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Biomedical subjects

M Kahn

Publications and source records attributed to M Kahn.

At least 73 records · Page 4Linked to original sources
PubMed1991

Digitalis and beta-blocking agents: effects on depression following myocardial infarction.

Depression is frequently seen in patients following myocardial infarction (MI), many of whom are receiving digitalis glycosides, beta-blockers, or other agents that may exert central nervous system (CNS) effects. In a prospective study of the clinical significance of post-MI depression, 335 patients were assessed using a standardized diagnostic interview for depression at 8 to 10 days, and 190 were reinterviewed at 3 to 4 months. Patients prescribed digitalis, beta-blockers, or other cardioactive medications at hospital discharge were identified. Logistic regression analyses were performed to determine the contribution of these agents to depression at 3 to 4 months, controlling for medical and sociodemographic factors as well as for baseline depression. Treatment with digitalis predicted depression at 3 to 4 months (p less than 0.05); no other medications, including beta-blockers, predicted depression (p greater than 0.10). Digitalis may have CNS effects that contribute to depression post-MI and this finding should be considered in the differential diagnosis of depression in cardiac patients.

Adrenergic beta-Antagonists↗
PubMed1991

Interval gangrene of the lower extremity: a complication of vascular surgery.

Interval gangrene, segmental ischemic necrosis proximal to a functioning distal anastomosis, is a rare complication after successful peripheral vascular reconstruction. Previous reports have demonstrated the gravity of this event in that major limb amputation was required in all cases. Two cases are presented to emphasize the need for maintaining segmental collateral circulation after successful distal extremity bypass. Despite a satisfactory result after distal (inframalleolar) bypass of a popliteal aneurysm, one patient had progressive ischemic gangrene of the upper leg and eventually required amputation. The contralateral limb was successfully managed by distal ligation of the superficial femoral artery, which maintained collateral flow from the proximal superficial femoral artery to the knee and leg. The second patient required a microvascular free flap to replace tissue loss and provide vascular graft coverage after initial multiple bypass failures and a final successful remote reconstruction to the dorsal artery of the foot that excluded the popliteal-crural collateral network. Patients with inadequate collateral circulation or disruption of the profundus or geniculate collateral pathways may require revascularization of sequential vascular beds. Recognition of the potential for interval gangrene is essential since the likelihood of its occurrence will increase in proportion to the number of distal bypasses being performed for limb salvage. Although adjunctive procedures will not completely eliminate the possibility of interval gangrene, awareness of this phenomenon with attention to the segmental collateral circulation can decrease the incidence of its occurrence.

Adult↗
PubMed1991

Design and synthesis of nonpeptide mimetics of jaspamide.

Jaspamide is a novel metabolite of mixed peptide/polyketide biosynthesis that was isolated from sponges of the genus Jaspis, and that has been reported to exhibit both insecticidal and antifungal activity. We have evaluated three nonpeptide mimetic designs, and have synthesized a nonpeptide mimic of the proposed bioactive region to investigate the structure activity relationship. Structural investigations of potential mimetics, utilizing molecular modeling in conjunction with spectroscopic and crystallographic data, indicate that positioning of the critical functional groups in two mimetics corresponds closely to that observed in jaspamide, and that the flexibility of mimetic 4 approximates that of jaspamide. Initial biological evaluation suggests that lactam mimetic 4 exhibits a biological profile similar to jaspamide.

Antifungal Agents↗
PubMed1991

Infrapopliteal prosthetic graft patency by use of the distal adjunctive arteriovenous fistula.

From November 1979 through December 1989, 210 distal arteriovenous fistulas were constructed as adjuncts to tibial and peroneal vascular reconstructive procedures in 203 patients threatened with limb loss. Two-year cumulative patency rates were calculated by grouping patients on the basis of changing indications in sequential time periods: group 1 (n = 61): 1979 to 1983, 18%; group 2 (n = 80): 1983 to 1986, 33%; group 3 (n = 69): 1986 to 1989, 44%. Although the therapeutic results observed in these groups are not statistically comparable, they show a perceptible trend. Postoperative arteriography showed that flow is prograde in the distal vessels beyond the distal arteriovenous fistula. Graft surveillance by duplex ultrasonography also confirmed that flow in the distal arteries is prograde and that "steal" does not occur. Peak systolic velocity (174 +/- 38 cm/sec) and mean velocity (92 +/- 23) flow rates are increased in grafts with patent distal arteriovenous fistulas compared to those bypasses with closed distal arteriovenous fistulas (p less than 0.01). There were no differences in the flow measurements for the arteries beyond the distal anastomoses and distal arteriovenous fistulas, confirming the prograde nature of the distal flow. In 22 patients analysis of graft and fistula patency by duplex sonography showed that one fourth of all grafts were patent without fistulas at 1 and 2 years after operation. Alternatively, 68% of patent grafts at 1 year had patent fistulas and 58% had patent fistulas at 2 years. We conclude that the distal arteriovenous fistula will increase graft flow and simultaneously prevent distal arterial overload without causing "steal." This technique should be considered whenever a prosthetic graft is necessary for crural reconstruction and only in selected instances of revascularization with autologous veins.

