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Biomedical subjects

P Liu

Publications and source records attributed to P Liu.

At least 235 records · Page 13Linked to original sources

Angiotensin-converting enzyme inhibition in myocardial infarction--Part 2: Clinical issues and controversies.

Over the past 10 years, several clinical studies have concluded that, in patients already receiving conventional therapies, angiotensin-converting enzyme (ACE) inhibitors further reduce the risk of death following myocardial infarction (MI). Post-MI ACE inhibitors have proven to be effective as long term therapy in high risk patients as well as when used for much shorter periods in a broad patient population. However, while considerable mortality data have been collected, the effects of ACE inhibitors post-MI on other cardiovascular outcomes have not been as well documented. In addition, a number of issues regarding the most effective use of these agents remain unresolved. This paper, the second of two parts, focuses on the clinical issues and controversies surrounding the use of ACE inhibitors following acute MI. The effects of ACE inhibitors on the outcomes of sudden death, nonsudden death, recurrent angina, mitral regurgitation and left ventricular dysfunction are reviewed and potential mechanisms of action are proposed. In addition, ACE inhibitor therapy is discussed in terms of patient selection criteria, choice of agent, optimal dosing regimen, concomitant use of other therapies and relative costs of treatment. Finally, potential mechanisms of action of ACE inhibitors are proposed for each of the outcomes examined.

Angiotensin-Converting Enzyme Inhibitors↗

Cardiac metastasis from primary cervical squamous cell carcinoma: three case reports and a review of the literature.

Clinically evident cardiac metastases from malignant neoplasms are uncommon, occurring most commonly in association with lung and breast carcinoma, lymphoma, leukemia and melanoma. The vast majority, over 90%, present with pericardial involvement. Squamous cell carcinomas of the cervix rarely produce cardiac metastases, with endomyocardia metastases being particularly rare. Three patients are reported who presented with primary squamous cell carcinoma of the cervix and developed this pattern of metastasis, one of whom was diagnosed at endomyocardial biopsy and the other two at autopsy. The paucity of such cases in the literature emphasizes the uniqueness of this phenomenon.

Adult↗

[The value of blood sedimentation test in early diagnosis of amniotic fluid embolism].

OBJECTIVE: To explore the value of peripheral blood sedimentation in early diagnosis of amniotic fluid embolism. METHOD: The contents of amniotic fluid were detected with blood sedimentation test in 15 cases of amniotic fluid embolism and 100 cases of normal pregnant women. RESULTS: The contents of amniotic fluid including particles of vernix caseasa, lanugo hair and epithelium cells were found in serum of amniotic fluid embolism cases but not found in cases of normal pregnant women. CONCLUSION: It suggested that the blood sedimentation test would be valuable for early diagnosis of amniotic fluid embolism.

Adult↗

[Effect of nitric oxide on rabbit baroreceptor activity].

The purpose of this study was to investigate the effect of exogenous nitric oxide (NO) on rabbit carotid sinus (CS) baroreceptor (BR) activity in vitro, especially in regard to determining whether the effect might be mediated by cGMP. The carotid sinus nerve (CSN) basal discharge could be divided into two groups: low-amplitude (LA) and high-amplitude (HA) ones. It was found that the HA discharge depended on superfusing-rate, but was not affected by several types of chemoreceptor stimuli, hence indicating a baroreceptive origin of the HA. Secondly, L-arginine (L-arg, 4.6-5.7 mmol/L) and nitroglycerin (NG, 0.07-0.88 mmol/L), precursor or donor of NO, excitated BR in a dose-dependent manner (P < 0.01). Lastly, inhibition of soluble guanylate cyclase (GC) with methylene blue (MB) affected neither the basal discharge of BR nor the response of BR to L-arg or nitroglycerin (NG).

Animals↗

An 80 Kb P1 clone from chromosome 3p21.3 suppresses tumor growth in vivo.

