per cent for group B; 94 per cent and 70 per cent for group C; 98 per cent and 98 per cent for group D, respectively. In rats of groups A and B, killed at 1, 2, 4, and 6 hours, progressive liver changes included intravascular sequestration of rapidly degranulating leukocytes, fibrinous deposits, and platelet aggregates in sinusoids as well as in spaces of Disse adjacent to subendothelial collagen, and extensive Kupffer cell disruption in association with severe midzonal necrosis. These alterations were accompanied by progressive hypoglycemia and elevations of serum enzymes, glutamic pyruvic transaminase, lactate dehydrogenase, and glutamic oxaloacetic transaminase. Hematologic studies revealed that E. coli bacteremia results in rapid leukopenia and disseminated intravascular coagulation primarily due to activation of the intrinsic coagulation pathway. All above reactions were delayed and markedly reduced in rats treated with methylprednisolone sodium succinate. The results indicate that antibiotic treatment of lethal, Gram-negative bacteremia is effective only in conjunction with early steroid treatment. The protective effects of glucocorticoids on the liver microcirculation and polymorphonuclear leukocytes appear to play a basic role in preventing the early development of disseminated intravascular coagulation, hepatocellular necrosis, and associated major host responses, thereby attenuating lethality of gram-negative septic shock.

Frequent symptoms of back and neck stiffness led to a radiographic investigation of the vertebral spine in patients receiving synthetic retinoids, isotretinoin and etretinate. X-ray examination of fifty patients with various skin disorders who received retinoids for at least 2 years were compared with seventy-two age- and sex-matched untreated patients. Differences in frequencies of defined abnormalities, which included anterior spinal ligament calcification and presence of osteophyte at two or more vertebral levels in the absence of joint space narrowing, were determined for treated and untreated patients. When the entire group of treated patients was compared with the entire group of those untreated, no statistically significant differences were observed. When only patients with basal cell nevus syndrome ( BCNS ) or basal cell carcinoma (BCC) who had never received retinoid were compared with those who received isotretinoin, the frequency of the defined abnormalities was significantly higher in the treated group (P less than 0.01). This study suggests that the ingestion of isotretinoin at mean total dose of 150,060 mg for an average of 2.9 years is associated with a statistically significant increase in developing an associated ossifying diathesis in patients with BCNS or BCC, when compared with matched, untreated controls.

A case of left ventricular perforation by straight-tipped balloon catheter during double-balloon mitral valvuloplasty with fatal outcome is presented. Technical considerations to prevent this complication are discussed.

We performed human lymphocyte alloantigen determinations in patients with psoriatic arthritis (PsPA) who were clinically classified into arthritic subtypes and disease severity. The total PsPA group demonstrated elevations of HLA-BW38, CW6, DR4 when compared with controls (p less than 0.001). Severe arthritics have increased DR4 frequency when compared with less severe arthritics (p less than 0.02). Those with mild disease have increased A3, B7 frequency which was absent in patients with moderate or severe arthritis. Rheumatoid-like PsPA patients have increased DR4, B40 frequencies; those with spondylitis, B27, CW1. PsPA is associated with many genes in the major histocompatibility complex. Distinct groups of patients with PsPA as determined by type and severity are identifiable by the presence of specific human lymphocyte antigens.

The study reported here involved a systematic attempt to withdraw medication from participants in a community-based hypertension treatment program. Sixty-six of 88 patients with well-controlled mild or moderate disease had medication withdrawn after at least six months of treatment; nonpharmacologic intervention was not employed. After one year, 44 (66.6%) remained normotensive and drug free; after two years, 33 (50.0%). Of the 29 patients still available for three-year follow-up, 15 (51.7%) were still normotensive and drug free. Withdrawal of medication was associated with correction of hypokalemia and reversal of impaired glucose tolerance. Thus, nearly one fourth of these patients, who were believed to be reasonably representative of those with mild or moderate hypertension, could discontinue drug therapy and remain normotensive for at least one year. Substantial medical and economic benefits are to be realized from wide replication of this experience.

Alkaline phosphatase is anchored to the plasma membrane by a carboxyl-terminal phosphatidylinositol glycan moiety. To investigate the biosynthesis of mature alkaline phosphatase, nascent human placental alkaline phosphatase was expressed in a cell-free system and used as substrate for in vitro processing by microsomal extracts. By monitoring the processed product with three site-directed antibodies, it was shown that microsomal extracts from CHO cells that contain other recognized processing activities also remove the carboxyl-terminal signal peptide from the preproenzyme in an apparently selective manner. This peptidase-like cleavage may be brought about by the action of a specific transamidase acting on the nascent protein in the absence of an appropriate phosphatidylinositol glycan cosubstrate.

