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Biomedical subjects

C McCabe

Publications and source records attributed to C McCabe.

At least 55 records · Page 3Linked to original sources

Clinicopathological findings in human autopsy eyes with an Anis circular lens.

PURPOSE: To evaluate the long-term performance of the Anis circular intraocular lens (IOL). SETTING: Center for IOL Research, Storm Eye Institute, Charleston, South Carolina. MATERIALS: Fifteen human autopsy eyes with an Anis circular IOL submitted between 1985 and 1993 were evaluated. The eyes were sectioned at the equatorial plane, and the anterior segment containing the capsular bag and the IOL was photographed from the posterior perspective. Fixation, centration, capsular bag shape, zonular damage, central posterior capsule opacification (PCO), and Soemmering's ring formation were analyzed. The results were compared with those of a control group comprising human autopsy eyes with a one-piece (n = 15) or three-piece (n = 15) poly(methyl methacrylate) IOL with a C-loop design. RESULTS: All 15 Anis IOLs showed symmetrical in-the-bag fixation. Mean decentration in the Anis IOL eyes was significantly lower than in the control eyes (P = .02). Eyes with the Anis IOL had fewer zonular defects (P = .0005) and a better circular extension of the capsular bag (P = .003). There were no statistically significant differences in PCO (P = .29) or Soemmering's ring formation (P = .67). CONCLUSION: The Anis IOL with a circular haptic design had better centration and capsular bag morphology than the control eyes, although a difference in PCO and Soemmering's ring formation could not be shown.

Aged↗

Plantar foot pressures during treadmill walking with high-heel and low-heel shoes.

The effect of walking with high-heel shoes on plantar foot pressure distribution was investigated. Ten normal women walking in shoes with low heels were compared to women walking in high-heel shoes. It was shown that high-heel shoes increased the load on the forefoot and relieved it on the hindfoot. The load passed toward the medial forefoot and the hallux. The lateral side of the forefoot showed a decrease in contact area, reduced forces, and peak pressures. The medial side of the forefoot had a higher force-time and pressure-time integral. It is suggested that these higher loads on the medial forefoot may aggravate symptoms in patients with hallux valgus deformity.

Adult↗

Use of anti-CD3 epsilon F(ab')2 fragments in vivo to modulate graft-versus-host disease without loss of graft-versus-leukemia reactivity after MHC-matched bone marrow transplantation.

The use of T cell-specific mAb in vivo for prevention and treatment of graft-vs-host disease (GVHD) and its impact on graft-vs-leukemia (GVL) reactivity was examined in a murine model of MHC-matched bone marrow transplantation (BMT). F(ab')2 fragments of a CD3 epsilon-specific mAb were administered to irradiated AKR (H-2k) hosts after transplantation of BM plus spleen cells from B10.BR donors (BMS chimeras). The effects on GVH and GVL reactivity were Ab dose- and schedule-dependent. A short course of mAb (qe2d, days 0 to 8) prevented clinical evidence of GVHD and mortality. Anti-CD3 F(ab')2 mAb reversed clinical symptoms of acute GVHD when delayed up to 18 days post-transplant. Anti-host (Mls-1a)-specific V beta 6+ cells were absent from the spleens of GVH-negative control mice, but persisted in Ab-treated BMS chimeras despite the absence of GVHD. Leukemic mice given 16.7 micrograms of Ab on days 0, 2, and 4 survived leukemia-free without developing severe GVHD. A longer course of Ab completely prevented GVHD, but led to leukemia relapse in tumor-bearing hosts, despite engraftment of donor T cells. The GVL effect was quantitatively stronger when Ab was used for GVH therapy as compared with GVH prevention. Some Ab-treated, GVH-free chimeras relapsed with lymphomas in unusual sites, suggesting that occult tumor cells may persist in nonlymphoid tissues. These experiments demonstrate that T cell-specific mAb can be used successfully in vivo to avoid severe GVHD, but that excessive or ill-timed administration of Ab may eliminate GVL reactivity.

Animals↗

Analysis of 100 explanted one-piece and three-piece silicone intraocular lenses.

