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Biomedical subjects

H L Evans

Publications and source records attributed to H L Evans.

At least 37 records · Page 2Linked to original sources

Adrenal cortical neoplasms. A study of 56 cases.

Fifty-six cases of adrenal cortical neoplasm with a minimum of 5 years follow-up are presented: 48 carcinomas and 8 adenomas. Adenomas typically had a maximal mitotic rate of fewer than 2 mitotic figures per 10 high-power fields (all cases), a prominent small nest growth pattern (7 cases), predominantly clear or foamy cytoplasm (6 cases), and no tumor necrosis (all cases), whereas carcinomas were characterized by at least 4 mitotic figures (often many more) per 10 high-power fields in the most active area (all cases), lack of a significant small nest growth pattern component (45 cases--solid or trabecular growth most common), at least a considerable proportion of cells with eosinophilic cytoplasm (all cases), and tumor necrosis (45 cases). Carcinomas were almost always larger than adenomas, but two adenomas (5.9 cm and 7 cm) overlapped in size with the four smallest carcinomas (5.5 cm, 6 cm, 7 cm, and 7 cm, respectively). The patients with adenomas were older on the average than those with carcinomas (median 58 years, range 31-71 years versus median 41 years, range 5 months-66 years). Two adenomas and 19 carcinomas were functional. No patient with adenoma had recurrence of tumor after excision, whereas all but nine carcinoma patients died of tumor, after 1 to 183 months. Among carcinoma patients, survival was significantly shorter when distant metastases were manifest at diagnosis (P = .0003). There was a trend toward shorter survival with higher mitotic rates and functional tumors, but neither these nor any other parameter had a statistically significant relationship to survival or tumor behavior when presence/absence of metastases at diagnosis was taken into account.

Adolescent↗

Encapsulated columnar-cell neoplasms of the thyroid. A report of four cases suggesting a favorable prognosis.

Four encapsulated thyroid neoplasms with columnar-cell features were studied. The patients were a 29-year-old man and three women aged 42, 60, and 83 years. The tumors measured from 1.2 to 8.0 cm in maximum dimension. All were completely surrounded by a thick capsule; three demonstrated invasion into the capsule (but no farther), whereas one (from the 60-year-old woman) did not. In addition to columnar-cell areas, all the neoplasms had areas with follicular and solid growth, in varying proportions. Although the growth pattern in the columnar-cell zones was usually papillary, nuclear characteristics of papillary carcinoma were not present in these areas or elsewhere. Follow-up on the four patients was 112, 51, 112, and 29 months, respectively, and none had any evidence of recurrence or metastasis. The findings suggest that encapsulated columnar-cell thyroid tumors have a much more favorable prognosis than those that are unencapsulated and invasive into adjacent thyroid or extrathyroid tissue.

Adult↗

Metastasizing cellular dermatofibroma. A report of two cases.

Two cases of metastasizing cellular dermatofibroma (cutaneous fibrous histiocytoma) are presented. The first patient, an 18-year-old man, had a nodule excised from his right upper thigh. He developed three local recurrences at 1.5, 2, and 2.5 years and metastasis to inguinal lymph nodes. He underwent lung segmentectomies for metastases 1.5 and 4 years later and was alive with no evidence of tumor at latest follow-up, which was 15 months after the last surgery. The second patient, a 33-year-old man, had a nodule removed from his right posterior neck. The tumor recurred 3 months later and was reexcised. Right cervical lymph node metastases were excised at 7 and 8 years. A year later, a right cervical lymph node dissection yielded one positive node of 35, and multiple metastases were excised from the right lung. The patient was alive with lung metastases 6 years later, which was the latest follow-up. Grossly, both tumors were single 2 cm nonulcerated dermal-subcutaneous nodules. Histologically, they were characteristic of cellular dermatofibroma; they were composed of plump to spindled "fibrohistiocytic" cells arranged in a storiform pattern and had areas of hemorrhage, hemosiderin, and infiltration between dermal collagen bundles peripherally. Recurrences and metastases were histologically similar except that lung metastases were cystic. The alternative diagnosis of angiomatoid malignant fibrous histiocytoma was considered for these two cases but was excluded because the tumors were partly dermal, had a well-defined storiform pattern, and lacked large blood lakes, multinodularity, a fibrous pseudocapsule, and surrounding chronic inflammation. We conclude that dermatofibromas can rarely metastasize. Risk factors for metastasis may include relatively large size, high cellularity, and local recurrence. Judging from these two cases, metastasizing dermatofibromas behave in an indolent manner.

