Amoebic relaxant derived factor with activity on vascular smooth muscle.
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Biomedical subjects
Publications and source records attributed to M A Hernandez.
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Three immunohistochemically different myelomonocytic subtypes, i.e. MRP8, MRP14 and 27E10 were quantitatively evaluated in the intraalveolar, alveolar-interstitial and alveolar-intracapillary lung compartments. Lung sections from 5 major groups with defined causes of death, i.e. drowning and death during immersion (DI), cerebral/intracranial haemorrhages (CH), sudden cardiac deaths (SCD), hanging and throttling (HT) and immediate trauma deaths (ITD) were stained and the positive cells counted. The results show clear differences of the cell numbers on average. Among the different compartments the intracapillary cell count exhibits the highest numbers. If the cell counts are compared to the different causes of death, DI shows the highest values and ITD the lowest. The individual values, however, show considerable variations in all compartments and especially in the low cell count range. Within the DI group two subgroups can be differentiated, one having low and the other one having high cell numbers. This can be due to the type of agony, i.e. drowning versus immersion/hydrocution, or to resuscitation attempts or to a combination of both factors.
BACKGROUND: The Breast Cancer Screening Module is a professional training course within the Professional Education for Prevention and Early Detection (PEPED) program at the University of Texas M. D. Anderson Cancer Center. An outcomes study was done to determine the module's ability to improve screening practices crucial to breast-cancer control. METHODS: The five-day course combines 17 hours of class work with 20 hours of hands-on clinical training. Subjects were followed for one year post-training. Six outcome areas were evaluated: 1) knowledge about breast-cancer prevention; 2) clinical skills; 3) changes in routine practice; 4) numbers of patients screened, referred, and diagnosed; 5) trainee satisfaction with the course; and 6) barriers to implementing screening in routine practice. The study population was 63 subjects (all nurse professionals). RESULTS: Outcomes were positive in all six evaluation areas-significant gains in general and clinical knowledge tests (p < or = 0.05); a significant increase from 54.2% pre-training to 70.5% post-training in risk counseling (p < or = 0.05); a sustained increase in screening practices (4.3 times and 2.8 times greater at 6 and 12 months post-training, respectively); 72% rate of high course satisfaction; and barriers to improved screening practices, such as time limitations among 60.4% of subjects and 57.6% of their employers, were identified. CONCLUSIONS: This unique training enhances breast-cancer prevention and screening practices and early detection.
Amino acid and peptide thioesters which contained Arg or Lys in the P1 position were tested as substrates for rat skin tryptase, and the kinetic constants Kcat/KM for the better substrates such as Z-Aba-Arg-SBzl, and Z-Gly-Arg-SBzl were over 5,000,000 M-1 s-1. The inhibitory potency of arginine fluoroalkyl ketones, benzamidine derivatives, and substituted isocoumarins containing basic functional groups was studied with rat skin tryptase, human lung tryptase, human skin tryptase, and bovine trypsin. 1-Naphthoyl-Arg-CF3 was the best arginine fluoroalkyl ketone reversible inhibitor for rat skin tryptase with a KI of 0.9 microM. 1-(4-Amidino-phenyl)-3-(4-phenoxyphenyl) urea showed competitive inhibition against bovine trypsin and rat skin tryptase with KI values of 2 and 4 microM, respectively. Isocoumarin derivatives with isothioureidoalkoxy substituents at the 3 position were potent irreversible inhibitors of these three tryptases with Kobs/[I] values of 10(4)-10(5) M-1 s-1. 4-Chloro-3-(2-isothioureido)ethoxy-7-phenylcarbamoylaminoisocou marin and 7-benzylcarbamoylamino-4-chloro-3-(3-isothioureido)propox yisocoumarin inactivated trypsin and formed stable trypsin-inhibitor complexes which regained less than 8% of activity upon standing in the pH 7.5 buffer and regained 30-75% of activity in the presence of 0.3 M NH2OH after 1 day. In contrast, the complexes with rat skin tryptase regained activity rapidly, indicating differences in the inhibition mechanism and active site structures of these related enzymes.
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A series of new acyl, urea, and carbonate derivatives of 7-amino-4-chloro-3-methoxyisocoumarin were synthesized and evaluated as irreversible inhibitors of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE). Inhibition of HNE is directly related to the hydrophobicity of the substituent on the 7-amino group. The N-Tos-Phe derivative (19) is the best HNE inhibitor with a second-order rate constant kobs/[I] = 200,000 M-1 s-1. The closest analogue in this series, the 3,3-diphenylpropionyl derivative 5, had a kobs/[I] = 130,000 M-1 s-1 with HNE. In contrast to the Tos-Phe derivative 19, phenylacetyl derivative 2 and carbonates 22 and 25 gave extremely stable enzyme-inhibitor complexes with deacylation half-lives longer than 48 h with both elastases. N-Phenylurea derivative 25 was the best inhibitor for PPE with a second-order rate constant kobs/[I] = 7300 M-1 s-1. The crystal structure of a complex of PPE with N-tosyl-Phe derivative 19 was determined at 1.85-A resolution and refined to a final R factor of 16.9%. The isocoumarin forms an acyl enzyme with Ser-195, while His-57 is near the inhibitor, but not covalently linked. The Tos-Phe makes a few hydrophobic contacts with the S' subsites of PPE, but appears to be interacting primarily with itself in the PPE structure. This region of HNE is more hydrophobic and modeling indicates that the inhibitor would probably make additional contacts with the enzyme.