High frequencies of allelic loss on the short arm of chromosome 3 in small cell lung cancer (SCLC) and a number of other tumors suggest the existence of a tumor suppressor gene(s) within the deleted regions. Two small cell lung cancer lines, NCI H740 and GLC20, have been described which have homozygous deletions in the region 3p21.3. The deleted region overlaps with a 2 Mb fragment of human DNA present in the interspecies hybrid HA(3)BB9F, that suppresses tumor formation by mouse A9 fibrosarcoma cells. Human sequences from this cell hybrid were isolated using inter Alu PCR. From this starting point, a P1 contig was developed for the region of 450 Kb that is common to the homozygous deletions seen in the SCLC lines NCI H740 and GLC20 and is also present in HA(3)BB9F, the suppressed A9 hybrid. Individual P1 clones were assayed for their ability to suppress the tumorigenicity of the mouse fibrosarcoma cell line A9 as assayed by injection of transfected A9 cells into athymic nude mice. The introduction of one of the P1 clones into A9 cells resulted in suppression of tumor growth whereas two other P1 clones from the contig failed to suppress tumor formation in athymic nude mice. These data functionally delimit a tumor suppressor locus to a region of 80 kb within a P1 clone at 3p21.3.

Animals↗

Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial.

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P < .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P < .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P < .01).

Adult↗

Long-term potentiation in the perirhinal-hippocampal pathway is NMDA dependent.

The putative memory mechanism known as long-term potentiation (LTP) has been described in both NMDA-dependent and non-NMDA-dependent forms. The aim of the present study was to determine which of these forms described the LTP generated between perirhinal cortex (PRC) and hippocampus, two structures which have previously been implicated in learning and memory processes. In urethane-anaesthetized rats, high-frequency stimulation of the PRC induced a significant potentiation of PRC-hippocampal field potentials which was blocked by the NMDA receptor antagonist, MK-801. These data demonstrate that perirhinal-hippocampal LTP is NMDA-dependent and, moreover, that hippocampal-dependent learning which occurs during blockade of the NMDA receptor cannot be attributed to LTP of this pathway.

Animals↗

Localization of platelet-derived growth factor-stimulated phosphorylation cascade to caveolae.

Previously we showed that interleukin 1 beta stimulates the conversion of sphingomyelin to ceramide in the caveolae fraction of normal human fibroblasts. The ceramide, in turn, blocked platelet-derived growth factor (PDGF) stimulated DNA synthesis. We now present evidence that the PDGF receptor initiates signal transduction from caveolae. Cell fractionation and immunocytochemistry show caveolae to be the principal location of PDGF receptors at the cell surface. Multiple caveolae proteins acquire phosphotyrosine when PDGF binds to its receptor, but the hormone appears to have little effect on the tyrosine phosphorylation of non-caveolae membrane proteins. Five proteins known to interact with the phosphorylated receptor were found to be highly enriched in caveolae membrane. PDGF caused the concentration of three of these proteins to significantly increase in the caveolae fraction. Finally, PDGF stimulated the association of a 190-kDa phosphoprotein with the caveolae marker protein, caveolin. Therefore, ceramide may modulate PDGF receptor function directly in caveolae.

Caveolin 1↗

Direct connection between perirhinal cortex and hippocampus is a major constituent of the lateral perforant path.

Single-pulse stimulation of the perirhinal cortex (PRC) evoked field responses in the dorsal hippocampal CA1 region in urethane-anesthetized rats. In depth profiles conducted by moving the PRC stimulating electrode, the largest amplitude hippocampal potential was generated when the stimulating electrode was located within the perirhinal region. More dorsal (temporal cortex) or more ventral (lateral entorhinal cortex) stimulating sites elicited minimal hippocampal potentials. The hippocampal response was maintained during 100 Hz stimulation of the PRC, suggesting that it was monosynaptic, and high-frequency stimulation (400 Hz) of the PRC produced a significant potentiation of hippocampal CA1 field potentials (46.73 +/- 4.14%). When the PRC and the lateral perforant path (LPP) were stimulated separately, the depth/amplitude profiles obtained from a roving recording electrode located within the dorsal hippocampus were similar. In order to determine if fibers from PRC project to the hippocampus via the LPP, the PRC-CA1 and LPP-CA1 potentials were recorded prior to and during procaine (20%, 0.5 microliter) blockade of the LPP. A simultaneous loss of both potentials was observed immediately following procaine infusion, while a commissural control potential was unaffected. Both LPP and PRC potentials returned approximately 30-40 min later. Electrolytic lesions of PRC produced a significant decrease in the amplitude of LPP-hippocampal potentials when testing was conducted 4-5 days postlesion. Lesions of lateral entorhinal cortex or temporal cortex did not produce such effects. These data suggest that a direct pathway from perirhinal cortex to the dorsal hippocampal CA1 field can undergo long-term potentiation (LTP) and that this pathway makes a major contribution to the lateral perforant path.

