Biomedical subjects

W White

Publications and source records attributed to W White.

At least 55 records · Page 3Linked to original sources

PubMed1992

Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.

The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.

Animals↗

PubMed1992

Carvedilol in hypertension: effects on hemodynamics and 24-hour blood pressure.

Nineteen men (mean age, 44 years) with moderately severe essential hypertension were studied invasively at rest and during exercise. After initial predrug recordings, patients received 25 mg carvedilol orally, and central hemodynamics at rest and during exercise were recorded 1 and 2 h after tablet intake to evaluate the immediate effects of carvedilol. Blood pressure decreased by 11% within 1 h, and the hemodynamic results indicated a combination beta-blocking and vasodilating effect. After 6-9 months of treatment (dose, 25-100 mg), supine hemodynamics were recorded, first 12-24 h after the last dose and then 1 and 2 h after an additional 25-mg dose. During chronic treatment (2 h after the last dose with the patient at rest and in the supine position), mean arterial pressure was reduced by 17% (p less than 0.001) and total peripheral resistance index was reduced by 6% (NS), whereas heart rate and cardiac index were reduced by 12%. Exercise hemodynamics demonstrated a decrease in blood pressure of 17% (p less than 0.001). Exercise stroke index increased by 5% (NS), in part compensating for the reduction in heart rate of 17%. Total peripheral resistance index was reduced by 5% (NS). Twenty-four-hour blood pressure monitoring (Accutracker II) demonstrated significant blood pressure reductions in awake as well as in asleep patients. Blood pressures decreased from 163/102 to 141/84 mm Hg in from 135/78 to 122/68 mm Hg in awake and asleep patients; respectively. Carvedilol is an effective antihypertensive agent, and the hemodynamic mode of action reflects alpha 1- and beta 1-blocking activities.

Administration, Oral↗

PubMed1991

Intravascular ultrasound imaging for guidance of atherectomy and other plaque removal techniques.

Intravascular ultrasound imaging provides a direct view of atherosclerotic disease, generating in vivo information about the depth and mechanical characteristics of plaque at any point in the vessel wall. For this reason, ultrasound has significant potential to serve as a guidance modality for catheter-based techniques designed to remove or ablate plaque. Although the current generation mechanical atherectomy, laser ablation and ultrasound pulverization techniques all have some specificity for attacking plaque as opposed to normal vessel wall, it appears that in practice all of these devices will continue to carry a risk of traumatizing or even perforating arteries. In addition, it seems highly likely that aggressive 'debulking' of plaque will require some type of guidance beyond angiography - a role which ultrasound is theoretically well suited to play. The purpose of this review is to consider the theoretical and practical applications of ultrasound imaging as a guide to catheter-based plaque removal and ablation techniques. Specific uses will be discussed with respect to both directional and coaxial therapeutic devices.

Arteriosclerosis↗

PubMed1991

Platelet alpha 2-adrenoceptors, defined with agonist and antagonist ligands, in depressed patients, prior to and following treatment.

Saturation binding of the alpha 2-adrenoceptor antagonist, 3H-yohimbine, and displacement of 3H-yohimbine with the alpha 2-adrenoceptor agonist, UK-14,304, were performed concurrently in platelet membranes obtained from drug-free depressed patients and healthy volunteers. Where possible platelet binding was repeated in depressed patients following treatment. The number and affinity of 3H-yohimbine binding sites did not differ between controls and depressed patients, or when depressed patients were divided on the basis of endogenicity (Newcastle or RDC criteria) or dexamethasone test result. The proportion of alpha 2-adrenoceptor binding sites with high affinity for UK-14,304 and KD values for the two states of the receptor did not differ in the total sample of depressed patients compared to controls. The KD for both states of the receptor and the proportion of sites with high affinity for UK-14,304 was lower in RDC non-endogenous patients than RDC endogenous patients. Treatment did not alter the total number of alpha 2-adrenoceptors or the proportion of sites with high affinity for UK-14,304, but reduced the KD for 3H-yohimbine and the KD of UK-14,304 for the low affinity state of the alpha 2-adrenoceptor.