The octapeptide Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu was recently isolated from bovine adrenal chromaffin granules and serves as a marker for proenkephalin from which it is derived. Polyclonal antisera which are highly specific for the carboxyl terminus have been raised against the synthetic peptide. The only significant cross-reactivity was with the 18.2-k Da and 5.3-k Da enkephalin-containing peptides (EC peptides) which contain the octapeptide at their carboxyl termini and the [des-Tyr] and [des-Tyr-Gly] congeners of the octapeptide. Extracts of bovine adrenal medulla and rat spinal cord were shown to contain significant amounts of the octapeptide, the two larger EC peptides, and the two smaller congeners.

The symptomatic joint disease secondary to avascular necrosis of bone (ANB) in 31 of 375 (8 per cent) patients with systemic lupus erythematosus (SLE) was characterized by polyarticular (90 per cent) and symmetric (83 per cent) involvement. Progressive deterioration requiring orthopedic intervention occurred in 11 (35 per cent) patients. No distinguishing clinical or treatment differences were found comparing patients with symptomatic ANB and selected cortico-steroid-treated, asymptomatic, control subjects with SLE. Complete roentgenographic surveys revealed symmetric, polyarticular abnormalities of subchondral and cortical bone consistent with ANB in eight of 31 (26 per cent) of the control subjects. A positive correlation was found between roentgenographic ANB and disease treatment with high doses of corticosteroids. The study suggests that ANB may be present in excess of 30 per cent of the patients with SLE and is most often subclinical, asymptomatic and nonprogressive.

Placental alkaline phosphatase (PLAP) is anchored to the plasma membrane by a phosphatidylinositol-glycan (PI-G) moiety. During processing of nascent PLAP, a 29-residue COOH-terminal peptide is cleaved out and the PI-G moiety is attached to the newly created COOH terminus of the mature protein. To investigate the structural requirements of the COOH terminus of the nascent protein for PI-G tailing and anchoring to the plasma membrane, we have transfected COS cells with wild type and mutant forms of cDNA encoding human prepro-PLAP. Utilizing a series of COOH-terminal deletion mutants of prepro-PLAP, it was found that to be PI-G-tailed the newly synthesized protein must possess an uncharged, predominantly hydrophobic amino acid sequence of a minimal length in the COOH-terminal peptide. While forms of prepro-PLAP with 17 consecutive hydrophobic residues in the terminal sequence yielded PI-G-tailed and membrane-bound products, prepro-PLAP mutants with 13 or fewer of such residues yielded hydrophilic proteins that were no longer PI-G-tailed but efficiently secreted into the medium. Studies using cassette mutants demonstrated that the precise amino sequence of the COOH-terminal region could be altered as long as minimal hydrophobicity and length was maintained.

The complex of elongation factor Tu with GTP (EF-Tu.GTP) reacts with N or epsilon -bromoacetyl-lys-tRNA ( or epsilon BrAcLys-tRNA) to form a functional covalently linked complex (XLTC). The site of cross-linking must be near the site on EF-Tu.GTP that binds the aminoacyl moiety of aminoacyl transfer ribonucleic acid (AA-tRNA). For identification of this site, a nanomole of purified XLTC prepared from or epsilon BrAc[(14)C]Lys-tRNA was digested first with RNase A and then with trypsin, and the peptides were resolved by high-performance liquid chromatography using a c8 reverse-phase column. A single peptide contained 80% of the label. The amino acid composition of this peptide was identical with that of residues 59-74 in EF-Tu. The NH2-terminal sequence of the peptide was determined to be Fly-Ile-Thr-Ile, which are residues 59-62 in EF-Tu. The modified amino acid was identified as pi - (carboxymethyl)histidine, which establishes that His-66 is at or near the AA-tRNA binding site on EF-Tu.GTP.

