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Biomedical subjects

W L Williams

Publications and source records attributed to W L Williams.

158 records · Page 9Linked to original sources

Fine needle biopsy without syringe aspiration.

Aspiration biopsies of fresh disease-free bovine hepatic liver were performed with three commercially available, small-gauge biopsy needles. A syringe was used to create a negative pressure when using Chiba and Sure-cut needles. A syringe was not used when using PercuCut needles which create an internal negative pressure equivalent to a 1.5 ml syringe when the stylet is partially withdrawn. The PercuCut and Chiba needle yielded a significantly larger specimen size than the Sure-Cut needle. There was no significant difference in sample size between the PercuCut and Chiba needles. All samples were of diagnostic quality.

Animals↗

Beyond palliative mastectomy in inflammatory breast cancer--a reassessment of margin status.

BACKGROUND: Inflammatory breast cancer is a locally advanced tumor with an aggressive local and systemic course. Treatment of this disease has been evolving over the last several decades. The aim of this study was to assess whether current therapies, both surgical and chemotherapeutic, are providing better local control (LC) and overall survival (OS). We also attempted to identify clinical and pathologic factors that may be associated with improved OS, disease-free survival (DFS), and LC. METHODS: A 25-year retrospective review performed at the City of Hope National Medical Center identified 90 patients with the diagnosis of inflammatory breast cancer. RESULTS: Of the 90 patients identified with inflammatory breast cancer, 33 received neoadjuvant therapy (NEO) consisting of chemotherapy followed by surgery with radiation (n = 26) and without radiation (n = 7). Fifty-seven patients received other therapies (nonNEO). Treatments received by the nonNEO group consisted of chemotherapy, radiation, mastectomy, adrenalectomy, and oophorectomy, alone or in combination. The median follow-up was 28.9 months for the NEO group and 17.6 months for the nonNEO group. Borderline significant differences in the OS distributions between the two groups were found (P = .10), with 3- and 5-year OS for the NEO group of 40.0% and 29.9% and for the nonNEO group of 24.7% and 16.5%, respectively. DFS and LC were comparable in the two groups. Lower stage was associated with an improved OS (P < .05). The 5-year OS for stage IIIB was 30.9%, compared to 7.8% for stage IV. In those patients with stage III disease who were treated with mastectomy and rendered free of disease, margin status was identified by univariate analysis to be a prognostic indicator for OS (P < .05). The 3-year OS, DFS, and LC for patients with negative margins were 47.4%, 37.5%, and 60.3%, respectively, compared to 0%, 16.7%, and 31.3% in patients with positive margins. CONCLUSIONS: This study suggests that in patients with inflammatory breast cancer and nonmetastatic disease, an aggressive surgical approach may be justified with the goal of a negative surgical margin. Achievement of this local control is associated with a better overall outcome for this subset of patients. The ability to obtain negative margins may further identify a group of patients with a less aggressive tumor biology that may be more responsive to other modalities of therapy.

Adult↗

Extraction of human and rabbit acrosomes: a comparison of sequential and sonication methods.

Two methods for the extraction of acrosomal membranes and enzymes from both human and rabbit spermatozoa were compared. Treatment of spermatozoa with hypotonic MgCl2 (0.05 M) solution causes removal of the plasma membrane, vesiculation, disruption and removal of the outer acrosomal membrane posterior to the equatorial segment with accompanying loss of soluble acrosomal material. Subsequent exposure to Hyamine 2389 and Triton X-100 removes acrosomal material bound to the inner acrosomal membrane with concomitant solubilization of this membrane. The MgCl2 extract from rabbit spermatozoa contained a higher yield of hyaluronidase, acrosin, and total proteinase activities, whereas the subsequent detergent extracts contained higher yields of both arylsulfatase A and B activities. By comparison, after 4 minutes of sonication to separate heads and tails, both rabbit and human spermatozoa when viewed by transmission electron microscopy showed alterations of plasma and outer acrosomal membranes with considerable loss of the acrosomal contents. Analysis of acrosomal enzymes indicates the greatest percentage of all the enzymes assayed was located in the extract obtained by sonication in contrast to either the separated head or tail fractions used for further subcellular extraction. Subsequent treatment with Hyamine and Triton yields only minimal amounts of enzyme activity.

Acrosin↗

Fine needle aspiration diagnosis of lymphomatoid granulomatosis. A case report.

The diagnosis of lymphomatoid granulomatosis (LG) of the lung depends on obtaining adequate histologic material to demonstrate the characteristic angioinvasive, polymorphous, lymphoid infiltrate and normally requires an open lung biopsy. Fine needle aspiration biopsy (FNAB), if only smeared directly, does not allow an assessment of the lymphoid infiltrate in relation to blood vessels. However, we report a case diagnosed by FNAB in which the specimen was processed by an alternative method that allows cell blocks to be made from all visible particles. Percutaneous FNAB of a nodular pulmonary infiltrate was performed after bronchoscopy and transbronchial needle biopsy failed to yield a diagnosis. The FNAB specimen was placed in 50% alcohol and submitted for processing. The specimen was then filtered through a fine sieve, and all visible tissue was embedded in bacteriologic agar and processed as a standard surgical specimen. The filtrate was processed as standard fluid cytology. The atypical, angioinvasive, lymphoid infiltrate was clearly demonstrated on the cell blocks, and the diagnosis of LG was made. This diagnosis was confirmed by subsequent open lung and skin biopsies.