Adult↗
PubMed1991

Transmetatarsal amputation: the role of adjunctive revascularization.

Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Epitope mapping and use of anti-idiotypic antibodies to the L6 monoclonal anticarcinoma antibody.

Mouse monoclonal anti-idiotypic antibodies (anti-ids) were raised against L6, a murine IgG2a monoclonal antibody specific for a cell surface antigen expressed by many human carcinomas. Ten distinct anti-ids were generated. Eight anti-ids were shown to inhibit the binding of L6 to its target antigen and were characterized in detail. The heavy and light chain variable region gene segments of the monoclonal antibody L6 linked to human constant regions (chimeric L6) were expressed separately or together, to map the epitopes recognized by the anti-ids. Individual anti-ids were shown to recognize heavy chain, light chain, or combinatorial variable region determinants. Defining these specificities enabled us to select particular anti-ids for assays to monitor the pharmacokinetics of either murine or chimeric L6 antibodies in the circulation of human patients. A quantitative enzyme-linked immunosorbent assay developed with two anti-ids accurately detects less than 5 ng/ml. Anti-ids specific for light chain variable region-encoded determinants were capable of recognizing L6 antigen-binding fragments bound to the surface of human carcinoma cells. These anti-ids can be used to study the binding of chimeric L6 antibody at the surface of tumor cells in histological sections of tumor biopsies.

Animals↗
PubMed1990

Epidural anesthesia as an adjunct to retroperitoneal aortic surgery.

Recent developments in vascular surgery suggest that the retroperitoneal approach to the aorta and the use of epidural anesthesia for lower limb revascularization are associated with decreased morbidity and shorter hospital stays. By combining these principles, we sought to determine if retroperitoneal aortic surgery could be performed under epidural anesthesia and if this might be advantageous. Over a 16-month period, 57 patients underwent aortic surgery via the retroperitoneal (n = 33) or transperitoneal (n = 24) approach. In the former, epidural anesthesia was employed in 10 patients, general anesthesia in 3, and combined epidural anesthesia and general anesthesia in the remaining 20. In the transperitoneal group, general anesthesia was employed in 21 patients and combined epidural anesthesia and general anesthesia in 3. Both groups were similar in age and gender, but risk factors were predominant in the retroperitoneal group. With the exception of one death due to aspiration, there were no significant differences between the transperitoneal and retroperitoneal groups with respect to overall morbidity, pulmonary complications, and length of stay in the intensive care unit and hospital. Despite these findings, we favor the combination of epidural and general anesthesia for retroperitoneal aortic surgery. Morbidity was significantly decreased (p less than 0.05) in low-risk retroperitoneal patients when combined epidural anesthesia and general anesthesia were employed.

Adult↗
PubMed1990

Differential extraction of keratin subunits and filaments from normal human epidermis.

We have investigated keratin interactions in vivo by sequentially extracting water-insoluble proteins from normal human epidermis with increasing concentrations of urea (2, 4, 6, and 9.5 M) and examining each extract by one- and two-dimensional gel electrophoresis, immunoblot analysis using monoclonal anti-keratin antibodies, and EM. The viable layers of normal human epidermis contain keratins K1, K2, K5, K10/11, K14, and K15, which are sequentially expressed during the course of epidermal differentiation. Only keratins K5, K14, and K15, which are synthesized by epidermal basal cells, were solubilized in 2 M urea. Extraction of keratins K1, K2, and K10/11, which are expressed only in differentiating suprabasal cells, required 4-6 M urea. Negative staining of the 2-M urea extract revealed predominantly keratin filament subunits, whereas abundant intermediate-sized filaments were observed in the 4-urea and 6-M urea extracts. These results indicate that in normal human epidermis, keratins K5, K14, and K15 are more soluble than the differentiation-specific keratins K1, K2, and K10/11. This finding suggests that native keratin filaments of different polypeptide composition have differing properties, despite their similar morphology. Furthermore, the observation of stable filaments in 4 and 6 M urea suggests that epidermal keratins K1, K2, and K10/11, which ultimately form the bulk of the protective, nonviable stratum corneum, may comprise filaments that are unusually resistant to denaturation.

