Fred V. Lucas

Inflammatory carcinoma of the breast

Fifty‐eight patients with clinical inflammatory breast carcinoma and 15 patients with “occult” inflammatory cancer (dermal lymphatic carcinomatosis without clinical inflammation) are grouped and reviewed to determine whether diagnosis is pathologic or clinical. All cases represent a retrospective study of records from the Ellis Fischel State Cancer Hospital, Columbia, Missouri. Lesions of clinically apparent and occult inflammatory carcinoma demonstrate similar gross and microscopic growth patterns, histologic types, axillary involvement and early widespread metastases. Regardless of pathologic evidence of dermal lymphatic tumor, patients with clinical inflammation had rapid deterioration. Cases with only a pathological diagnosis were slightly less fulminant in progression. Either clinical or pathologic criteria justify use of the term “inflammatory breast carcinoma” to indicate short‐term prognosis despite available treatment.

Thrombolysis of peripheral arterial bypass grafts: Surgical thrombectomy compared with thrombolysis ☆ ☆☆: A preliminary report

Twenty-two patients were selected from a group of 33 patients who underwent recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis for thrombosed infrainguinal bypass grafts of the lower extremity and were compared with 38 matched patients who had undergone surgical thrombectomy during the same period. The proportion of persons with diabetes mellitus, smokers, and types of bypass grafts was similar in both groups. More patients in the rt-PA-treated group had hypertension (p = 0.01). To evaluate the different lengths of follow-up, Kaplan-Meier survival analysis was used with a log-rank test to compare the proportion of persons with patent grafts in the two treatment groups. At 30 days, 86% of the rt-PA-treated grafts were still patent compared with 42% of the surgically treated grafts (p = 0.001). When risk factors on the Kaplan-Meier curves were compared, there was no statistical difference with regard to graft patency among the groups. According to simultaneous Cox regression analysis, no risk factor was significantly associated with graft patency. When amputation was evaluated between treatment groups simultaneously with other risk factors in a logistic regression analysis, smoking and age of the graft were marginally significant (p = 0.07), whereas all other factors were clearly not significant. In 91% of the rt-PA-treated patients, a secondary surgical procedure was required to maintain patency of the graft segment. Eighty-nine percent of the surgically treated patients required similar graft revisions. Two patients in the surgical group and one patient in the rt-PA-treated group had major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructure of the human endometrial glandular cell during the menstrual cycle.

Abstract The ultrastructure of endometrial stromal cells of normal healthy women in reproductive age is described on days 5, 10, 15, 20, and 25 of the menstrual cycle. The stromal cells, in the course of the normal menstrual cycle, undergo distinctive ultrastructural changes that can be correlated with states of proliferation, differentiation, and maturation. On day 5, the stromal cells are essentially immature, resembling stem cells. On day 10 the cells show the beginning of differentiation toward a fibroblast. Day 15 is characterized by the highest rate of proliferation of the cycle. By day 20 evidence of proliferation has disappeared and most cells now present a fully differentiated fibroblastic morphology. Day 25 demonstrates full maturation of the superficial stromal cells to become predecidual cells.

Intravenous nitroglycerin-induced heparin resistance :a qualitative antithrombin III abnormality

An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.

Retained mucosa after double-stapled ileal reservoir and ileoanal anastomosis

A study was undertaken to assess the incidence of inflammation and dysplasia in retained mucosa after double-stapled ileoanal reservoir (IAR) for mucosal ulcerative colitis (MUC). Between September 1988 and February 1992, 56 patients with MUC underwent an IAR. Forty-five patients had a double-stapled IAR (DS-IAR), seven patients had a transanal pursestring stapled IAR (PS-IAR), and four patients had a PS-IAR with mucosectomy. Distal donuts obtained from the stapled IAR were submitted for pathologic review in 55 patients. Nine patients had only small bowel, connective tissue, and/or muscle noted on review. Mucosa was qualified as squamous epithelium (SE), transitional epithelium (TE), or columnar epithelium (CE). All samples were examined for evidence of inflammation and dysplasia. Four patients had SE only, one patient had TE, and 18 had CE. In addition, three patients had SE and CE, seven patients had SE and TE, two patients had CE and TE, and nine patients had all three types. The distance from the dentate line to the anastomosis ranged from 0 to 2.5 cm (mean, 1 cm). In 19 patients (35 percent), the distal donut revealed MUC. Of these 19 patients, six had persistent MUC (43 percent) at the time of subsequent biopsy. An additional four patients had MUC evident on follow-up biopsy but not on distal donuts; two of these four patients had no mucosa in their distal donuts. Only one of the patients with evidence of MUC on donuts and/or biopsy experienced any symptoms referable to active MUC (1.8 percent). None of the specimens examined had any evidence of dysplasia. In 31 patients, no MUC was present in the initial donuts or follow-up biopsies. Although the double-stapled technique appears safe, periodic monitoring is suggested.

