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Biomedical subjects

M Hoffman

Publications and source records attributed to M Hoffman.

At least 271 records · Page 15Linked to original sources

[Recurrent episodes of Morgagni-Adams-Stokes syndrome due to degeneration of atrio-ventricular tachycardias into atrial fibrillation in a patient with Wolf-Parkinson-White syndrome].

We present clinical problems and the therapy of a 52 year old patient with Wolf-Parkinson-White syndrome and numerous episodes of Morgagni-Adams-Stokes syndrome. In that patient atrio-ventricular tachycardia caused atrial fibrillation. Short refractory period of the accessory pathway and the ventricular muscle allowed for extremely fast ventricular rate with haemodynamic collapse and syncope. Long-term treatment with propafenone or amiodarone did not prevent the arrhythmias. Electrophysiological study pre- and intraoperation including the epicardial mapping were performed several weeks after discontinuation of therapy with amiodarone. The studies revealed left free wall accessory pathway. Dr. A. Biederman and al. performed dissection of the accessory pathway. There were no evidence of conduction through the accessory pathway during the post operation electrophysiologic study. The patient has neither reentrant tachycardias nor atrial fibrillation episodes.

Adams-Stokes Syndrome↗

Estradiol and progesterone receptors in human cutaneous melanoma.

The presence of estradiol and progesterone receptors (ER and PR, respectively) was assessed in 24 removed cutaneous melanomas, adapting the routine procedure used for the detection of the presence of these steroid hormone receptors in breast cancers. The study included only those cases which were not subjected to any anticancer therapy before surgery. The ER and PR values were comparable to those found in breast cancer and the tumors thus investigated could be classified in the same four distinct groups, namely ER+PR+, ER+PR-, ER-PR+, and ER-PR-. Each group is expected to exhibit a specific rate of response to endocrine therapy. No relation was found between the presence of steroid receptors and the type of tumor tissues (benign and primary tumors, recurrences or metastases), or the sex of the patients. Because of the small number of cases in each age group we could not correlate the levels of ER+ and PR+ with the age of the patients. Saturation analysis, competition studies and Scatchard analysis were performed in order to determine the characteristics of ER. Our data suggest that cutaneous melanoma cytosols contain a saturable, high affinity and low capacity, specific binding component for estradiol. Further investigations are required to show that estrogen responsive tissues are functional in either melanocytes or melanomas from any species.

Adolescent↗

Production of chemotactic peptides by neutrophil degradation of heparin cofactor II.

This study investigated the reaction of heparin cofactor II (HCII) with stimulated polymorphonuclear leukocytes (PMN). We have expanded upon previous studies showing that HCII can be degraded by stimulated PMN (Sie, P., Dupouy, D., Dol, F., and Boneu, B., Thromb. Res. 47, 657-664, 1987), and that chemotactic activity is produced when HCII is partially proteolyzed with purified leukocyte elastase or cathepsin G (Hoffman, M., Pratt, C.W., Brown, R.L., and Church, F.C., Blood, 73, 1682-1695, 1989). We found that HCII was proteolyzed by stimulated PMN, generating peptides with chemotactic activity. Both proteolysis and generation of chemotactic activity were inhibited by a specific leukocyte elastase inhibitor and by more general proteinase inhibitors. Leukocyte elastase activity was lost upon addition of either inhibitor. Heparin and dermatan sulfate altered the pattern of proteolysis. Our results suggest that HCII may be involved not only in functions related to thrombin inhibition but also in regulating acute inflammation.

Chemotaxis↗

A randomized clinical trial of prophylactic OKT3 monoclonal antibody in liver allograft recipients.

