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Biomedical subjects

W C Clark

Publications and source records attributed to W C Clark.

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

Clonal composition of glioblastoma multiforme.

Glioblastoma multiforme, the most common and most lethal primary central nervous system neoplasm, is noted for its phenotypic and biological heterogeneity. This heterogeneity may result from genetic alterations accumulated by a single transformed astrocyte as it evolves into a monoclonal tumor. Alternatively, it may be attributed to the presence of multiple biologically and genetically distinct astrocytic populations within a polyclonal tumor. To address the issue of clonal composition of glioblastoma multiforme the authors used two independent approaches: analysis of X-chromosome inactivation and analysis of chromosomes 10 and 17 for tumor-specific somatic deletions. The analysis included 10 tumors from nine female patients with glioblastoma multiforme (eight primary and two recurrent tumors), who were heterozygous at either of two X-chromosome genes (hypoxanthine phosphoribosyl-transferase or phosphoglycerate kinase). Nine glioblastomas multiforme demonstrated a monoclonal pattern on X-chromosome analysis; contamination with normal tissue obscured the analysis in one tumor. Somatic deletions on chromosomes 10 and/or 17 occurred in nine tumors, supporting a monoclonal composition for these tumors. These data suggest that glioblastoma multiforme is a monoclonal neoplasm, derived from the clonal expansion of a single transformed astrocyte that has, as a fundamental step in tumorigenesis, sustained a critical genetic alteration on chromosome 10 and/or 17.

Brain Neoplasms↗
PubMed1992

Disorders of cerebrospinal fluid circulation and edema.

An assessment of contemporary techniques for the diagnosis and management of hydrocephalus and brain edema are reviewed. Further refinements in magnetic resonance imaging (MRI) techniques may aid in the selection of patients with normal pressure hydrocephalus (NPH) who respond to shunting.

Brain Edema↗
PubMed1991

Sensory decision theory and visual analogue scale indices predict status of chronic pain patients six months later.

Thirty-nine outpatients suffering from chronic pain were studied in a multidisciplinary program. Pain intensity on a visual analogue pain scale (VAPS), sensory decision indices of thermal discriminability, P(A), and pain report criterion, B, age and sex obtained before treatment, were used to predict the patients' status, determined by a follow-up questionnaire 6 mo later. The results showed that patients who were high on the VAPS at intake had shorter pain relief and decreased physical activities on follow-up. Patients with better thermal discriminability had greater pain relief, while those with low pain report criterion, that is, less stoical, demonstrated improved physical activity, and more social and hobby activities. Patients who were less stoical to thermal stimuli (lower pain criterion) took fewer centrally active drugs after treatment. Younger patients showed greater improvement at follow-up. The data indicate that the VAPS, thermal discriminability, and pain report criterion all predict the duration of pain relief after treatment. Nevertheless, each of these variables had its individual character. The VAPS was most efficient in predicting physical activities, thermal discriminability related best to pain relief, and pain report criterion to social and hobby activities as well as drug intake.

Adult↗
PubMed1991

Immunocytochemical evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis.

Neoplastic angioendotheliomatosis is a rare disorder usually characterized by primarily cutaneous or neurological symptoms. Approximately 40 cases of malignant angioendotheliomatosis with primary central nervous system (CNS) symptoms have been reported. Some investigators have postulated a hematopoietic origin for this neoplasm. Most of the literature, however, has perpetuated the idea that the often bizarre symptoms seen with this entity result from neoplastic endothelial cell proliferation within the small vessels of affected organs, including the brain and spinal cord. This report describes the immunohistochemical examination and confirmation of the cell of origin of this neoplasm based on five previously unpublished cases of malignant angioendotheliomatosis with primarily CNS symptoms. It includes the first documentation of a T-cell lymphoma presenting as malignant angioendotheliomatosis. All cases include autopsy findings, and in four cases the diagnosis was made postmortem. One case was proven by stereotactic biopsy, but the patient succumbed as a result of severe intracranial bleeding that occurred at the time of biopsy. Tissues were studied with avidin-biotin peroxidase immunohistochemical techniques using a panel of monoclonal antibodies directed against the leukocyte common antigen, LN-1, LN-2, and anti-Factor VIII, and also using Ulex europaeus agglutinin 1. Based on the results obtained, the authors conclude that the proliferative cells seen within the vessel lumina are of lymphocytic origin and agree that the condition should more properly be designated intravascular lymphomatosis. The therapeutic implications of this conclusion point to the possible administration of chemotherapy and radiotherapy in an effort to achieve remissions in an otherwise relentlessly progressive neurological disorder.

Adult↗
PubMed1991

Multidimensional scaling of painful and innocuous electrocutaneous stimuli: reliability and individual differences.