Adolescent↗

Lead (Pb+2) promotes apoptosis in newborn rat cerebellar neurons: pathological implications.

Despite mandated reduction in environmental lead (Pb++), such exposure still poses a public health hazard for children, with devastating effects on CNS development. To replicate aspects of this neurotoxicity, we used cultured granule cells from newborn rat cerebella to study whether apoptotic or necrotic death is the major consequence of exposure to low micromolar concentrations of Pb++. At a low dose, 1 microM (EC50 approximately equal to 10 microM), Pb++ does not affect glutamate-induced neuronal necrosis but promotes neuronal apoptosis, as characterized morphologically by cell shrinkage and chromatin condensation, biochemically by the typical internucleosomal DNA fragmentation and functionally by dependence on new synthesis of macromolecules (cycloheximide- and actinomycin D-sensitive). The low micromolar doses of Pb++ that promote apoptosis are well within the blood level range reported to impair CNS function in children and to alter synaptogenesis in the neonatal rat brain. Thus these in-vitro results suggest that the highly neurotoxic action of Pb++ in the developing CNS of children might depend on a facilitation of apoptosis. The Pb+2-elicited potentiation of neuronal apoptosis is attenuated by treatment with the voltage-sensitive Ca+2 channel agonist Bay K8644, which suggests the possible use of this agonist for treatment of the neurotoxic effects of Pb++.

Animals↗

Exposure to methyl mercury results in serum autoantibodies to neurotypic and gliotypic proteins.

Environmental exposure to methyl mercury (MeHg) continues to pose a threat to humans, making early detection of neurotoxic effects a pressing concern. An enzyme-linked immunosorbent assay (ELISA) to measure serum autoantibodies (Ig) to neurotypic and gliotypic proteins [neurofilament triplet (NF68; NF160; NF200), myelin basic protein (MBP) and glial fibrillary acid protein (GFAP)] as markers of subclinical neurotoxicity was developed and tested in Fisher 344 rats exposed orally to 16 or 32 ppm MeHg. Both levels of MeHg resulted in serum Ig to all 5 proteins, not normally seen in controls. For anti-NFs and anti-GFAP, IgM isotype predominated significantly (p < 0.05) over IgG.Ig for MBP were of the IgG isotype, IgM were not detected. Significant differences (p < 0.05) between 16 and 32 ppm MeHg in levels of anti-NF 68 and GFAP, IgM, were evident at 7 days of exposure, but not at 14 days. Anti-NF 160, IgM, was significantly (p < 0.01) elevated in rats exposed to 32 ppm vs 16 ppm at 14 days. However, at both dose levels anti-NF 68 titers were the most elevated of the three NF proteins (p < 0.0001). For anti-NF 200 and anti-MBP it was the IgG isotype that was significantly (p < 0.01) elevated in the 32 ppm group at 7 days. GFAP levels as a marker of neurotoxicity were determined in the cortex, hippocampus and cerebellum. Exposure to 32ppm MeHg resulted in decreased (p < 0.05) levels in the cortex at 14 days. Both levels of MeHg resulted in increased GFAP in the cerebellum at 14 days. This study suggests that assay of autoantibodies against nervous system proteins may provide a means of assessing the early neurotoxic effects of environmental MeHg exposure.

Animals↗

Exposure to methylmercury results in serum autoantibodies to neurotypic and gliotypic proteins.

