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D S Wilkinson

Publications and source records attributed to D S Wilkinson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Nuclear enlargement induced by hepatocarcinogens alters ploidy.

Treatment of rats with low doses of hepatocarcinogens is associated with a number of phenomena, including nuclear enlargement and altered nucleocytoplasmic compartmentation, which potentially reflect initiatory changes. Since a number of investigations have indicated that changes in ploidy may relate to the development of altered foci and/or hepatocellular carcinomas in liver, and since nuclear enlargement may be associated with changes in DNA content, we examined the ploidy of rat hepatocytes following essentially nontoxic low-dose carcinogen treatment. Treatments with thioacetamide, 2-acetylaminofluorene, or dimethylnitrosamine were all associated with a notable shift of nuclei from diploid to tetraploid, in the apparent absence of nuclear replication. These changes were similar in magnitude to that associated with the substantial liver regeneration induced by carbon tetrachloride. If it is argued that cell replication is a necessary prerequisite for the completion of initiation, these data suggest that there may be thresholds for initiation.

2-Acetylaminofluorene↗
PubMed1992

Dermatitis artefacta as the presenting feature of auto-erythrocyte sensitization syndrome and naproxen-induced pseudoporphyria in a single patient.

A female patient presented with two episodes of apparent dermatitis artefacta. Although it was clear that self-induced lesions were present on both occasions, there was also strong evidence in support of auto-erythrocyte sensitization syndrome on the first occasion and of naproxen-induced pseudoporphyria on the second occasion. The occurrence of two such rare disorders in a single patient is extremely unusual, and we discuss a possible pathogenetic link between them. The case emphasizes that patients with apparent artefactual lesions, or with a previous history of dermatitis artefacta, still require careful evaluation to identify organic disease.

Adolescent↗
PubMed1992

Discerning malignancy in human adrenocortical neoplasms: utility of DNA flow cytometry and immunohistochemistry.

In order to evaluate more objective laboratory methods that may help practicing pathologists to discern malignancy in human adrenocortical neoplasms, we have examined cellular DNA content by flow cytometry and immunohistochemical distribution of c-myc, vimentin, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR) in 15 cases of human adrenocortical neoplasms (nine carcinomas and six adenomas). All of these examinations were performed on routinely processed surgical pathology specimens. All carcinoma cases met Weiss's histologic criteria. Seven of eight adrenocortical carcinomas demonstrated aneuploid DNA content, while all adenomas were diploid by flow cytometry. c-myc oncoprotein was observed both in cytoplasms and nuclei in all carcinomas but only in nuclei in adenomas. Vimentin was present in all carcinoma cases examined but was also observed in three of six cases of adenoma. There were no clinical or histologic differences between vimentin-positive and vimentin-negative adenomas. Immunoreactivity of PCNA and EGFR was observed in all the cases examined. There were no significant differences in distribution or patterns of immunoreactivity between adrenocortical carcinoma and adenoma. Therefore, we conclude that only DNA ploidy examined by flow cytometry and immunolocalization patterns of c-myc oncoprotein expression have any practical value in the pathologic evaluation of adrenocortical neoplasms. Careful morphologic and/or clinical studies are still considered to be the best available methods in discerning malignancy in resected human adrenocortical neoplasms.

Adenoma↗
PubMed1991

Single-parameter DNA flow cytometric analysis of normal-appearing colonic mucosa does not predict the presence of colonic neoplasia.

We wished to determine whether DNA flow cytometric analysis could detect DNA abnormalities in normal-appearing mucosa of patients with colonic neoplasia. Eighty-five patients were studied either at colonoscopy or at surgical resection. Forty-five had macroscopically normal colonoscopy; 13 had adenomatous polyps, and 27 had colorectal carcinoma. Biopsies were obtained from the cancer and from normal-appearing mucosa 5 cm from the lesion. The patients who had normal colonoscopy had rectal biopsies. The samples were prepared for analysis on a Coulter EPICS C flow cytometer. Cells were analyzed for presence of aneuploidy (%AN), percent in DNA synthetic phase (%S), and percent growth fraction (%GF = %S + %G2M). Aneuploidy was present in 12 of 27 carcinomas (44%), but in none of the samples from polyps or normal-appearing colorectal mucosa adjacent to cancers. The %S from cancers was greater than those from polyps (9.6 +/- 6.3 vs. 5.1 +/- 1.8, p less than 0.005). However, %S from specimens arising from normal-appearing mucosa 5 cm distant from cancer could not be differentiated from the rectal mucosa of macroscopically normal colons (5.9 +/- 2.5 vs. 5.2 +/- 2.7). The %GF of cancer specimens was greater than those from adenomas (26.0 +/- 11.0 vs. 10.8 +/- 3.7, p less than 0.005). However, the %GF of normal-appearing mucosa 5 cm distant from the cancer was similar to the findings from mucosa arising from macroscopically normal colons (10.5 +/- 3.3 vs. 11.0 +/- 3.4). In conclusion, DNA flow cytometric analysis of normal-appearing colonic mucosa from patients with colonic carcinoma does not demonstrate abnormalities of DNA content or cell cycle kinetics, and therefore, cannot predict the presence of colonic neoplasia.