Multidimensional scaling was used to explore whether a single intensity dimension underlies the perception of both nonpainful and painful electrical stimuli, or whether separate dimensions are required. For the scaling (INDSCAL) procedure, 41 healthy volunteers judged the similarity between all pairs of 16 intensities, which ranged from imperceptible levels to pain tolerance. For the property mapping (PREFMAP) analysis, they rated each intensity on each of 16 property scales. INDSCAL revealed four dimensions that showed high levels of both test-retest and split-half reliability. The first dimension scaled stimuli from the lowest intensity to the pain threshold. This dimension was related to property scales of sensation, affect, and arousal, but not pain, suggesting a sensory magnitude dimension. The second dimension ordered the stimuli from mildly to severely painful and was related to the painful property scale, suggesting a pain intensity dimension. Third and fourth dimensions, which refined the scaling of nonpainful stimuli, were also found. Variability in the subjects' use of the painful and nonpainful dimensions was related to their choice of stimulus descriptors. Like clinical pain, laboratory pain requires multidimensional assessment.

Adolescent↗
PubMed1990

Multidimensional scaling of subjective judgements of drug similarities among ketocyclazocine, morphine, cyclazocine, naloxone and placebo.

Profiles of the subjective and physiologic effects of opioid drugs in man cannot be assigned with precision to specific opioid drug-receptor interactions. We administered a set of training doses of ketocyclazocine, morphine, cyclazocine, naloxone and placebo to 10 drug-using volunteers and obtained similarity judgements between each of 2 test doses of the drugs and a training dose. These data were submitted to multidimensional scaling analysis (INDSCAL) using both neighboring cells estimates and root mean square estimates to estimate missing cells in the data matrices. The results of these analyses are convergent, appear valid and indicate that there are three drug dimensions expressed in this data set: morphine versus placebo and naloxone; cyclazocine and ketocyclazocine versus placebo and naloxone; and ketocyclazocine versus cyclazocine. We interpret this result as supporting evidence that in the set of five drugs studied, three subjective states are induced.

Adult↗
PubMed1989

Complications of intracranial pressure monitoring in trauma patients.

A retrospective review of 175 intracranial pressure (ICP) monitors placed in 140 trauma patients over a recent 3-year period showed a 10.3% infection rate. Factors that were related to the development of an ICP monitor-related infection included: 1) duration of monitoring; 2) requirement for serial monitors; and 3) concurrent infection at other sites. These findings are discussed in light of the related literature concerning ICP monitoring and recommendations made to decrease the incidence of infection-related complications.

Adult↗
PubMed1989

Monoclonal antibody immunophenotyping of solitary cerebral metastases with unknown primary sites.

Various authors have reported the incidence of the solitary metastatic lesion to range from 25-85% of cases with known cerebral metastasis. In about 20% of these cases, no primary neoplasm is ever identified. The therapeutic alternatives considered depend to a great extent on the histopathology of the tumour. Unfortunately, the difficulty of making a correct diagnosis in this setting is compounded by all of the problems associated with tumour sampling, i.e. the representativeness of the sample, the often miniscule amounts of tissue obtained, mechanical deformation of the sample, etc. This study describes the use of a monoclonal antibody panel in the immunophenotyping of 45 tumours where the differential diagnosis was glioma versus metastatic tumour with no known primary site. The monoclonal antibodies used bound neuroectodermal antigens (UJ13A), cytokeratin (LE61), and epithelial membrane antigens (AUA1), as well as human milk fat globule antigens (HMFG1, HMFG2). The neuroectodermally-derived MAB UJ13A accurately and reproducibly differentiated gliomas and metastatic lesions with one exception. Oat cell carcinomas (n = 5) were positive for both UJ13A and cytokeratin (LE61). There were no cases in which metastatic tumours were positive for UJ13A and negative for cytokeratin. A combination of the LE61 and AUA1 MABs resulted in positive staining in 44/45 (98%) cases. Immunophenotyping made a substantial contribution in 13 cases (29%), and in three cases the MAB panel was responsible for the final diagnosis. The antibody panel described in this study enables primary CNS neoplasms to be accurately distinguished from nonlymphoid metastatic tumours. In addition, a positive diagnosis of carcinoma is made in 98% cases, although identification of the precise organ of origin is not generally possible.

Adenocarcinoma↗
PubMed1989

Primary optic nerve sheath meningiomas. Report of nine cases.

Between 1979 and 1987 the authors treated nine cases of primary optic nerve sheath meningioma. The definitive treatment for these lesions is surgical resection, although no single best plan for optimal management has been determined. The data indicate that only small anterior tumors may be removed with preservation of useful vision. With posterior circumferential tumors, there have been no cases of tumor removal with preservation of vision. A management strategy directed toward preservation of vision is discussed.

Cranial Nerve Neoplasms↗
PubMed1988

Transforming growth factor-beta-like activity in tumors of the central nervous system.

Transforming growth factor type beta (TGF-beta) is a ubiquitous peptide with wide-ranging regulatory functions. This paper reports the initial isolation of TGF-beta activity from human glial and mesenchymally derived tumors and a human glial tumor cell line. While its physiological function at the molecular level is not yet defined, it is believed that this peptide plays a central role in the control of growth and transformation, with the exact role it plays being a function of the entire set of growth factors present in a given cell.