Adrenergic alpha-Agonists↗

PubMed1991

Interaction between Pseudomonas aeruginosa and Staphylococcus aureus: description of an anti-staphylococcal substance.

The presence of Pseudomonas aeruginosa in the sputum of 191 patients with cystic fibrosis was significantly related (p less than 0.0001) to the absence of Staphylococcus aureus. Cross-streaking tests showed that 40 of 50 clinical strains of P. aeruginosa produced substances that inhibited the growth of S. aureus. When incorporated into agar plates, this antibacterial substance(s) inhibited the growth of 177 of 189 strains of nine staphylococcal species, all of 16 methicillin-resistant S. aureus and 27 of 39 strains of six other gram-positive genera. The substance(s) did not inhibit 23 strains of seven gram-negative genera tested. The antibacterial activity was heat stable and could be extracted into chloroform; activity was retained on Sephadex G-15 (V/Vo approximately 2, Mr less than 500) and eluted as a single peak from high performance liquid chromatography, well separated from pseudomonic acid, pyocyanin and a number of other phenazines.

Anti-Bacterial Agents↗

PubMed1991

Neuroendocrine challenge studies in puerperal psychoses. Dexamethasone suppression and TRH stimulation.

Subjects admitted to hospital with post-partum psychoses were compared with matched normal post-partum controls using two neuroendocrine challenge tests: dexamethasone suppression of cortisol and TRH stimulation of TSH. Post-dexamethasone cortisol levels were significantly elevated. There were less-clear hints of blunting of TSH response. In the small samples there was no obvious association of abnormalities with any particular diagnoses within the range of mania, psychotic depression and schizoaffective disorders.

Adult↗

PubMed1991

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

Amlodipine administered once daily (5-10 mg) lowered blood pressure and reduced total peripheral resistance in patients with mild-to-severe essential hypertension without any reflex tachycardia. Heart pump function was maintained at rest and during exercise with a trend towards an increase in cardiac and stroke index. Amlodipine was effective and well tolerated in both young and elderly hypertensive patients with no reports of unpleasant vasodilator-related side effects.

Adult↗

PubMed1991

Platelet [3H]imipramine and alpha 2-adrenoceptor binding in normal subjects during desipramine administration and withdrawal.

The effect of desipramine 150 mg daily on platelet [3H]imipramine and alpha 2-adrenoceptor binding sites was studied over a 6-week period and for 6 weeks after withdrawal. Modest (10%) increases in [3H]imipramine binding site densities during treatment were noted with a decrease between 1 and 4 weeks after withdrawal. No effect was found on alpha 2-adrenoceptors. Time of day appeared to have some effect on the results found. None of the [3H]imipramine binding site effects of desipramine, on treatment or following withdrawal, was comparable in magnitude to trait differences that were also found between subjects.

Adult↗

PubMed1991

Pulmonary phaeohyphomycosis due to Xylohypha bantiana.

We encountered a rare case of pulmonary phaeohyphomycosis due to Xylohypha bantiana documented by culture. This dematiaceous (darkly pigmented) fungus is primarily neurotropic. It usually produces phaeohyphomycosis of the central nervous system but may also involve the skin and subcutaneous tissues. The patient, a 49-year-old woman with a history of steroid-treated inflammatory bowel disease, was found to have a lung nodule consisting of granulomas that contained dark hyphal fragments that stained positively with the argentaffin reaction. Surgical excision was curative and appears to be the treatment of choice.

Adrenal Cortex Hormones↗

PubMed1990

Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors.