Environmental exposure to methylmercury (MeHg) continues to pose a threat to humans, making early detection of neurotoxic effects a pressing concern. An enzyme-linked immunosorbent assay (ELISA) to measure serum autoantibodies (lg) to neurotypic and gliotypic proteins [neurofilament triplet (NF68; NF160; NF200), myelin basic protein (MBP) and glial fibrillary acid protein (GFAP)] as markers of subclinical neurotoxicity was developed and tested in Fisher 344 rats exposed orally to 16 or 32 ppm MeHg. Both levels of MeHg resulted in serum lg to all 5 proteins, not normally seen in controls. For anti-NFs and anti-GFAP, lgM isotype predominated significantly (p < 0.05) over lgG. lg for MBP were of the lgG isotype, lgM were not detected. Significant differences (p < 0.05) between 16 and 32 ppm MeHg in levels of anti-NF 68 and GFAP, lgM, were evident at 7 days of exposure, but not at 14 days. Anti-NF 160, lgM, was significantly (p < 0.01) elevated in rats exposed to 32 ppm vs 16 ppm at 14 days. However, at both dose levels anti-NF 68 titers were the most elevated of the three NF proteins (p < 0.0001). For anti-NF 200 and anti-MBP it was the lgG isotype that was significantly (p < 0.01) elevated in the 32 ppm group at 7 days. GFAP levels as a marker of neurotoxicity were determined in the cortex, hippocampus and cerebellum. Exposure to 32ppm MeHg resulted in decreased (p < 0.05) levels in the cortex at 14 days. Both levels of MeHg resulted in increased GFAP in the cerebellum at 14 days. This study suggests that assay of autoantibodies against nervous system proteins may provide a means of assessing the early neurotoxic effects of environmental MeHg exposure.

Animals↗

Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma.

BACKGROUND: Because of a tendency for diffuse, clinically undetectable local spread, cutaneous angiosarcoma is difficult to treat with surgery alone. Radiation is a rational treatment modality for this disease, because a wide region of dermis can be treated, whereas the underlying normal tissues are spared. METHODS: The authors retrospectively studied 14 patients with dermal angiosarcoma of the head and neck who were treated with electron-beam radiation from 1970 to 1989. Primary tumors were located in the scalp and forehead (11 patients) and in the upper face (3 patients). Eleven patients presented with multiple foci of disease. Three patients were treated with radiotherapy alone; the other 11 were treated with chemotherapy (10 patients) and/or surgery (7 patients). Surgical excisions were limited procedures for patients whose disease readily could be encompassed; total scalp resections were not performed. Patients were irradiated with a multiple-field electron-beam technique. Six patients presented postoperatively for radiotherapy with no macroscopic disease in the treatment field and were given a median dose of 60 Gy (range, 50-66 Gy) over a median of 40 days (range, 37-43 days). Eight patients were irradiated with clinically evident disease; doses ranged from 55 to 75 Gy over a median of 44 days (range, 33-66 days). RESULTS: Five of the six patients irradiated without clinically detectable disease were controlled in the treatment field, but only two are currently disease free. Of the eight patients irradiated with macroscopic tumor, initial disease recurrence occurred in the radiation field in two patients and at the radiation field margin in three patients. The actuarial 5-year control rates above the clavicles for patients irradiated with and without clinical disease were 24% and 40%, respectively (P = 0.03). The 5-year actuarial incidence of distant metastases for all patients was 63%. The 5-year actuarial survival rate for patients irradiated with and without clinical disease was 13% and 50%, respectively (P = .04). CONCLUSIONS: Radiation is an effective modality for treating local disease, especially when used after surgical resection of macroscopic tumor. Our current strategy is to resect clinically evident tumor in patients presenting with focal, limited disease, and to follow this resection with moderate dose, very wide-field radiation. The survival outcome for patients presenting with diffuse multifocal disease is bleak, but some patients can be controlled infield with radiation. There must be continued efforts to develop effective systemic therapy.

Aged↗

Markers of neurotoxicity: from behavior to autoantibodies against brain proteins.