Actin Cytoskeleton↗
PubMed1990

Everted cervical vein for carotid patch angioplasty.

Because of the theoretic benefits of autologous vein we undertook an investigation to evaluate cervical veins (facial, external jugular) as patch material after carotid endarterectomy. A device that stimulated both circumferential fixation by sutures and radial tension exerted on in vivo patches was constructed to measure burst strength of tissue. Mean bursting pressure for groin saphenous vein (n = 10) was 94.5 +/- 15.1 pounds per square inch (psi), 75.5 +/- 8.9 psi for ankle saphenous vein (n = 10), 83.3 +/- 14.5 psi for everted (double layer) cervical vein (n = 5) and 10 +/- 3.3 psi for single layer cervical vein (n = 5). No significant differences between saphenous vein at any level and everted (double layer) cervical vein, but all were significantly different from single layer cervical vein (p less than 0.05). From June 1987 through November 1989, 19 patients underwent 21 carotid endarterectomies complemented with adjunctive everted cervical vein patch angioplasty. Indications for surgery were asymptomatic stenosis (53%), transient ischemic attack (29%), and cerebrovascular accident with recovery (18%). All patients were studied after surgery with duplex scanning. Asymptomatic recurrent stenosis was observed in one patient. Transient hypoglossal nerve dysfunction occurred in one other patient. One postoperative death occurred as a result of massive aspiration. These results indicate that everted cervical vein is comparable to the saphenous vein in resistance to bursting and can yield similar results as patch material after carotid endarterectomy. Accordingly, saphenous vein can be spared and lower extremity incisions avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Penetrating the conjunctival barrier. The role of molecular weight.

Dinitrophenyl (DNP) derivatives of various molecular weights were tested for their ability to elicit ocular anaphylaxis after topical application to the eye of immunized animals. Adult male Sprague-Dawley rats were immunized by intraperitoneal injection of DNP-Ascaris suum extracts and alum and were then skin-tested with DNP-bovine serum albumin on day 13 post-immunization to assess their sensitivity to the DNP hapten. On day 14, animals were challenged topically with DNP derivatives in one eye; PBS was applied to the contralateral, control eye. Animals were evaluated clinically, and ocular tissues were processed for histologic evaluation. The compounds used for topical ocular challenge included the DNP derivative of egg albumin (MW 43,500 D), soybean trypsin inhibitor (MW 20,080 D), insulin (MW 5733 D), B-chain insulin (MW 3496 D), and lysine (MW 478 D). Only di-DNP-lysine elicited clinical signs of redness, edema, and tearing and histologic evidence of mast cell degranulation. None of the other compounds, tested in solutions of either equal numbers of milligram per milliliter or equimolar concentrations, elicited ocular anaphylaxis after topical application. A compound of low molecular weight, less than 3496, is needed to elicit ocular anaphylaxis when applied topically.

Administration, Topical↗
PubMed1989

The use of oncofetal ferritin-bearing lymphocytes as a marker for the screening, diagnosis, and follow-up of patients with early breast malignancy screening of 3400 women.

The potential of using a blood test enumerating oncofetal ferritin-bearing lymphocytes (FBL) as a biomarker for early breast cancer was further explored. Nine hundred women attending a high-risk breast cancer clinic and 2500 normal-risk women were physically examined and their blood drawn for FBL determination using a newly developed radioimmunoassay. The FBL test results were compared to clinically or histopathologically diagnosed breast disease and to known breast cancer risk factors. A gradual increase in the mean FBL ratio was seen from normal risk disease-free women to those with in situ or early stage breast cancer. The percentage of women with positive FBL was 13.6% for the normal risk group, 19% and 25.7% for clinically and histopathologically diagnosed benign breast disease, respectively, and 100, 77.8, and 66.7% for in situ, Stage I, and Stage II breast cancer, respectively. In locally advanced disease (Stage III) the percentage of positive women was only 17.2%. It was further found that a negative FBL result in known breast cancer patients at Stage I, II of the disease was a bad prognostic marker indicating a shorter disease-free survival. The follow-up of patients after surgery by periodical clinical examination and the FBL test revealed that the positive FBL was declining after removal of the precancerous or malignant tumor and that it was highly sensitive (100%) in predicting tumor development and recurrence. Using a logistic regression analysis, an FBL-positive test indicated a significant association with risk of early breast cancer (odds ratio = 2.9; 95% confidence interval = 1.4-5.8). Being a measure of the immune response the positive FBL was associated with early breast cancer and good prognosis. Since patients with locally advanced cancer and poor prognosis were FBL negative but such patients were shown to have increased serum ferritin levels. It is suggested to use the FBL and serum ferritin assays for screening and diagnosis of breast cancer.