Seventy-nine hepatic allograft recipients were randomized to receive either conventional immunosuppression, including cyclosporine, azathioprine, and steroids (41 patients), or investigational therapy in which OKT3 replaced cyclosporine during the first postoperative week (38 patients). Early rejection occurred in 29 patients (71%) in the conventional group and 15 patients (39%) in the OKT3 group. Posttransplantation renal dysfunction occurred in 12 patients (29%) in the conventional group and 6 patients (16%) in the OKT3 group. Mean initial hospital stay was 34.1 +/- 18.8 days in the conventional group compared with 29.1 +/- 16.8 days in the OKT3 group. Cumulative patient survival (mean follow-up, 17.8 +/- 7.1 months) was 73.2% (30/41) for the conventional group and 84.2% (32/38) for the OKT3 group. Prophylactic OKT3 is indicated especially for liver allograft recipients with other complicating conditions that make management of early rejection unusually difficult.

Adult↗

PDGF-stimulated fibroblast proliferation is enhanced synergistically by receptor-recognized alpha 2-macroglobulin.

alpha-Macroglobulins derived from plasma or secreted by macrophages are platelet-derived growth factor (PDGF) binding proteins that compete with cell-surface receptors on fibroblasts for PDGF binding. alpha 2-Macroglobulin (alpha 2M) derived from bovine plasma was tested for its ability to modulate the PDGF-induced proliferation of primary passage rat lung fibroblasts (RLFs) and a human skin fibroblast cell line (CRL 1508). Fibroblasts were grown in 10% fetal bovine serum (FBS) for 24 hr, then washed with serum-free medium before adding serum-free defined medium (SFDM) containing insulin and transferrin. To this medium were added varying concentrations of human plasma-derived AB-PDGF and alpha 2 M, alone or in combination. Receptor-recognized alpha 2M was prepared by treatment with methylamine. Both native alpha 2M and the alpha 2M-methylamine (alpha 2M-MA) were tested for growth promoting activity in the absence or presence of PDGF. After 3 days, a concentration-dependent growth curve of fibroblast proliferation was demonstrated for PDGF alone, with near maximal stimulation reached at 15-20 ng/ml PDGF. alpha 2M and alpha 2M-MA alone had no effect on cell proliferation. However, alpha 2M-MA concentrations above 32 micrograms/ml synergistically enhanced PDGF-stimulated proliferation greater than 100% in the presence of 15 ng/ml PDGF. Native alpha 2M enhanced PDGF-stimulated growth 80-100% above PDGF controls only at low concentrations (32-64 micrograms/ml alpha 2M). High concentrations of native alpha 2M (128-256 micrograms/ml) either had no effect on growth or were inhibitory to PDGF-stimulated growth, depending on the cell type tested. Rat lung fibroblasts were shown to secrete a factor(s) that inhibited the trypsin-binding capacity of native alpha 2M. We further demonstrated that early passage RLFs possess specific cell-surface receptors for [125I]-PDGF and [125I]-alpha 2M-MA, and preincubation of RLFs with alpha 2M-MA increased the specific binding of [125I]-PDGF to the cell surface of these fibroblasts. Considered together, these data support the view that receptor-recognized alpha 2M synergistically enhances the proliferative capacity of PDGF. We postulate that receptor-recognized alpha Ms enhance PDGF-stimulated growth by increasing the local concentration of PDGF at the cell surface, where the PDGF could be released in close proximity to its own receptors.

Animals↗

Characteristics of the chemotactic activity of heparin cofactor II proteolysis products.

The physiological function of the serpin (serine proteinase inhibitor) heparin cofactor II (HCII) is not well understood. A role for HCII as an inhibitor of thrombin in the presence of dermatan sulfate and heparin has been proposed. Neutrophils (PMN) are the major cellular component of acute inflammation. HCII can be proteolytically inactivated by cathepsin G (CG) and elastase (LE), which are released by stimulated PMN. We have recently shown that reaction products of HCII with CG and LE are potent chemotaxins for PMN. Monocytes (monos) appear later in the course of inflammation than do PMN. They differentiate into macrophages in the tissues and participate in healing of damaged tissue and initiating immune responses. We found that the proteolysis products of HCII were chemotactic for monocytes in a fashion similar to their effects on PMN. At 10(-8) to 10(-9) M, the chemotactic activity of HCII proteolysis products was comparable to that of 10(-8) M N-formyl-Met-Leu-Phe (fMLP). The chemotactic activity of HCII-proteinase reaction products is mediated by a different mechanism than that of alpha 1 proteinase inhibitor (alpha 1 PI)-LE complexes or fMLP. Our data suggest that chemotactic activity generated by proteolysis of HCII is not due to the conformational change induced by cleavage of the exposed loop near the reactive site nor by release of the reactive site peptide. We also compared the effects of HCII reaction products and fMLP on expression of Mac-1 and p150,95 adhesive proteins. Mac-1 has been implicated in mono adhesion and chemotaxis and as a potential initiator of coagulation. The surface expression of Mac-1 was not increased above control levels by incubation of leukocytes with HCII digests, even though fMLP did increase surface Mac-1. Proteolysis products of HCII could play a role in the initial influx of PMN into a thrombus, and in the transition from acute to chronic inflammation, or to granulation and healing.