Evidence of potentially neurotoxic exposures may be obtained in peripheral indicator media, but molecular or cellular evidence of neurotoxic effects has not been as readily available, primarily because the nervous system of living humans is beyond the reach of direct measures. Although there is limited evidence that molecular changes in the blood can provide information about neurotoxicity, several new approaches are being investigated. One is that the immune system may preserve evidence of damage to the nervous system. Debris from damaged cells in the nervous system may present as antigens, giving rise to autoantibodies, which may be detectable in blood for a long time after injury. Progress will depend on more control experiments and clarification of confounding variables. Validation of new molecular markers must go hand in hand with documentation of impaired function, most commonly measured as behavioral or neurophysiological changes. These noninvasive markers will be measured with greater sensitivity and precision, thanks to innovative computer technology. The practical advantages of the new markers may be as important as their contribution to our understanding of the mechanisms by which the nervous system defends against chemical insult.

Autoantibodies↗

Classification and grading of soft-tissue sarcomas. A comment.

A contrary viewpoint concerning certain issues in soft-tissue sarcoma pathology is presented. Three issues emphasized are (1) the role of immunocytochemistry and electron microscopy in diagnosis, (2) the classification of liposarcomas and atypical lipomatous tumors, and (3) the validity and usefulness of histologic grading.

Cell Differentiation↗

Desmoplastic fibroblastoma. A report of seven cases.

Seven cases of desmoplastic fibroblastoma, a distinctive fibrous soft-tissue tumor, are presented. The patients, four men and three women, ranged in age from 25 to 83 years (median 57 years). The tumors were located in the neck (two cases), the upper arm, the forearm, the shoulder, the lateral thigh, and the dorsum of the foot (one case each). Three neoplasms were intramuscular, and four were subcutaneous (two of the latter were directly on top of muscle). Maximum tumor dimension varied from 1.8 cm to 9 cm (median 3.2 cm). Grossly, the lesions were well circumscribed, firm, and white to gray to tan on cut section. Microscopically, they were composed of medium-sized to large "reactive appearing" spindled to stellate fibroblasts sparsely distributed in a fibromyxoid to densely fibrous background; mitotic figures were very rare or absent, tumor necrosis was not seen, and vascularity was low. The tumor border was generally well de-limited, although interdigitation with adjacent muscle or fat was present in areas in some cases. Follow-up ranging from 15 months to 46 months (median 28 months) after excision was available on five patients. No recurrences were observed.

Adult↗

Trimethyl lead neurotoxicity in the rat: changes in glial fibrillary acidic protein (GFAP).

The literature on the toxicology of lead provides little evidence of the neurotoxicity of organic lead compounds. Toxicant-induced changes in the concentration of glial fibrillary acidic protein (GFAP) in the brain may help clarify at which stage of neurotoxicity astrocytes are affected and whether GFAP may provide an index of toxicity. Male F344 rats (> 42 days old) were exposed to 0 (control), 8 or 16 ppm lead as trimethyl lead (TMPb) in drinking water for up to 14 days. Weight Gain was significantly reduced in both exposed groups. Control rats had the expected brain regional pattern of GFAP concentration with the highest in the hippocampus and cerebellum and lowest in the cerebral cortex. The hippocampus was the region very sensitive to TMPb, with increased GFAP in rats exposed to 8 and 16 ppm TMPb with decreases in GFAP in rats exposed to 8 and 16 ppm TMPb for 14 days. There was a significant time-response in rats exposed to 8 ppm TMPb with decreases in GFAP on day 7 and increases on day 14. A hypothesis concerning this biphasic change in GFAP concentrations is discussed. The results indicate that GFAP may be used to indicate the role of the astrocyte in the neurotoxicity of TMPb. GFAP concentration, as biomarker of TMPb effect, was as sensitive to TMPb as body weight and thus may provide a marker of neurotoxicity.

Animals↗

Platelet concentration and hemoglobin function in greyhounds.