Antigens, Neoplasm↗
PubMed1989

Monoclonal antiidiotypic antibodies related to the p97 human melanoma antigen.

We have made monoclonal antiidiotypic antibodies (Ab2) relating to the p97 antigen of human melanoma. This was accomplished by immunizing BALB/c mice with 96.5, a monoclonal antibody (MAb) specific for epitope p97a, hybridizing their spleen cells with NS-1 myeloma cells, and selecting for hybridomas making antibody binding to Fab fragments prepared from MAb 96.5 (Fab 96.5). The Ab2 were tested for binding to Fab 96.5, as well as for their ability to inhibit the binding between MAb 96.5 and p97. Three monoclonal Ab2 were identified which competitively inhibited the binding between p97 and MAb 96.5 when injected into either BALB/c or C3H/HeN mice; two of them induced Ab3 which expressed the same idiotype as MAb 96.5 and which were specific for p97. These two Ab2 thus appear to functionally mimic p97. They were, however, unable to induce delayed-type hypersensitivity to p97 and to protect mice against transplants of p97-positive mouse melanoma cells, suggesting that the epitope recognized by MAb 96.5 may not be a target for cell-mediated rejection of tumors.

Animals↗
PubMed1989

Transfected mouse melanoma lines that express various levels of human melanoma-associated antigen p97.

The gene for the human melanoma-associated antigen p97 has been introduced by cDNA transfection into cells from clone M2 of the K1735 mouse melanoma, which metastasizes to the lung when injected iv into syngeneic C3H/HeN mice. Tumor clones were established from the transfected cells and found to differ in the level of p97 expression. Their outgrowth in immunocompetent syngeneic mice was shown to inversely correlate with p97 antigen expression, and lines that express higher p97 levels elicited a stronger delayed-type hypersensitivity response when injected into the footpads of mice immune to p97. Five clones which expressed very high levels of p97 failed to grow in immunocompetent C3H/HeN mice while they formed tumors in nude (nu/nu) mice. The highest expressing clone, 2A, grew slightly faster than any of the other clones when cultured in vitro. Since several of the transfected clones were found to express a stable level of p97 and have consistent in vivo growth behavior, they provide a useful model for various forms of antigen-specific active and passive immunotherapy with the same agents as those intended for human application.

Animals↗
PubMed1989

Synchronous intrauterine and ectopic pregnancy associated with clomiphene citrate.

Although synchronous intrauterine and ectopic pregnancies associated with the use of clomiphene citrate for infertility are rare, the actual incidence might, in fact, be considerably higher than previously thought. The cornerstone for ruling out an extrauterine gestation is the presence of sonographic evidence of an intrauterine pregnancy, as the possibility of concomitant intrauterine and extrauterine gestation is perceived to be statistically rare. This has resulted in an unacceptably high incidence of negative ultrasound interpretations. During a recent 12 month period, four women treated with clomiphene citrate for infertility were diagnosed as having concomitant intrauterine and ectopic pregnancies. Three had pelvic sonograms that were erroneous for the extrauterine component. However, successful evacuation of the products of ectopic gestation was performed in each, despite an immediate preoperative false-negative ultrasound report. Three of the women delivered healthy normal infants at full term, and the fourth woman spontaneously aborted the products of the concomitant intrauterine gestation. All four did well postoperatively, and no gross complications were encountered. Reassessment of ultrasound diagnostic criteria and the use of more sensitive methods, such as endovaginal ultrasound in high risk patients, are indicated for any symptomatic patient using clomiphene citrate for infertility. Awareness of the prevalence of this entity and the limitations of ultrasound will lead to prompt intervention and improved survival rates.

Clomiphene↗