PURPOSE: The authors analyzed incidence and types of complications seen after implantation of silicone posterior chamber intraocular lenses (PC IOLs). These data were compared with those obtained in previous studies with standard polymethylmethacrylate IOLs. METHODS: Data from the laboratory database were collected on 100 explanted silicone IOLs submitted to the Center for Intraocular Lens Research from 1986 to 1994. RESULTS: Of the 100 IOLs, 63 were three-piece designs with polypropylene loops and 37 were one-piece plate lenses. The two most important reasons for explantation were IOL decentration (42.0%) and inflammation (27.7%). There was no significant difference for the reasons of explantations between one- and three piece IOLs (P > 0.1). Intraocular lenses that had been removed due to inflammatory reactions had a significantly longer implant duration (19.2 +/- 18.9 months) than lenses that were explanted because of decentration (9.19 +/- 12.1 months) (P = 0.018). CONCLUSIONS: The results presented here showed that there is no substantial difference between these IOLs and polymethylmethacrylate lenses in terms of reasons for explantation. The authors' data suggest that clinical outcome is not as dependent on the type of lens selected as it is on the quality of surgery. The key to good results is the use of "capsular surgery," namely techniques that ensure secure in-the-bag IOL fixation.

Cataract Extraction↗

Effect of the shoe on plantar foot pressures.

The bare foot plantar pressures were compared to in-shoe pressure measurements in 11 normal male volunteers using the EMED system. Shoes diminished pressures and forces in most areas under the foot except the medial forefoot. The hallux showed less force, a smaller contact area and a reduced contact time. Therefore a shoe can interfere with the toe-off mechanism. There was no difference between various types of shoes with rubber and leather soles. Heavier subjects tended to put less weight on the medial forefoot.

Adult↗

Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA Trial).

Previous studies have reported that some patients presenting with unstable angina are found at coronary angiography to have no critical coronary stenosis. This study evaluated the clinical presentation and arteriographic findings in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI-IIIA) trial, which assessed the effect of tissue-type plasminogen activator added to conventional therapy on the coronary arteriographic findings in patients presenting with ischemic pain at rest. Three hundred ninety-one patients were enrolled in the TIMI-IIIA trial and underwent coronary arteriography within 12 hours of enrollment. Fifty-three patients (14%) had no luminal diameter stenosis of a major coronary artery of > or = 60% on the baseline arteriogram. Compared with patients with unstable angina with an identifiable culprit lesion, patients without critical coronary obstruction were more likely to be women and non-white and less likely to have ST-segment deviation on the presenting electrocardiogram. Arteriography in such patients revealed no visually detectable coronary stenosis in half of the group; the remaining patients had noncritical coronary narrowing (i.e., < 60% luminal diameter stenosis) without morphologic features (ulceration or thrombus) suggestive of unstable or active coronary plaque. Nearly one third of the patients without critical coronary stenosis had impaired angiographic filling, suggesting a possible pathophysiologic role for coronary microvascular dysfunction. These patients with unstable angina and no critical coronary obstruction had an excellent short-term prognosis; 2% died or had myocardial infarction compared with 18% of patients with critical obstruction.

Angina, Unstable↗

Use of a standardized heparin nomogram to achieve therapeutic anticoagulation after thrombolytic therapy in myocardial infarction. TIMI 4 investigators. Thrombolysis in Myocardial Infarction.