Antigens, Differentiation↗

Interstitial radiotherapy for the treatment of advanced or recurrent vulvar and distal vaginal malignancy.

From March 1, 1985 to April 30, 1988 10 patients with locally advanced primary or recurrent vulvar or distal vaginal malignancy were managed with interstitial radiotherapy with or without teletherapy. One patient died of complications of a total pelvic exenteration for radionecrosis 8 months after completion of radiotherapy. The remaining nine patients were alive at a mean follow-up of 28 months (14 to 50 months). Recurrent disease developed within a bed of severe radionecrosis in two patients at 13 and 47 months after completion of radiotherapy. The remaining seven patients have remained without evidence of recurrent disease. Of the 10 total patients severe radionecrosis developed in six at a median of 8.5 months (6 to 26 months) after radiotherapy. We conclude from our data that the use of interstitial needles, mainly combined with external radiotherapy, for the treatment of locally advanced primary or recurrent vulvar and introital malignancy is highly effective but also highly morbid.

Adult↗

Treatment of advanced gynecologic malignancies with intraarterial chemotherapy and accelerated fractionation radiation therapy: a preliminary report.

The results of a pilot study employing the administration of intraarterial chemotherapy and accelerated fractionation radiotherapy for advanced gynecologic malignancies are reported. The protocol consisted of three treatment sessions every 3 to 4 weeks. Each session consisted of bilateral or unilateral catheterization of the hypogastric artery with the infusion of cisplatin 100 mg/m2 on Day 1 and 2-deoxy-5-fluorouridine (FUDR) 300 mg/m2 on Day 2. An accelerated fractionation schedule of external-beam radiation was begun on Day 1 consisting of 200 rads twice daily for 4 days (1600 rads per session). Eight patients entered the protocol, and seven completed external-beam radiotherapy. Five completed three intraarterial sessions, and three, two sessions. Five of seven evaluable patients had a complete local response. Local control was sustained fom 6 to 24 months in four patients. Complications included three sensorimotor neuropathies, one clinically insignificant catheter-related thrombosis, and three clinically significant radiation injuries. This multimodality treatment for locally advanced gynecologic tumors appears feasible with modification, and continued work exploring this approach is encouraged.

Antineoplastic Combined Chemotherapy Protocols↗

Variability in the fibrinogen and von Willebrand factor content of cryoprecipitate. Implications for reducing donor exposure.

Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor (vWF). The minimum acceptable content of Factor VIII is prescribed, but no attempt is made to optimize, standardize, or assess the content of fibrinogen or vWF in cryo. If reasonably accurate information on the composition of cryoprecipitate were available, the physician could calculate an appropriate dose of cryo, thus avoiding unnecessary donor exposures and waste of product. This study was designed to measure the functionally active vWF and fibrinogen in cryoprecipitate prepared by three techniques in an attempt to optimize the yield of these hemostatically important components, and to obtain accurate information on the composition of the product. Cryoprecipitate was made from 82 units of fresh frozen plasma (FFP) as follows: (1) most of the supernatant plasma was expressed from "dry" cryo; (2) about 15 mL of plasma was left in each "regular" unit; and (3) "overnight" units were made from FFP thawed overnight in a refrigerator rather than in a 4 degrees C water bath as for the dry and regular units. Dry, regular, and overnight units had volumes of 8.8 +/- 1.5, 16.6 +/- 3.9, and 15.1 +/- 2.4 mL/bag, respectively. Dry cryoprecipitate units had significantly less fibrinogen and vWF than regular or overnight units. The vWF multimer pattern for all three types of cryoprecipitate was indistinguishable from that of normal pooled plasma. Thus, the amount of plasma expressed during preparation has a significant impact on the vWF and fibrinogen content of the resulting product. The amounts of these clinically important proteins should be assayed as a step toward rational determination of optimal cryoprecipitate doses in specific clinical settings.