Adult↗
PubMed1990

Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry.

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.

Blotting, Southern↗
PubMed1990

Protooncogene amplification and tumor ploidy in human ovarian neoplasms.

DNA from 24 ovarian tumors, including 16 carcinomas, was examined for amplification of the proto-oncogenes c-myc, int-2, and rc-erbB-2. All cases of carcinoma were also examined by flow cytometry for DNA ploidy and cell cycle analysis, and eight cases of carcinoma were examined for estrogen and progesterone receptors. Protooncogene amplification was not detected in the DNA of benign ovarian neoplasms, or of ovarian carcinomas with low malignant potential. Amplification of c-myc was detected in six of 12 cases of invasive carcinoma, int-2 amplification was present in one case, and c-erbB-2 amplification was not detected in any case. Among the seven cases evidencing protooncogene amplification, three cases showed aneuploidy in tumor DNA, while four showed diploidy. Two cases which showed aneuploidy in tumor DNA did not demonstrate any degree of protooncogene amplification. Protooncogene amplification was frequently associated with morphologic nuclear anaplasia and high mitotic count. Six of the seven cases demonstrating c-myc or int-2 were of the serous type or showed some degree of serous differentiation, while none of the four cases of purely mucinous carcinoma had evidence of amplification. While the total number of cases in the study was limited, it would appear from the trend demonstrated by the data that protooncogene amplification (particularly c-myc) may be involved in the pathogenesis of aggressive common epithelial tumors of the ovary.

Adenocarcinoma, Mucinous↗
PubMed1990

Granulosa cell tumor of the ovary. Histopathologic and flow cytometric analysis with clinical correlation.

Ten granulosa cell tumors of the ovary were investigated using clinicopathologic and flow cytometric parameters. Three of the patients had recurrent or metastatic lesions 3 to 9 years after resection of the primary ovarian tumor. These three cases demonstrated diploidy in both the primary tumor and metastatic or recurrent lesions. Among the seven cases without recurrence, five had diploid DNA indexes. One case was characterized by a high degree of cytologic atypia and tetraploidy (DNA index, 1.98); this patient died of metastatic breast cancer 4 years after resection of the ovarian tumor. Another case demonstrated a high mitotic rate and exhibited aneuploidy (DNA index, 1.33); this woman was alive and well at 5 years of follow-up. In this study, no correlation was found between the recurrence rate and ploidy but, in view of the small numbers and limited follow-up, we cannot definitively analyze these prognostic factors. It does not appear feasible to predict the clinical course of granulosa cell tumors by DNA flow cytometry. However, it can be concluded that: (1) most granulosa cell tumors have diploid DNA content and (2) DNA ploidy correlates well with histologic factors, such as cellular anaplasia and high mitotic activity, which may have predictive prognostic value for granulosa cell tumors.

Adult↗
PubMed1989

Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics.

Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

Adult↗
PubMed1987

Establishing a therapeutic drug monitoring consultation service.

A formal therapeutic drug monitoring consultation service (TDMCS) will enhance the clinical benefits of drug level determinations. It can result in decreased length of stay and improved risk management posture. The successful implementation of a TDMCS requires the coordinated efforts of a multidisciplinary team that may include physicians, pharmacists, nurses, and laboratory personnel. Clinical pathologists and clinical pharmacists are particularly well qualified to direct a TDMCS. Consistent delivery of quality services requires that all procedures related to the consultation process be standardized and documented in a procedures manual. The cost of providing the service may be recovered through both direct and indirect mechanisms.

Diagnostic Services↗
PubMed1987

Urine sediment analysis by the Yellow IRIS automated urinalysis workstation.