BACKGROUND: The recently completed Thrombolysis in Myocardial Infarction (TIMI) 4 Study compared three thrombolytic treatment regimens for acute myocardial infarction. The treatment arms included front-loaded recombinant tissue plasminogen activator (rtPA), anistreplase (APSAC), or both, in conjunction with an intravenous bolus of 5000 U of heparin, followed by 1000 U/h. To facilitate anticoagulation, a heparin nomogram was developed to maintain the therapeutic activated partial thromboplastin time at 1 1/2 to 2 times the control value. METHODS: A poll revealed that nine centers made use of the recommended heparin nomogram and six did not, adjusting the heparin dosage according to local practice. Anticoagulation parameters, major hemorrhagic events, and the frequency of heparin interruption were compared between centers that used and did not use the nomogram. RESULTS: Subtherapeutic activated partial thromboplastin time values were noted in 4%, 14%, 29%, 46%, 37%, and 34% of patients 8, 12, 24, 48, 72, and 96 hours, respectively, after heparin treatment was begun. Patients with subtherapeutic values at 24 hours were younger (mean +/- SD, 55.2 +/- 10.6 vs 59.6 +/- 10.6 years, P = .02) and weighed more (86.4 +/- 13.5 vs 78.9 +/- 15.7 kg, P = .007) than patients with therapeutic values. Centers that used the nomogram had significantly fewer subtherapeutic values at 48 and 96 hours. In addition, heparin therapy was interrupted less frequently at centers that used the nomogram (38.1% vs 68.7%, P < .001). Major spontaneous hemorrhage, reinfarction, and reocclusion rates were low and were about the same in the two groups. CONCLUSIONS: The use of a heparin nomogram provided improved anticoagulation in patients treated with thrombolytic therapy for myocardial infarction. Weight- and age-adjusted heparin dosing may provide further improvement in anticoagulation with heparin therapy. Our findings support the need for frequent monitoring of the activated partial thromboplastin time and for a standardized approach to adjusting the heparin dosage.

Aged↗

Forefoot arthroplasty and changes in plantar foot pressures.

The aim of this study was to determine how effective forefoot arthroplasty is at reducing the pressures under the forefoot. The EMED F pressure measuring system was used. Fifteen patients (23 feet) were included in the study. All patients had foot pressure studies performed before and after surgery. Our results show a significant increase in total pressure and pressure-time integral under the foot after surgery. This increase was most marked under the first metatarsal head region (P < .005). However, the midmetatarsal region showed a slight decrease in pressure, but this was not significant. Symptomatically, 13 patients felt improved by the operation. The results suggest that the procedure is successful because it transfers the pressure to areas better able to tolerate it, rather than reduces the total pressure.

Adult↗

Characterization of a nerve growth factor-stimulated protein kinase in PC12 cells which phosphorylates microtubule-associated protein 2 and pp250.

Treatment of PC12 cells with nerve growth factor (NGF) resulted in the rapid, but transient, activation of a protein kinase which specifically phosphorylated an endogenous 250-kDa cytoskeletal protein (pp250). We report that the microtubule-associated protein, MAP2, is an alternative substrate for the NGF-activated kinase. NGF treatment maximally activated the kinase within 5 min; however, the activity declined with longer exposure to NGF. The enzyme was localized predominantly in microsomal and soluble fractions and phosphorylated MAP2 on serine and threonine residues. The soluble enzyme was fractionated by DEAE chromatography and gel filtration and had an apparent Mr of 45,000. The enzyme was purified to near homogeneity by chromatofocussing and had a pI of 4.9. Kinetic analysis revealed that NGF treatment caused a sevenfold increase in Vmax for MAP2. The Km with respect to the MAP2 substrate was approximately 50 nM and was not altered by NGF treatment. A novel feature of the NGF-stimulated enzyme was its sharp dependence on Mn2+ concentration. The active enzyme is likely to be phosphorylated, because inclusion of phosphatase inhibitors was required for recovery of optimal activity and the activity was lost on treatment of the enzyme with alkaline phosphatase. Histones, tubulin, casein, bovine serum albumin, and the ribosomal subunit protein S-6 were not phosphorylated by this enzyme. The NGF-stimulated kinase was distinct from A kinase, C kinase, or other NGF-stimulated kinases. The rapid and transient activation of the protein kinase upon NGF treatment suggests that the enzyme may play a role in signal transduction in PC12 cells.

Adrenal Gland Neoplasms↗

Immunoglobulin epitopes defined by synthetic peptides corresponding to joining region sequence: conservation of determinants and dependence upon the presence of an arginyl or lysyl residue for cross-reaction between light chains and T-cell receptor chains.