Blood Preservation↗

Vibrio cholerae bacteremia associated with gastrectomy.

Bacteremia due to Vibrio cholerae is rare. Each of 15 cases previously reported in the English language literature occurred in the setting of immune deficiency. We describe an instance of non-serogroup O1 V. cholerae septicemia in an otherwise healthy patient. Susceptibility to such infection may have been enhanced by a prior gastrectomy for duodenal ulcer.

Cholera↗

Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise.

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.

Blood Pressure↗

[Consequences of late diagnosis and long-term conservative treatment of patients with congenital heart defects].

Of adult patients of the Cardiac Defects Clinic, National Institute of Cardiology (in Warsaw) we can distinguish several groups of patients with congenital heart defects among which those who were diagnosed after the age of 18 or those who despite of early and correct diagnosis, not underwent surgery on the childhood due to many reasons. In this paper we analyzed the group of 218 patients treated in our clinic between 1981-1987; 103 women aged 13-64 (mean-32 years) and 115 men aged 15-58 (mean-28 years). We classified congenital heart defects into 6 group: ASD, VSD, Tetralogy of Fallot, Persistent Ductus Arteriosus, Coarctation of Aorta and others (19.2%). We classified the range of health care before admission to our Department into the following categories: cardiosurgery (palliative or total correction); no therapy after congenital heart defects diagnosis; medical treatment after diagnosis; admission to our clinic immediately after the diagnosis of a heart defect. We compared that range of health care with qualifications of our Institute-(1. qualification for operation, 2. contraindication for operation, 3. operation unnecessary as the defect is not significant). We conclude basing on our results that, late diagnosis of a congenital heart defect does not finally effect on cardiosurgery possibilities. the majority of patients with C.H.D. have been waiting for many years for a specialist diagnosis and optimal therapeutic decision. long term conservative therapy of the patients with C.H.D. significantly reduces the changes of surgical correction.

Adolescent↗

[Effect of coronary disease risk factors on the progression of coronary arteriosclerosis].

UNLABELLED: A group of 43 patients (pts) from a larger group 451 pts with coronary artery disease (CAD) confirmed by coronary angiography were recatheterized because of deterioration of symptoms. After the first angiography patients had no indications to coronary artery bypass grafting (CABG) or gave no consent to surgery. The group comprised 3 women and 40 men aged 27 to 62 years (mean age 45 +/- 8 years). The mean interval between coronarography was 35 +/- 22 months. Four independent reviewers evaluated 15 segments of coronary arteries according to American Heart Association. The coronary lesions were scored on the basis of reduction in luminal diameter as follows: 0 point = 0-29%, 1 = 30-49%, 2 = 50-69%, 3 = 70-98%, 4 = 90-99%, 5 = 100% occlusion. The influence of the following risk factors on the progression was evaluated: age, sex, hypertension, diabetes, lipid disturbances, smoking, hyperuricaemia, family history. The patients were divided into 3 groups: group I--no or slight progression (0 to 4 points) in two successive coronary angiographies, group II--moderate progression (5 to 9 points) and group II--significant progression (10 points or more). The number of patients in these groups was 14, 12 and 17 respectively. In such isolated groups, the clinical events were compared: unstable angina, myocardial infarctions, need for CABG, cardiac deaths within follow-up period. The ejection fraction of the left ventricle was also evaluated. STATISTICAL ANALYSIS: was conducted by multiple regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