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Biomedical subjects

T King

Publications and source records attributed to T King.

At least 19 recordsLinked to original sources
PubMed1995

Bidirectional activity of 11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle cells.

Endogenous glucocorticoids (GC) can be metabolized through the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD); in the rat, corticosterone (B) is converted to its inactive metabolite 11-dehydrocorticosterone (A). Since increased tissue concentrations of GCs may affect blood pressure by potentiating the vasoactive effects of alpha-adrenergic agonists and possibly other pressors, we studied the metabolism of corticosterone in freshly dissected aortae and cultured vascular smooth muscle cells (VSMC). Incubations were generally conducted for 60 min with 10(-8) M steroid; steroids were isolated and identified by HPLC. In aortic minces stripped of endothelium, the oxo-reductase reaction of A back to B was nearly 4 times greater than the dehydrogenase reaction of B to A (2.8 +/- 0.5 x 10(-11) versus 7.3 +/- 1.0 x 10(-12) mol/mg protein). This pattern was also seen in cultured VSMC during growth and quiescent states (growth A to B 3.2 +/- 0.4 x 10(-12) versus B to A 9.7 +/- 0.9 x 10(-13) mol/mg protein; quiescent A to B 8.8 +/- 0.1 x 10(-12) versus B to A 1.2 +/- 0.2 x 10(-12) mol/mg protein). Enzyme activity in either direction was less during growth, correlating with a decrease in mRNA for 11 beta-OHSD. In cell homogenates containing 200 microM NADP(H), the enzyme functioned equally in either direction at pH 7.4 with an apparent Km for corticosterone of approximately 2 x 10(-7) M. Carbenoxolone, an inhibitor of 11 beta-OHSD, suppressed the dehydrogenase reaction to a greater degree than the reverse oxo-reductase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.

The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.

Adult↗
PubMed1992

Colonic mucosal mast cell distribution at line of demarcation of active ulcerative colitis.

We examined the distribution of colonic mucosal mast cells in 25 patients with active ulcerative colitis, with a clear line of demarcation separating active inflammation from normal mucosa. Biopsies, at least one adjacent to the line of demarcation, one in inflamed mucosa, and one above were obtained during colonoscopy. Eight patients had elevated mast cells throughout the colon, and 12 had increased numbers at the line of demarcation of disease. Mean numbers of mast cells from these patients were 6.3 (+/- 2.1 SD) in active inflammation, 19.5 (+/- 7.1 SD) at the line of demarcation, and 15.8 (+/- 8.4 SD) in normal mucosa. Histologic inflammation decreased as mast cells increased. The accumulation of mast cells at the visible line of demarcation between normal and abnormal mucosa suggests mast cells play a critical role in either accelerating the process of inflammation or in suppressing continued extension of the disease.

Adult↗
PubMed1992

Lower-extremity amputation with immediate postoperative prosthetic placement.

To study the efficacy of an immediate postoperative prosthesis (IPOP) program, a retrospective review of 167 major lower-extremity amputations was performed. Patient enrollment in the IPOP program was based on the individual's potential for rehabilitation and participation in an aggressive postoperative physical therapy regimen, as determined by the surgeon, prosthetist, physical therapist, and social worker. Indications for amputation were intractable infection and/or severe unreconstructable arterial insufficiency. Sixty-five patients underwent 69 amputations with IPOP (59 below knee; 10 above knee). Successful program completion was defined as independent ambulation and occurred in 86% of those patients enrolled. The average interval from amputation to ambulation was 15.2 days for the below-knee amputees and 9.3 days for the above-knee amputees. Failure to complete the program occurred in 14% of patients and was due to noncompliance, stump infection, stump trauma, and death. The results of this review support the use of IPOP after major lower-extremity amputation.

Adult↗
PubMed1992

Reversible vasospasm in association with the use of heparin and dihydroergotamine.

A case of reversible vasospasm is reported in a 54-year-old man with a closed bimalleolar ankle fracture. On admission the patient had normal distal pulses and laboratory studies. He was a heavy smoker who continued to smoke in the hospital. Deep venous thrombosis (DVT) prophylaxis included dihydroergotamine and heparin (DHE-H). In the early postoperative period, marked spasm of all three arteries developed on the operative side. Smoking privileges and DHE-H were discontinued. The vasospasm resolved after intraarterial nitroglycerin. This case suggests an infrequent but potentially limb-threatening complication of DHE-H.