Aged↗

Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia cells in culture by sesquiterpene lactones.

Helenalin and bis (helenalinyl) malonate, sesquiterpene lactones, were shown to be cytotoxic against the growth of P-388 lymphocytic leukemia cells in culture. DNA and protein synthesis were reduced by these agents preferentially, with RNA synthesis being affected only marginally. This study focused on the identification of the enzyme target(s) responsible for the inhibition of DNA synthesis by the sesquiterpene lactones. Purine synthesis was strongly inhibited at the IMP dehydrogenase step. Suppression of IMP dehydrogenase activity and purine synthesis paralleled the DNA synthesis inhibition with respect to both dose dependence and time of incubation with drug. Deoxyribonucleoside triphosphate pools in the P-388 cells were significantly reduced by both drugs and the DNA polymerase alpha activity was only moderately inhibited by both drugs in cytoplasmic preparation. However, inhibition of a partially purified DNA polymerase alpha was of a much greater magnitude. Activity of the ribonucleotide reductase complex was reduced by more than 50% at 100 microM concentration of either drug. The drugs appeared to affect the hydrogen donor system of the reductase complex, since the activity of the ribonucleotide reductase enzyme itself was not affected but both thioredoxin and glutaredoxin were markedly inactivated by the sesquiterpene lactones. Thymidylate synthetase activity was not affected by the sesquiterpene lactones in P-388 cells. These data suggest that the inhibition of IMP dehydrogenase and the ribonucleotide reductase complex activities by helenalin and bis (helenalinyl) melonate was the primary reason for the observed inhibition of DNA synthesis, but that inhibition of DNA polymerase alpha may also play a role. The inhibition of the sensitive enzymes is likely to be related to drug alkylation of thiol active groups of the enzymes in a manner similar to the action of N-ethylmaleimide. The mode of action of helenalin and bis (helenalinyl) malonate does not appear to be similar to that of the parthenolide-type sesquiterpene lactones which contain an epoxide moiety.

Animals↗

Local morphologic effects of coronary artery balloon angioplasty.

The morphologic effects of percutaneous transluminal coronary artery balloon angioplasty (PTCA) on atherosclerotic vessels is described in six patients who died at varying intervals after the procedure (four early and two late). In the early group (less than one week post PTCA) one patient died because of electromechanical dissociation during emergency PTCA for evolving infarct; in the three other patients PTCA was performed for left main occlusion and cardiogenic shock with deaths 3, 24 and 25 h after PTCA. The two late deaths were patients who died one and nine months after PTCA from unrelated causes. There were 12 sites of balloon inflation in the six patients, all in left main, isolated marginal or left anterior descending arteries. Post mortem examinations, with in toto serial sectioning of the ballooned coronary arteries, revealed a number of local morphologic changes. Plaque fractures and disruptions of the arterial wall to variable depths were observed. At four sites these fractures were through media, and at one site was associated with a large dissection. These cases had only small epicardial hemorrhages or reactive adventitial changes associated with these deep fractures. Four of the six patients had intramural arterial emboli (athero/thrombo/calcium/foreign body). These findings confirm that a large part of the effect of PTCA is due to physical disruption of plaque and underlying native vessel.

Adult↗

Processing of aspiration cytology samples. An alternative method.

Cytotechnologists usually assist in smear preparation during radiologic fine needle aspiration (FNA) procedures. An alternative technique is presented that requires neither cytotechnologist participation nor immediate processing. In 111 consecutive patients undergoing FNA procedures, the aspirate was immediately fixed in 50% ethanol. The specimen was refrigerated and later processed in the laboratory as cell block preparations, which often maintained the original histologic architecture, and smears, which demonstrated good nuclear detail without air-drying artifacts. In our patients, this technique was 95% sensitive and 100% specific for the diagnosis of malignancy.

Biopsy, Needle↗

Acute toxicity of aflatoxin B1 and rubratoxin B in dogs.

The effect of ip administrated aflatoxin B1 and rubratoxin B, singly and in combination, on dogs was determined by serum tests, by observations of clinical signs and survival times, and by evaluation of gross and microscopic lesions. The dog is sensitive to the toxic effects of both mycotoxins. Glutamic-oxaloacetic transaminase, lactic dehydrogenase and alkaline phosphatase activities and survival time varied in relation to dose and to the mycotoxin(s) administered. All three plasma enzymes were elevated regardless of dose with the combination of aflatoxin B1/rubratoxin B at 24 hr after dosing, except LDH, which was within the normal range but only at the lowest dose level. Several serum constituents including BUN, cholesterol, uric acid, and total bilirubin were elevated, whereas serum glucose was depressed in dogs treated with the multiple-toxin regimen; these changes were not seen in dogs given only aflatoxin B1 but were characteristic in rubratoxin-treated animals. In general, gross findings at necropsy were similar in all dogs regardless of the dose regimen. A striking similarity existed in the histologic changes observed between lesions experimentally induced by the mycotoxin combination and those lesions reported for dogs fed toxic feed in laboratory studies or in natural cases of hepatitis X. Of particular similarity were the severe kidney lesions observed in dogs exposed to the mycotoxin combination and kidney lesions reported in natural outbreaks of hepatitis X. There can be little doubt of an association between hepatitis X and aflatoxin B1, although it is apparent that the disease probably involves more than a single toxic factor. Our results suggest that hepatitis X in dogs includes aflatoxin B1 as a primary etiological factor but that rubratoxin B also may be involved.

Aflatoxins↗