From 1987 to 1989, 42 patients with locally advanced squamous cell carcinoma of the head and neck (Stages III-IV, Mo) were randomized to receive radiotherapy (Group A) or three courses of induction chemotherapy followed by radiotherapy (Group B). There were 36 evaluable patients, 17 in Group A and 19 in Group B. The radiotherapy regimen was the same for both groups, 66-74 Gy total tumor doses with standard fractionation scheme of 2 Gy/day. The chemotherapy regimen was a combination of carboplatin 400 mg/m2 by intravenous bolus injection on day 1, and Ftorafur 1,000 mg/m2 orally once a day for 14 days. Cycles were given every 4 weeks. The complete response rate in Group A was 65%; in group B it was 31.5% after induction chemotherapy and 84% after radiotherapy. The 42-month actuarial overall survival rates were 34% for Group A and 47% for Group B (P = NS). Patients from both groups with a complete response had a significantly longer survival time than those with a partial response (P less than 0.001). No significant differences in disease-free survival were found between the two treated groups. The chemotherapy regimen was well tolerated, with moderate hematologic and gastrointestinal toxicity. Increased in radiation toxicity by chemotherapy was not observed.
To evaluate the analgesic and antiinflammatory properties of oral streptokinase-streptodornase (SS) in cases of minor trauma, 190 patients with ankle sprains were studied. Subjects were randomly given an active drug or a placebo in doses of two tablets three times a day for eight days. A scoring system was used to rate the following symptoms: spontaneous pain, mobilization pain, wearing pain, articular disability, flaccidity, muscular spasm, edema, and hematoma. Each symptom was categorized as none (0), mild (1), moderate (3), or severe (4). Patients were evaluated at the beginning of the study and on the fourth and eighth days of treatment. At the end of the trial, the decrease in each symptom score was significantly greater in patients receiving SS than in patients receiving a placebo. Analgesic intake during the study was also noticeably lower in the SS group. The incidence of drug-induced side effects (mainly abdominal discomfort) was minimal. Oral SS ameliorates the inflammatory symptoms associated with ankle sprains and therefore may be used as an alternative to nonsteroidal antiinflammatory drugs.
Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for procine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.
C-reactive protein were assayed both with immunodiffusion and precipitation on latex C-reactive protein in 216 samples of sera from newborns with suspected septicemia. Both methods correlated well (r = 0.92) rendering the second one rather useful for early diagnosis of neonatal sepsis, since it produces results within a few minutes independent of complicated apparatus or trained personal.
Serial measurements of 11 serum proteins have been made throughout 39 admissions of 36 patients to hospital for the treatment of acute attacks of ulcerative colitis. There was a striking correlation between rapid changes in C-reactive protein and pre-albumin concentrations and the clinical response to medical treatment. Measurements of the alpha1-acid glycoprotein, albumin, and total serum protein concentrations at the time of admission were found to correlate with the outcome of the attack. Measurement of these proteins provides a useful guide to the management of patients with attacks of ulcerative colitis.
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27 children, aged 7 months to 15 years, with terminal renal failure and no available vascular access, were treated with chronic peritoneal dialysis for 3 weeks to 9 months (mean 3 months). An indwelling silicon catheter fitted with a subcutaneous dacron felt cuff was used; the average catheter life time was 10 weeks (3 to 25 weeks). Control of uremia was satisfactory with mean serum urea decreasing from 2 to 1 g/l and creatinine from 130 mg/l to 60 mg/l after 48 hours of dialysis. No uremic complications occured. Total serum protein remained stable: mean: 62 g/l prior to treatment and 60 g/l after the treatment period. Hematocrit was higher than in hemodialysed children (17% versus 15%). Three children were directly transplanted without difficulty. However, some complications did occur. There were 27 episodes of catheter obstruction leading to 12 surgical interventions. 18 episodes of peritonitis (5% of total dialyses) occured in 12 patients, and two were lethal. The frequency of complications prohibits a recommendation of chronic peritoneal dialysis over hemodialysis in children; this technique however remains very helpful in those situations where vascular access is difficult.
Between 1970 and 1992, 23 patients with cubitus varus deformities following elbow fractures underwent 26 corrective lateral-wedge osteotomies at Texas Scottish Rite Hospital. Internal fixation was most commonly provided by either small Steinmann pins, two screws and a figure-of-eight wire, or a small two-hole plate. Sixteen patients had a good result and 10 were judged to have poor results. Two of the 10 patients with poor results had inadequate intraoperative correction. Unstable internal fixation allowed osteotomy fragments to slip into varus in the remaining eight poor results (three with Steinmann pins and five with figure-of-eight wire). Nonrigid internal fixation was obvious even in the patients who received good correction of their cubitus varus. Of the 16 patients with good postoperative results, six demonstrated loss of fixation with extension of the distal fragment. In addition, seven patients with poor results also had slippage of the distal osteotomy fragment into extension. These patients had between 5 and 15 degrees of apparent elbow hyperextension with concomitant loss of elbow fixation. We now recommend a two-hole lateral plate and a percutaneous medial pin to enhance the stability of internal fixation.
The authors assert that some of the most regressed, treatment-resistant clients with persistent mental illness will show a favorable response to a group approach called remotivation therapy. The remotivation therapy techniques of the 1950s have been updated by psychiatric nurses and a social work clinician in one VA setting. The authors assert that remotivation therapy approaches are easy to implement, personally rewarding, and effective in promoting interaction in such clients.