Ankle Injuries↗
PubMed1991

Outcome of complex vascular and orthopedic injuries of the lower extremity.

Thirty-two patients undergoing limb salvage procedures for complex vascular and orthopedic injuries of the lower extremity were studied in order to identify prognostic indicators for delayed amputation in this select group. A high incidence of nerve (38%), soft tissue (66%), and remote injury (47%) was noted. A comprehensive and integrated approach to vascular, orthopedic, and plastic reconstruction was utilized. Of the 32 patients studied, 1 (3.1%) died as a result of remote injury and sepsis. Amputation was required in 9 patients (28%), while 13 (56%) of the patients with limb salvage showed persistent functional or neurologic deficits. Infection was the most significant factor associated with amputation (p less than 0.0005) and was not avoided by the perioperative use of antibiotics. Delayed amputation resulted in a significant extension of total hospitalization (p less than 0.005). The authors favor an aggressive approach to limb salvage with IIIC injury but recommend early amputation in the presence of significant nerve disruption. An attentive use of tissue debridement, intravenous antibiotics, and early wound coverage is needed to limit infection.

Adolescent↗
PubMed1991

Brachial plexus palsy with the use of haloperidol and a geriatric chair.

An 81-year-old white man was admitted to an intermediate care facility because of increased wandering and confusion secondary to dementia. On the first day after admission, the patient tried to leave the facility and was hitting and kicking the employees. Haloperidol 0.5 mg tid was prescribed to help control his behavior. He became more agitated and confused; haloperidol was then increased to 1 mg qid and the patient was confined to a geriatric chair to prevent injuries. Cogwheel movements, rigidity, and marked sedation were documented. A right brachial plexus palsy was diagnosed. This case demonstrated the hazards of two commonly used interventions in a nursing home: antipsychotic agents and the geriatric chair.

Aged↗
PubMed1991

Maternal clofibrate administration amplifies fetal peroxisomes.

To study the effects of peroxisome proliferators on fetal biogenesis, 400 mg/kg oral clofibrate was administered to pregnant mice beginning at d 6 of gestation. Maternal/fetal tissues from three separate experiments were harvested between gestational d 13 and 19 and maternal/fetal tissues were assayed for peroxisomal matrix, membrane-associated, and integral membrane proteins. By comparison to control pregnancies that received vehicle only, clofibrate produced a 4- to 5-fold increase in the levels of peroxisomal membrane protein 70, a 1.5- to 2-fold increase of dihydroxyacetone phosphate acyltransferase (DHAP-AT) sp act, and a 1.2- to 1.8-fold increase of catalase sp act in fetal liver of 19 d gestation. Fetal liver endoplasmic reticulum and peroxisomes were also amplified as visualized by electron microscopy. Clofibrate exhibited maximal effects on maternal tissues by 6 d of oral treatment with increases in peroxisomal membrane protein 70 occurring most clearly in maternal liver; DHAP-AT activity was increased in maternal liver, kidney, and brain but not in lung. Slight increases in DHAP-AT activities were evident in fetal brain, lung, and placenta as compared with the greater increases in liver and kidney. There was a general increase in peroxisomal proteins between 13 and 19 gestational d in all fetal tissues except placenta, and the effect of clofibrate was evident by gestational d 13 in lung and placenta. Minimal changes in the activities of acid phosphatase (lysosomal enzyme) or glycerol-3-phosphate acyltransferase (microsomal enzyme) were observed in maternal or fetal tissues although the latter enzyme was increased 10-30% by clofibrate in maternal brain, fetal lung, and placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗
PubMed1990

Evaluation of the need for follow-up in an out-patient clinic.