The cellular schwannoma is a variety of schwannoma with a predominantly cellular growth but no Verocay bodies. Because doubt has been raised about the original assessment of this tumor as benign, the clinical and pathologic characteristics of 58 cellular schwannomas from 57 patients were reviewed. The patients were most often middle aged (63% were female), and their tumors most commonly were painless masses with a predilection for the paravertebral region of the retroperitoneum, pelvis, and mediastinum. Most tumors were solitary and encapsulated, and an associated nerve was identified for 43% of the cases. Electron microscopic and immunohistochemistry studies confirmed the tumor's Schwann cell nature. Worrisome features such as bone erosion, hypercellularity, foci of necrosis (four tumors), hyperchromasia, nuclear pleomorphism, and the presence of mitotic figures led to a malignant diagnosis for 28% of the cases. Treatment in all but one case was surgical excision. Two patients also received radiation therapy and chemotherapy. Follow-up of from 1 year to 24 years, 7 months (median of 6 years and mean of 7 years) for 61% (35 cases) of the cases reveals three patients with a local recurrence but no cases in which the tumor metastasized or the patient died of the tumor. Awareness of this tumor type is important so that the surgeon will avoid unnecessary sacrifice of functionally important nerves attached to these tumors and so that needless adjuvant radiation and chemotherapy will not be instituted.

Adolescent↗

PubMed1990

The futures of physicians: agency and autonomy reconsidered.

The corporatization of U.S. health care has directed cost containment efforts toward scrutinizing the clinical decisions of physicians. This stimulated a variety of new utilization management interventions, particularly in hospital and managed care settings. Recent changes in fee-for-service medicine and physicians' traditional agency relationships with patients, purchasers, and insurers are examined here. New information systems monitoring of physician ordering behavior has already begun to impact on physician autonomy and the relationship of physicians to provider organizations in both for-profit and 'not-for-profit' sectors. As managed care practice settings proliferate, serious ethical questions will be raised about agency relationships with patients. This article examines health system dynamics altering the historical agency relationship between the physician and patient and eroding the tradiational autonomy of the medical profession in the United States. The corporatization of medicine and the accompanying information systems monitoring of physician productivity is seen to account of such change, now posing serious ethical dilemmas.

Cost Control↗

PubMed1990

Keratoacanthoma necessitating metacarpal amputation.

Keratoacanthoma is usually considered a benign self-limiting lesion. First described in 1888 by Hutchinson, it most commonly involves the face and hands. It is usually controlled by complete soft tissue excision. A variant, subungual keratoacanthoma, affects bone by pressure erosion of the distal phalangeal tip. We report a case of keratoacanthoma clinically involving a metacarpal and phalanges with a radiologic and physical appearance at variance with previous reports. After multiple recurrences following erosion and cryosurgery, as well as attempted digit salvage with Mohs' surgery, ray amputation was required. The world literature pertaining to keratoacanthoma is reviewed and discussed.

Aged↗

PubMed1990

Dysfunctional attitudes and vulnerability to persistent depression.

Forty-four patients who met criteria for major depressive disorder were assessed for presence of dysfunctional attitudes and negative self-schema on admission. After six weeks, of sixteen patients who had shown high dysfunctional attitudes, six (35%) had not recovered. By contrast, of seventeen patients who had been equally severely depressed at the outset, but had low dysfunctional attitudes, only one (6%) had not recovered. The rating by the patients of themselves, as opposed to their attitudes, did not however predict. Thirty-one patients were tested six months later. Twenty-one (68%) remained asymptomatic, ten patients had relapsed or not responded to treatment, but neither type of admission measure predicted the state at this point. This is consistent with previous evidence which suggests that vulnerable attitudes assessed when symptomatic predict recovery, but that for prediction of relapse, cognitive measures need to be used when the patient is asymptomatic.

Adult↗

PubMed1990

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

The long-term haemodynamic responses to amlodipine, a new long-acting calcium antagonist, were studied both at rest and during exercise in 18 patients (mean age 43 years) with essential hypertension. Blood pressure was measured intra-arterially, cardiac output by dye dilution and heart rate by electrocardiogram. After 11 months of treatment with 5-10 mg amlodipine once daily (mean dose 9 mg/day), mean arterial pressure was reduced by 14% sitting at rest. The reduction in blood pressure was associated with a marked reduction in the total peripheral resistance index (TPRI) of 19% (P less than 0.001). Similar responses were seen supine at rest and during 50W, 100W and 150W bicycle exercise. No significant changes were seen in heart rate. There was a slight increase in stroke index, and cardiac index was preserved at rest and during exercise with a slight trend towards an increase. In 10 of the patients, blood pressure was monitored by a portable blood pressure recorder (Accutracker II, Suntech Medical instruments, Raleigh, North Carolina, USA). Blood pressure was well controlled throughout the full 24 h period after one daily dose. In conclusion, amlodipine exerts a clear antihypertensive effect, both at rest and during exercise, through reduction in the TPRI and without a fall in cardiac pump function. No changes in heart rate were seen and there was no tendency for a reduction in the stroke index during 8 min of exercise at 150 W; on the contrary there was a trend towards an increase. The incidence of side-effects was low (ankle oedema in two patients).