Animals↗
PubMed1988

Infection-related spontaneous atlantoaxial dislocation in an adult. Case report.

This paper reports the third described case of infection-related atlantoaxial subluxation in an adult. Like most of the similar cases seen in the pediatric literature, this case was associated with a parapharyngeal beta-hemolytic streptococcal abscess. Based upon this experience, the authors advocate intravenous antibiotic therapy and 1) immediate reduction followed by application of a halo brace; 2) immobilization in a halo brace for at least 3 months; and 3) a C1-2 wiring and fusion procedure for patients who fail this trial of conservative therapy.

Abscess↗
PubMed1987

Reduced systemic drug exposure by combining intraarterial cis-diamminedichloroplatinum(II) with hemodialysis of regional venous drainage.

During cancer chemotherapy toxicity to normal tissues often limits the tolerable dose. To increase drug delivery to tumor while maintaining tolerable systemic exposure, regional treatments, such as intraarterial drug delivery, have been used. Despite intraarterial delivery, systemic toxicity often remains the dose-limiting sensitivity. If systemic drug exposure could be reduced after intraarterial infusion, the intraarterial dose could be increased, which should increase the therapeutic response. We compared the pharmacokinetic advantage after cisplatin infusion into the internal carotid artery to that obtained after infusing cisplatin into the internal carotid artery during extracorporeal removal of cisplatin from the jugular blood by hemodialysis. Four patients with malignant gliomas received intracarotid cisplatin, 100 mg/m2 over 60 min, every 4 weeks. During one treatment, while cisplatin was infused into the internal carotid artery, the jugular blood was dialyzed extracorporeally at 300 ml/min and returned to the inferior vena cava. Seventy to 96% of the free platinum that entered the dialyzer was removed. By aspirating blood from the jugular vein at 300 ml/min, 30-79% of the ipsilateral carotid blood was collected for extracorporeal circulation. Hemodialysis of the cerebral venous drainage during intracarotid infusion reduced the systemic exposure to cisplatin by 51-61% when compared to the exposure from internal carotid artery infusion without hemodialysis. The pharmacokinetic advantage (brain/body exposure ratio) was increased from 3 to 5/1 during internal carotid artery infusion alone to as much as 15/1 during treatment combining intracarotid infusion with hemodialysis of the jugular blood. Systemic toxicity now limits the dose of cisplatin that can be administered safely. Increased tumor exposure without increased systemic toxicity may be possible with the technique described and greater doses of cisplatin. Assuming no associated local toxicities, the results of the current study indicate that the dose of intracarotid cisplatin can be increased while maintaining tolerable systemic exposure.

Brain Neoplasms↗
PubMed1986

Differential responses of the dopa decarboxylase gene to 20-OH-ecdysone in Drosophila melanogaster.

The dopa decarboxylase gene (Ddc) of Drosophila melanogaster responds to 20-OH-ecdysone in the mature larval epidermis and in imaginal discs (presumptive adult epidermis) in a tissue-specific manner. Exposure of the mature larval epidermis to 20-OH-ecdysone caused a rapid accumulation of DDC transcripts. In the absence of protein synthesis, transcript accumulation was substantially reduced suggesting an indirect hormonal effect on DDC transcription (and/or RNA turnover). By contrast, neither DDC activity induction nor transcript accumulation was detected in imaginal discs cultured in the continuous presence of the hormone. However, when discs were exposed to 20-OH-ecdysone and then cultured in its absence, DDC activity and DDC transcript levels started to increase 6 hr after hormone withdrawal. A Northern analysis failed to reveal any novel transcripts in discs making the utilization of an alternative promotor an unlikely explanation for the very different responses of the Ddc gene in the two epidermal tissues. The results demonstrate that the Ddc gene in the larval epidermis responds rapidly to an increase in hormone titer. In imaginal discs a fall in hormone titer is required before DDC transcripts accumulate.

Animals↗
PubMed1986

Multidimensional scaling reveals two dimensions of thermal pain.

The Individual Differences Scaling (INDSCAL) model of multidimensional scaling was used to explore the dimensions of thermal pain. The observers made 66 similarity judgments to all pairs of 12 different thermal stimulus intensities ranging from zero to noxious. Analysis of the data revealed a two-dimensional group stimulus space. The major dimension ordered the stimuli with respect to their intensity. This quantitative, strength-of-sensation dimension may be interpreted as indicating how weak or strong a stimulus feels, apart from any secondary qualities of warmth or pain. The second dimension was related to the qualitative aspects of the stimuli. This bipolar dimension contained two attributes: a pain attribute ranging from just detectable warmth to painful, and a warm-hot attribute running from just detectable warmth to hot. This study demonstrates the utility of the INDSCAL approach to the understanding of pain and offers a new technique for answering the age-old question concerning the number and qualities of the dimensions underlying the pain experience.

Adult↗
PubMed1986

Altered pain and visual sensitivity in humans: the effects of acute and chronic stress.

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Acupuncture Therapy↗