We have identified 164 patients regularly attending a chest clinic whose condition had been defined as stable on the basis of clear-cut criteria. These patients were randomly allocated to either routine follow-up at 3 monthly intervals (the 'follow-up' group) or annual follow-up (the 'discharge' group). After 1 year, on the basis of a questionnaire sent to the patients' general practitioners, there were no significant differences in outcome between the two groups apart from a just-significant increase in deaths in the 'follow-up' group. Nevertheless, at the conclusion of the trial clinic doctors felt that only 45% of patients and general practitioners that only 27% of patients should be discharged from the clinic. At the conclusion of the study patients in the 'discharge' group were significantly more likely to feel that they had been attending too infrequently and that their condition had worsened, although the latter was not borne out by objective data. We suggest that all these patients could have been discharged from the clinic without any difference in outcome. This study highlights the reluctance of clinic doctors and general practitioners to consider and effect the discharge of stable patients from routine clinic attendance.

Ambulatory Care Facilities↗
PubMed1989

Human rhabdosarcoma cell-induced aggregation of blood platelets.

The ability of tumor cells shed into the circulation to cause adhesion and aggregation of blood platelets may be involved in successful metastasis of primary tumors. Rhabdosarcoma is a rare, early metastasizing tumor previously uncharacterized for ability to alter platelet function. It was found that human rhabdosarcoma cells (American Type Culture Collection) dose dependently induce biphasic aggregation of human blood platelets in heparinized platelet-rich plasma; aggregation responses could also be elicited in citrated plasma. Aggregation caused by rhabdosarcoma can be inhibited by apyrase treatment of either rhabdosarcoma or platelets, and by pretreatment of platelets with prostacyclin, cilostamide, inhibitors of thromboxane A2 production, or TMB-8; only apyrase and prostacyclin inhibited both phases of aggregation. Tumor cell supernatant contained only enough ADP to cause a negligible, reversible aggregation response. Hirudin, verapamil, and triazolam do not inhibit rhabdosarcoma-induced aggregation. Aggregation of platelets by rhabdosarcoma cells thus appears to involve ADP, from tumor cells and/or platelets, and platelet calcium mobilization and thromboxane A2 synthesis and release.

Adenosine Diphosphate↗
PubMed1989

Do chest physicians follow-up too many patients?

We have examined the pattern of attendance of 750 randomly selected regular attenders at a chest outpatient clinic and sought the patients' views on the frequency of their follow-up appointments and the possible consequences of discharge to the care of the general practitioners. In addition, the clinic doctors and the patients' general practitioners were asked about the appropriateness of the frequency of follow-up and whether the pattern of attendance should change or the patient be discharged. Patients were most commonly seen at three monthly intervals. Clinic doctors felt that 24% and general practitioners that 9% of patients attended too often while only 2% of patients felt that this was the case. Clinic doctors recommended discharge for 28% and general practitioners for 21% of patients. Sixty-nine per cent of patients felt that their condition would be unchanged or would improve if they were discharged to the care of their general practitioners. Our findings suggest that at least 20% of our patients should be discharged to the care of their general practitioners, and, if the patients are correct in their interpretation of the consequences of discharge, that as many as 70% could safely be discharged.

Adolescent↗
PubMed1989

A specific LTD4/LTE4-receptor antagonist improves pulmonary function in patients with mild, chronic asthma.

LY171883 is a new selective LTD4/LTE4-receptor antagonist. To evaluate the efficacy of LY171883, we studied 138 nonsmoking asthmatic patients, 18 to 65 yr old, in a double-blind, randomized block-design study. All patients were required to demonstrate a greater than or equal to 15% increase in FEV1 after inhaled bronchodilator use and were then randomly assigned to either LY171883 (600 mg) or placebo twice daily for 6 weeks. Assessment of efficacy was measured by inhaled metaproterenol use (mg/wk), symptoms, twice-daily peak expiratory flow, and weekly FEV1 measurements. LY171883-treated patients had improved FEV1 values upon completion of the treatment period compared with placebo recipients (p = 0.003). Metaproterenol use decreased in both groups, but treatment differences, though not statistically significant, favored LY171883 (p = 0.089). Of patients who used at least 23 mg/wk of metaproterenol (36 inhalations) at initiation of the study, those who received LY171883 used significantly less metaproterenol than those who received placebo (p = 0.007). LY171883 was well tolerated and reduced the need for a bronchodilator drug while improving pulmonary function. Results of this study support the hypothesis that leukotrienes LTD4 and/or LTE4 may be important in the pathogenesis of asthma in humans.

Acetophenones↗