An analysis of the mechanisms of action of balloon valvuloplasty in adult aortic stenosis (AS), based on postmortem studies on fresh specimens and on clinical experience with 300 consecutive cases, is reported. When maximally inflated, a 20-mm diameter balloon (occupying a 3.14 cm2 cross-sectional area) significantly enlarges the stenosed valve orifice by 3 mechanisms: stretching of valve tissue, rupturing of commissural fusion and breaking of calcific deposits. These last 2 mechanisms are the most effective, in both tricuspid and bicuspid forms of AS, to render the cusps more flexible and able to open during systole and to close at the time of ventricular diastole. The marked increase in valve area obtained by the dilatation procedure was clearly demonstrated on fresh postmortem specimens and also on postmortem examination of cases that had had balloon valvuloplasty during life. Stretching alone may give only a temporary increase in valve area with an elastic return of the leaflets to their initial stenosing position and may explain, at least in part, the occurrence of restenosis. Inflation of the balloon is well tolerated with no deleterious decrease in blood pressure in two-thirds of the cases because the balloon opens the commissures, allowing blood ejection through these openings. It does not produce calcific emboli, probably because calcium deposits remain imbedded in the leaflets, covered by the endothelium. Finally, it very infrequently produces acute severe aortic regurgitation. Careful choice of balloon size is necessary to obtain on effective opening; most often a 20-mm diameter balloon but sometimes a balloon up to 23 mm is used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP phosphodiesterase (PDE; EC 3.1.4.17) in Thermomonospora curvata was purified and characterized. Fractionation of cell extracts by ion-exchange and size-exclusion chromatography revealed four PDE isozymes, which differed markedly in molecular weight, theophylline sensitivity, pH optima, and substrate affinity. Although the enzyme was labile after purification, total recovery of PDE activity was fivefold that of the crude extract. PDE biosynthesis appeared sensitive to the growth phase, growth rate, and carbon source. PDE levels in batch cultures peaked and declined rapidly during mid-exponential-phase growth. In continuous culture, maximal PDE and cellulase production occurred at dilution rates yielding mean cell generation times of about 5 and 17 h, respectively. The addition of glucose to cellulose-grown cells caused declines in both cyclic AMP and PDE levels, suggesting that the enzyme was subject to, rather than the agent of, catabolite repression.

"How do you combine work and family life?" is a question that has much relevance for busy professionals and their families. For physicians especially the dilemma of combining both is particularly acute. As a group committed to caring for others, how do physicians decide that their own and their families' needs are also important, and how do they find the time and energy to tend to those needs? The author closely followed a group of practicing physicians and their families for more than five years in an effort to understand the above questions. During this process of listening, talking, and observing, issues of "specialness," "work," "time," and "caring" were repeatedly mentioned by those professionals and families he followed. He found that the way medical families dealt with these specific notions helped determine the outcome of their struggle with the career/family dilemma.

The role and timing of physical therapy following axillary dissection for melanoma, or in conjunction with modified radical mastectomy has not been extensively studied. A prospective randomized clinical trial was carried out over an 18-month period in the Surgery Branch, National Cancer Institute (NCI) and Department of Rehabilitation Medicine, Clinical Center, in which patients were assigned to receive one of two postoperative physical therapy regimens. Patients were assigned to receive graduated increases in allowed range of motion (ROM), either beginning on postoperative day 1 (early) or day 7 (delayed). All patients were advanced to full pain-free ROM when the suction catheters were removed. A total of 36 patients with 40 axillary dissections (19 for melanoma, 21 for breast cancer) were included in this study. Patients randomized to receive early motion had more total wound drainage (805 +/- 516 cc vs. 420 +/- 301 cc, p < 0.01), more days of drainage (10.3 +/- 5.3 vs. 6.2 +/- 2.7, p < 0.01), and later postoperative day of discharge (12.8 +/- 5.1 days vs. 9.2 +/- 4.0 days, p < 0.02) than did patients who started motion on day 7. Wound complications including infection and small areas of skin breakdown occurred more frequently in the early group (seven patients vs. one patient, p < 0.02). No significant differences in the per cent of patients achieving functional ROM could be identified between these two groups at one, three or six months after operation. Transient serratus anterior palsy (12 patients) and latissimus dorsi palsy (2 patients) occurred in approximately 30% of all patients, regardless of group (breast vs. melanoma, early vs. delayed), but returned to normal in all patients. The early institution of flexion and abduction exercises following axillary dissection thus appears to have a deleterious effect on wound healing and drainage. Adequate functional ROM is attained in all patients with a minimum of complications when active motion exercises are delayed for up to 7 days after axillary dissection.

Twenty-four above-knee amputees (AKA) treated with rigid plaster dressings were randomized to receive ambulation on pylon within 24 hours of surgery or at time of suture removal. Casts were applied by physical therapists in half of each group, and by a prosthesist in the other half. There were no statistically significant differences among the groups with respect to age, sex, stump length, gait characteristics and wound healing. Time to prescription of final prosthetis was similar in all groups. Specifically, there was no delay in the group ambulated immediately. The immediate ambulators did have significantly greater stump pain requiring more analgesia than the group ambulated after suture removal. Patients with case applied by physical therapists used their prostheses more than patients with cases applied by prosthetists. There was no detectable difference among treatment groups with regard to participation in therapy, acceptance of prosthesis, and psychological status. Recommendation for management of AKA's include: use of rigid dressing; ambulation on pylon after suture removal; utilization of physical therapist for application of rigid dressings and alignment of pylon.