Hematologic characteristics of 36 Greyhounds were studied and compared with characteristics of 22 non-Greyhound controls. Fourteen of the Greyhounds were tested and found to be seronegative for Ehrlichia canis and Babesia canis. Compared with the non-Greyhounds, Greyhounds had higher mean hemoglobin concentration, PCV, mean corpuscular volume, and mean cellular hemoglobin, and lower mean RBC count, hemoglobin P50 value, Hill coefficient, platelet count, and total plasma protein concentration. The lower mean hemoglobin P50 value in Greyhounds suggested that the higher mean hemoglobin concentration and PCV were not solely a result of selective breeding for superior racing abilities, but that Greyhound hemoglobin may have a greater affinity for oxygen than does the hemoglobin of non-Greyhounds.

Animals↗

Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma.

Five cases of dedifferentiated liposarcoma in which heterologous elements were present in the dedifferentiated component are presented. Two patients, men 54 and 66 years of age, had retroperitoneal atypical lipomatous tumors (well-differentiated liposarcomas) that recurred (after 2.5 and 12 years, respectively) as dedifferentiated liposarcomas with rhabdomyosarcomatous elements in the dedifferentiated components. The third patient, a 63-year-old woman, had a retroperitoneal dedifferentiated liposarcoma whose dedifferentiated component demonstrated focal osteoid formation. The fourth patient, a 36-year-old woman, had two seemingly separate retroperitoneal masses, one composed of atypical lipomatous tumor with foci of smooth muscle and the other of leiomyosarcoma; despite the apparent separation, it was thought more logical to consider this a dedifferentiated liposarcoma with leiomyosarcoma as the dedifferentiated component than two unrelated neoplasms. The fifth patient, a 45-year-old man, had a mediastinal dedifferentiated liposarcoma with angiosarcomatous areas in the dedifferentiated component. The relatively short follow-up thus far available on these cases has not demonstrated tumor behavior significantly different from that of dedifferentiated liposarcoma as a whole.

Adult↗

Combination chemotherapy in adult desmoid tumors.

BACKGROUND: Desmoid tumors are locally aggressive tumors, with no metastatic potential, that generally are amenable to local treatments, such as surgery and radiation therapy. Systemic therapy is considered for selected cases that are not amenable to local treatment. METHODS: The authors reviewed their experience with chemotherapy in desmoid tumors. A patient population was identified through a search of the data base maintained by the Department of Patient Studies. RESULTS: Between January 1971 and December 1991, 180 patients with a histologically confirmed diagnosis of desmoid tumor were seen at the authors' institution. Twelve patients (8 male and 4 female patients; age range, 16-66 years; median age, 29 years) received chemotherapy. Eleven patients received doxorubicin (60-90 mg/m2) plus dacarbazine (750-1000 mg/m2)-based regimens for a median of 5 cycles (2-10 cycles). Six of the nine patients who could be evaluated for response had an objective response (two complete responses and four partial responses), one patient had a minor response, and two patients had stable disease. Two other patients treated in the early 1970s could not be evaluated objectively because of lack of modern imaging; however, they were reported to have "responses" that enabled resection of axillary and pelvic disease. All four patients with Gardner syndrome experienced disease response. One of these four patients had a complete response twice with doxorubicin-based chemotherapy and eventually died with an ejection fraction of 0.22. Five patients are alive with no evidence of disease (NED), four are alive with disease, and two are lost to follow-up after having an NED status at their last visit. CONCLUSION: The authors conclude that desmoid tumors in adults are responsive to chemotherapy, and such treatment should be considered before embarking on radical treatment to avoid obvious functional consequences and delayed complications.

Adolescent↗

Durable hepatic tumor regression after arterial chemoembolization-infusion in patients with islet cell carcinoma of the pancreas metastatic to the liver.