The Yellow IRIS automated urinalysis workstation (International Remote Imaging Systems, Chatsworth, CA 91311) performs urine sediment analysis with the use of Automated Intelligent Microscopy (AIM). It ranks and counts particles based on size. A split sample study using 268 individual urine specimens was performed comparing sediment analyte detection by the Yellow IRIS with that achieved by a standard manual method. The detection ratio ("positive" specimens detected by the Yellow IRIS divided by "positive" specimens detected by the manual method) for the presence of various analytes, as well as the presence of abnormal numbers of analytes, was determined. The significance of each detection ratio was tested by calculating the McNemar's statistic, which is useful in the evaluation of nonparametric data collected by two different methods on identical specimens. Results were considered abnormal if the red blood count was greater than or equal to three per high-power field, the white blood cell count was greater than or equal to five per high-power field, or squamous epithelial cells were greater than or equal to five per high-power field. The results indicate that the Yellow IRIS enhances the detection of urinary sediment components.

Autoanalysis↗
PubMed1985

Dermatitis from repeated trauma to the skin.

A moderate degree of friction is unavoidable in everyday contact between man's skin and his environment. However, excessive friction and other forms of microtrauma can cause various dermatoses as well as lesions of hair and nails. This paper illustrates that microtraumata significantly influence many skin disorders, including those of occupational origin.

Acne Vulgaris↗
PubMed1984

[Necrolytic migratory erythema: glucagonoma syndrome. Clinical and histological aspects].

The author reviews a personal and other reported cases of necrolytic migratory erythema, a useful marker of glucagon-secreting islet cell tumours of the pancreas. The lesions extend and migrate as the centres form either a bulla or a parakeratotic crust. The eruption involves particularly the body folds, feet and thighs; evolves in waves. The tongue may be smooth and firey red. Histologically, the striking feature is an eosinophilic degeneration and death of the upper part of the epidermis. Ablation of the tumour is followed by cure of the rash but in many cases the presence of metastases makes cure impossible. The exact cause of the eruption remains unknown.

Adenoma, Islet Cell↗
PubMed1984

Lithium chloride: protective and antisecretory properties in rats.

Lithium chloride was evaluated as a potential protective agent against ethanol-induced hemorrhagic gastritis in rats. Rats received lithium chloride intragastrically (30, 60, or 90 mg/kg i.g.) or subcutaneously (3, 5, 10, 15, 20, 30, 60, or 90 mg/kg s.c.), or a placebo (H2O i.g. or 0.9% NaCl s.c.). Ninety minutes later 1 cm3 of 95% ethanol was administered intragastrically. After 30 min, the rats were killed and their stomachs were removed and visually scored for gross hemorrhagic gastritis. Lithium chloride at all doses less than 3 mg/kg significantly improved hemorrhagic gastritis when compared with the placebo. Moreover, rats treated with lithium chloride intragastrically had significantly less hemorrhagic gastritis than those treated subcutaneously even though serum lithium levels were similar. To determine if lithium's protective properties related to acid inhibition, pylorus-ligated and gastric fistula rats were studied. The median effective dose for lithium chloride was 20-30 mg/kg and the nonantisecretory dose was 3 mg/kg. No difference in hemorrhagic gastritis was noted between controls and animals receiving the nonantisecretory dose. However, at higher doses (LiCl 30, 60, and 90 mg/kg), lithium's protective properties persisted in spite of adding 150 mM HCl to the intragastrically administered ethanol (p less than 0.001). To determine further if lithium chloride stimulated endogenous prostaglandins, indomethacin, a prostaglandin inhibitor, was administered. Indomethacin did not alter lithium chloride's protective properties. In fact, when compared with exogenously administered 16,16-dimethyl prostaglandin E2 (5 and 500 micrograms/kg), high-dose LiCl (30, 60, or 90 mg/kg) resulted in significantly more protection against ethanol-induced injury (p less than 0.001). In contrast, when both nonantisecretory doses were compared, 16,16-dimethyl prostaglandin E2 (5 micrograms/kg) gave significantly better protection than LiCl (3 mg/kg). These data indicate that LiCl is a potent gastric antisecretory and protective agent. The protective properties of LiCl appear to be related to acid inhibition and be independent of endogenous prostaglandins, although other protective mechanisms may be present at higher LiCl doses. Additionally, this study indicates that LiCl may have clinical application in protecting the gastric mucosa against hemorrhagic gastritis.

Animals↗
PubMed1981

Lanolin of reduced sensitizing potential.

Confirmation has been obtained that reducing the content of natural free alcohols in lanolin to below 3%, particularly in the absence of detergent residues, reduces the incidence of positive patch test reactions amongst selected lanolin-sensitive skin patients by 99.3%. Only one reaction out of 149 subjects was recorded.

Alcohols↗