Platelet Glutathione and Thromboxane Synthesis in Diabetes

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 ± 0.73 μg/109 platelets, mean ± SD) was significantly (P < 0.001) lower than in platelets from control subjects (10.10 ± 1.58 μg/109 platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P < 0.001) more TXB2 was formed in PRP from diabetic subjects (344 ± 87 ng/2.5 × 108 platelets) than in PRP from control subjects (132 ± 35 ng/2.5 × 108 platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 ±117 pg/ml) in comparison with control subjects (187 ± 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.

Peripheral artery and bypass graft thrombolysis with recombinant human tissue-type plasminogen activator

Recombinant tissue-type plasminogen activator (t-PA) is a DNA-synthesized thrombolytic agent recently approved for clinical trials. We present the results of t-PA infusions in 18 patients with thrombosed peripheral arteries (12 patients) and peripheral bypass grafts (six patients). The duration of occlusion ranged from 1 to 21 days (mean, 6.8 days). Infusions of t-PA were done by way of an intra-arterial approach at a dose of 0.1 mg/kg/hr. All patients demonstrated thrombus lysis angiographically. Fifteen of 18 (83%) had clinical as well as angiographic improvement. Secondary procedures to maintain patency of the arterial segment were required in seven patients. No complications occurred that were related to the t-PA infusion. No significant prolongation of the prothrombin, thrombin, or activated partial thromboplastin times occurred. At the end of t-PA infusion, the mean circulating fibrinogen level was 59% of the starting value. The therapeutic use of t-PA is still in its preliminary stages and the efficacy and safety of this promising agent need to be further established. From our early experience with t-PA, it appears to be safe as well as effective.

The contrecoup phenomenon: Reappraisal of a classic problem

We describe briefly and comment upon the salient strengths and limitations of the major published theories that purport to explain the mechanism of contrecoup cerebrocortical contusions. Through the application of mechanical principles, we then present a modification, clarification, and expansion of selected aspects of several theories. Our final formulation emphasizes the injurious potential of nonuniform compressive stress and the relationship between brain lag and rotationally induced injury. The resulting theory remains faithful to the laws of physics while explaining the location and distribution of cerebrocortical contusions opposite the site of a moving head impact.

Treatment of acute focal cerebral ischemia with prostacyclin.

The object of this investigation was to study the effects of prostacyclin (PGI2) upon the evolution of acute focal cerebral ischemia in the cat. Twenty-five fasted adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion. Eleven cats received an intracarotid infusion of PGI2 in buffered saline pH 10.5 (100 ng/kg/min at 0.01 ml/kg/min), and 11 cats received intracarotid buffered saline pH 10.5 (0.01 ml/kg/min) without therapeutic agents. Treatment with PGI2 was started upon MCA occlusion and continued for 6 hours. Thirty minutes prior to perfusion, the animals were given fluorescein and Evans blue by intravenous injection. The cats were perfused-fixed in vivo with carbon and buffered formalin 6 hours after MCA occlusion. Another 3 cats received tritium labeled intracarotid PGI2, and peripheral venous samples were collected and assayed for PGI2 plasma levels. Mean arterial pressure was stable in PGI2 treated animals during 6 hours of MCA occlusion, while untreated cats had significant progressive hypertension during that period. The rCBF (measured by the intracarotid 133Xe method) decreased markedly in all animals immediately upon MCA occlusion. However, untreated animals had a significant progressive improvement in rCBF during the occlusion period, while PGI2 treated animals had no such improvement. Quantitative EEG changes, gross edema, areas of fluorescein extravasation, patterns of carbon perfusion, and infarct size were not significantly different in the two groups. While most untreated animals had marked Evans blue extravasation after 6 hours of MCA occlusion, most PGI2 treated animals had no such extravasation, indicating some protection of the blood-brain barrier in these animals.

The structure of rat liver mitochondria: A reevaluation

Summary Mitochondria have been considered to have single spherical or tubular shape. Recently a new model has been proposed for the structure of yeast mitochondria which suggests that there is a single, branched, tubular mitochondrion per cell. Using the technique of serial sectioning, we present evidence showing that some, but not all mitochondria of normal adult rat liver have a branched, tubular structure. These observations should lead to a reevaluation of current concepts regarding mitochondrial function and biogenesis.