Amlodipine↗

PubMed1990

A superior method of tattoo removal using the Q-switched ruby laser.

The Q-switched ruby laser was used to treat 101 amateur and 62 professional tattoos in 80 patients over a period of 22 months. Using a 5- to 8-mm spot size and energy fluences of 2-4 joules/cm2, an average of three retreatments resulted in complete pigment removal in four, nearly complete pigment removal in 84, significant pigment removal in 11, and minimal pigment removal in two amateur tattoos. Using identical parameters for professional tattoos, there was complete pigment removal in two, nearly complete pigment removal in five, significant pigment removal in 18, minimal pigment removal in 25, and very little pigment removal in 12. Professional tattoos with red, yellow, and green pigments faded, but required multiple retreatments. While transient hypopigmentation occurred in many patients, skin texture and hair growth returned to normal in all cases and no hypertrophic scarring was seen.

Adolescent↗

PubMed1990

3H-imipramine binding to previously frozen platelet membranes from depressed patients, before and after treatment.

3H-imipramine binding in 39 drug-free patients with major depression and 44 healthy controls did not differ significantly between the two groups, in male or female subjects or in subgroups of depressed patients divided by endogenicity or dexamethasone suppression test result. 3H-imipramine binding in depressed patients drug-free for less than three weeks did not differ from those drug-free for longer intervals or from controls. A significant seasonal variation of 3H-imipramine Bmax was found, with lower values in summer and autumn. Treatment of depressed patients with imipramine or lofepramine for six weeks increased KD and Bmax. Methodological modification (in preparation and storage of platelets) does not explain the major differences in results between this study (using frozen platelets), a previous one (using freshly prepared platelets) and others in general, although it might contribute to the range of values reported.

Adult↗

PubMed1989

Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache.

In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using chi 2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department.

Acute Disease↗

PubMed1989

Modulation of in vitro synthesis of immunoglobulin and the induction of suppressor activity by therapy with intravenous immune globulin.

Intravenous immune globulin has become an important modality of replacement therapy for children and adults with hypogammaglobulinemia or agammaglobulinemia. It is also evident that intravenous immune globulin is effective in patients with a variety of automimmune disorders. The present study was undertaken to evaluate the effects of intravenous immune globulin replacement therapy in patients with common variable hypogammaglobulinemia. We measured pokeweed mitogen-induced immunoglobulin synthesis of patients' peripheral blood mononuclear cells cocultured in equal numbers with normal subjects' lymphocytes to assess suppressor cell activity. The mean suppressor cell activity in coculture experiments at baseline of nine patients in the study was -16%. Suppressor activity was demonstrated in two of nine patients at baseline who received intravenous immune globulin therapy before initiation of the study. After intravenous immune globulin therapy at a low dose (100 to 200 mg/kg/mo), suppressor cell activity was demonstrated in all nine patients, which ranged from -63% to -100%. In five patients intravenous immune globulin therapy was discontinued for 4 months. There was a return to baseline levels, with suppressor activity ranging from -20% to -50%. On reinstitution of high-dose intravenous immune globulin therapy (300 to 400 mg/kg/mo), all patients except one again demonstrated increased suppressor cell activity. Cell separation and recombination cell culture experiments were performed. All patients had an intrinsic B cell defect before the initiation of therapy so that the effects of intravenous immune globulin therapy on B cell function could not be assessed. Combining normal B cells with the patient's T cell-enriched fraction showed marked suppression of pokeweed mitogen-induced immune globulin synthesis. This suppression was reversible by irradiation of the T cell fraction. Removal of CD8-positive T cells by cell sorting resulted in normal immunoglobulin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Agammaglobulinemia↗