Joining or J region sequences of rearranging immunoglobulins and T-cell receptors show considerable sequence homology, particularly in their C-terminal portion corresponding to the fourth framework region of immunoglobulin variable regions. In order to test the question of whether serological cross-reactions between immunoglobulin variable regions and T-cell receptors were due to antigenic similarities in their J regions, we synthesized synthetic peptides corresponding to immunoglobulin J regions and to J regions predicted from gene sequence of the T-cell receptor beta chain. We found that antibodies produced against a synthetic 16-mer J beta sequence reacted with T-cell receptor chains and also with immunoglobulin light chains. The cross-reactivity was dependent upon the J signature sequence FG()GT(R or K)L where the presence of a positively charged lysyl or arginyl residue was essential for cross-reactivity. We were able to classify J region determinants into two distinct antigenic sets; one corresponding to JH and the other corresponding to J kappa, J lambda, J beta and J alpha. Although considerable homology occurs between JH and JL (or J beta) sequences, little cross-reactivity was observed between these two J subsets. Antibodies raised against polyclonal murine IgG immunoglobulins contained antibody subpopulations specifically reactive with either JH or J beta peptides. The serological data derived here using antipeptide antibodies are consistent with computer modeling studies that indicate that the conformations of T-cell receptor variable regions resemble those of classical immunoglobulins. Our data comparing cross-reactivities restricted to the J region indicate that the expression of the J region by intact T-cell receptor beta chains is probably more similar to that of light chains than it is to the corresponding region of heavy chains.

Animals↗

Embolism of the popliteal artery.

The experience with popliteal arterial embolism at the Massachusetts General Hospital was surveyed, and the results of therapy prior and after the introduction of the balloon-tipped embolectomy catheter were compared. During the 17 year period from January of 1964 to January 1981, 67 popliteal emboli were diagnosed. Nonsurgical management was successful in salvaging 11 of 13 extremities in ten patients with one death. Surgical embolectomy was performed upon 54 extremities in 48 patients with 40 limbs salvaged and 11 deaths. Although the percentage of patients undergoing surgical therapy for popliteal emboli has dramatically increased since the introduction of embolectomy catheters, no improvement in limb salvage or in patient survival has resulted. In fact, the limb salvage rate has declined. Nonsurgical management in appropriately chosen patients is clearly successful. The results of this survey emphasize the necessity of early diagnosis and treatment as well as selective patient management. Recommendations for a therapeutic approach to popliteal emboli are presented which hopefully will improve the results.

Aged↗

Current PTFE grafts: a biomechanical, scanning electron, and light microscopic evaluation.

Two currently available brands of PTFE grafts (Goretex and Impra) were studied in a canine femoral artery model to determine whether changes in the manufacturing processes of the two grafts, which increased their strength, had altered the biophysical properties and the histological reactivity of either graft. Both grafts were found to be similar except for differences in their suturability. Their in vivo dynamic compliances were almost identical (1.2 +/- 0.35 vs. 1.2 +/- 0.45). (Scanning electron microscopy showed endothelialization of the grafts only adjacent to the anastomoses, and light microscopy demonstrated similar degrees of histologic incorporation by the host tissues, though of slower tempo than that previously described. These results are examined and discussed with regard to the suitability of this model for characterizing new arterial prostheses of small to medium diameter.

Animals↗

Diagnostic quantification of CASS (coronary artery surgery study) clinical and exercise test results in determining presence and extent of coronary artery disease. A multivariate approach.

Multivariate linear discriminant function analysis on maximal exercise treadmill and angiographic data from 500 men with definite angina, 584 men with probable angina and 267 men with nonspecific chest pain identified independent predictors of presence and extent of coronary disease. We used the discriminant function to develop a clinical risk index and a clinical and exercise risk index for each patient subset. Probability curves were generated to predict the presence and extent of coronary disease. In definite angina cases, exercise testing provided more diagnostic information than clinical data alone. However, in the 10% of cases with the smallest risk indexes, half of the patients had coronary disease and one-quarter had multivessel disease. In men with probable angina, exercise testing added substantially more diagnostic information than clinical data. The probability of multivessel disease was reduced to less than 10% for 30% of patients with probable angina, an important diagnostic contribution. Exercise testing in men with nonspecific chest pain was of limited value because disease prevalence was already low.

Angina Pectoris↗