BACKGROUND: Islet cell carcinoma of the pancreas is a neuroendocrine tumor often presenting with left upper quadrant mass and radiographic evidence of liver metastases. Because survival among these patients is determined largely by the pace of metastatic events in the liver, significant palliation may be achieved by regional hepatic therapy. METHODS: Five patients with islet cell carcinoma of the pancreas metastatic to the liver (four nonfunctional, one gastrin producing), were treated by hepatic arterial chemoembolization-infusion consisting of a mixture of polyvinyl alcohol sponge (150 mg) and cisplatin (150 mg) followed by 2-hour intraarterial infusion of vinblastine (10 mg/m2). Each patient received two such treatments, 1 month apart, requiring 3 to 6 days of hospital admission. RESULTS: Significant tumor regression (> 50%) was observed in four of five patients, lasting from 8 to 44 months. Toxicity was limited to right upper quadrant pain, paralytic ileus requiring nasogastric suction for 24 to 72 hours, transient, mild bilirubinemia and liver enzyme elevation, hypomagnesemia and hypokalemia, and occasionally, moderate, self-limiting granulocytopenia. CONCLUSIONS: This preliminary, albeit limited, experience with hepatic chemoembolization-infusion in patients with islet cell carcinoma metastatic to the liver emphasizes the high incidences of durable tumor regression that can be achieved with minimal iatrogenic intervention.

Adenoma, Islet Cell↗

Low-grade fibromyxoid sarcoma. A report of 12 cases.

Twelve cases of low-grade fibromyxoid sarcoma are presented. The patients' ages ranged from 6 to 51 years; all but three were between 26 and 46 years of age. The tumor was located in the thigh or inguinal area in four patients, in the shoulder area in three patients, and in the axilla-chest wall area, the perineum, the small bowel mesentery, the neck, and the buttock in one patient each. Tumor size (maximum dimension) varied from 3.5 to 15 cm in the nine cases in which it was known (median, 9.5 cm). Histologically, the neoplasms demonstrated contrasting fibrous and myxoid areas, a swirling, whorled growth pattern (at least in part), and bland, deceptively benign-appearing fibroblastic spindle cells; cellularity was low to moderate, mitotic figures were uncommon, and nuclear pleomorphism was usually absent or slight. Focal histologic findings in a minority of the cases included increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network (vascularity was usually not prominent). On follow-up, nine patients experienced local recurrence (from one to numerous times); recurrence was subsequently controlled in five cases but not in the remaining four. Distant metastasis occurred in seven cases, chiefly to the lungs, but two of these patients were rendered tumor-free (to latest follow-up) by excision of metastases. At latest follow-up, four patients had died of tumor at 8, 9, 31, and 31 1/2 years, respectively, three were alive with recurrent or metastatic tumor at 6 1/2, 12 1/2, and 50 years, respectively, and five were alive and tumor-free at 5 1/2, 10 1/2, 12, 22 1/2, and 44 years, respectively. One tumor, in the patient who died at 31 years, demonstrated "dedifferentiation" at 30 years. Low-grade fibromyxoid sarcoma is a distinctive, indolent soft-tissue sarcoma.

Adolescent↗

Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases.

Twenty-six cases of epithelioid sarcoma having a minimum of 5 years follow-up are presented. The patients ranged in age from 11 to 64 years; 18 were between 20 and 40 years of age. Males predominated (18:8). The most common tumor locations were the fingers (6 cases), the wrist (5 cases), and the hand (4 cases). All tumors were typical histologically, with medium-sized to large epithelioid and plump spindle cells, a predominantly nodular growth pattern, and intranodular collagen. Features seen in a minority of cases included hyalinized collagen, calcification, myxoid areas, and focal small cells. The major factor related to distant metastasis and death from tumor proved to be tumor size; all 7 patients with neoplasms > or = 5 cm died of tumor, and 6 had distant metastases, whereas only 2 of 10 patients with smaller tumors developed distant metastases and died (of patients with neoplasms of unknown size, 3 died of tumor and 2 of those along with 1 other had distant metastases). Five patients had regional lymph nodes involved (4 with tumors > or = 5 cm, 1 with tumor of unknown size), and all died. Local recurrence was primarily associated with treatment by excision alone (9 of 10 cases) rather than amputation (2 of 8 cases) or excision and radiation (2 of 8 cases); recurrences were often controlled by subsequent amputation. When tumor size and treatment were taken into account, histological variables including mitotic rate, tumor necrosis, and perineural invasion were not significantly related to recurrence, metastasis, or patient survival.

Adolescent↗