Animals↗

Invasive vulvar carcinoma in two women infected with human immunodeficiency virus.

This report presents two HIV-infected women who developed invasive squamous cell carcinoma of the vulva. One patient was diagnosed with Stage II vulvar cancer 4 years after surgical excision of VIN. This patient underwent a hemivulvectomy and external-beam radiation therapy, but has subsequently developed recurrent vulvar cancer. The other patient was diagnosed with stage IV invasive vulvar cancer 1 year after the diagnosis of VIN and died of invasive vulvar cancer 11 months later. VIN should be considered a serious condition in HIV-infected women and clinicians should be careful to examine the vulva and perianal region in all HIV-infected women.

Acquired Immunodeficiency Syndrome↗

Effects of hypothyroidism on the vulnerability to ventricular fibrillation in dogs: a comparative study with amiodarone.

It has been shown that thyroid hormone has a significant effect on the heart and that suppression of thyroid function may contribute to the antiarrhythmic effect of amiodarone. The study was aimed at investigating the effects of hypothyroidism, compared with those of amiodarone, on vulnerability to ventricular fibrillation in dogs. In this study, 25 adult dogs were randomly divided into three groups: a hypothyroid group following total thyroidectomy (n = 9), an amiodarone group (n = 8, 400 mg per day, 4 weeks), and a control group (n = 8). Both amiodarone and control groups were subjected to sham surgery. Five to 8 weeks after surgery, ventricular fibrillation threshold and other electrophysiological parameters were determined. Right ventricular effective refractory period, monophasic action potential duration, and ventricular fibrillation threshold were significantly increased in both the thyroidectomized and amiodarone-treated animals. There was no significant change in monophasic action potential duration dispersion. The incidence of ventricular fibrillation during ischemia and reperfusion was significantly reduced in both treated groups compared with the sham-operated euthyroid controls. These observations suggest that hypothyroidism has a significant antifibrillatory effect in dogs. Homogeneous prolongation of repolarization and refractoriness may contribute to the antifibrillatory action of hypothyroidism.

Action Potentials↗

Effect of sinus denervation and vagotomy on c-fos expression in the nucleus tractus solitarius after exposure to CO2.

Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14-16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50- "mu"m section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.

Animals↗

Neutrophil-induced lung damage after hepatic ischemia and endotoxemia.

Administration of Salmonella enteritidis endotoxin (0.5 mg ET/kg) during reperfusion (RP) after short-term hepatic ischemia (20 min) caused severe liver injury induced by Kupffer cells and neutrophils and a high mortality rate. To investigate potential lung damage in this model, lung wet-to-dry weight ratios (W/D) and broncho-alveolar lavage (BAL) protein content were determined after 4 h of reperfusion. Both parameters increased significantly during RP/ET (W/D: 4.4 +/- 0.1; BAL: 639 +/- 30 micrograms/ml) compared to controls (W/D: 3.5 +/- 0.1; BAL: 332 +/- 17). The antioxidants Trolox or tirilazad mesylate (U-74006F) effectively reduced the BAL protein increase. Alveolar macrophages were not activated; however, neutrophils isolated from the lung microvasculature of RP/ET animals showed a 300% increase of spontaneous and PMA-induced superoxide formation compared to controls (spontaneous: 1.4 +/- 0.5 nmol O2-/h/10(6) cells; PMA: 2.2 +/- 0.4). Complement factors and TNF-alpha injection induced a similar priming of vascular neutrophils for superoxide generation. Vascular neutrophil activation highly correlated with the severity of lung injury. It is concluded that neutrophils accumulated in the lung microvasculature were the major source of the oxidant stress and mainly responsible for lung injury under these conditions. Antioxidants such as tirilazad mesylate (U-74006F) may have therapeutic potential for attenuating lung injury induced by remote organ trauma and a systemic inflammatory response.

Alanine Transaminase↗

Quantitative evaluation of aqueous isopropyl alcohol enhancement on skin flux of terbutaline (sulfate). 2. Permeability contributions of equilibrated drug species across human skin in vitro.

This paper demonstrates the usefulness of an equilibria-cotransport model for understanding the isopropyl alcohol-enhanced transport of an ionizable model compound, terbutaline in its sulfate salt form, through human skin in vitro. With the same isopropyl alcohol concentrations (0 - 80% v/v) present at both sides of skin, the permeation experiments were conducted using split-thickness skin and dermis membranes. The equilibria-cotransport model was consistent with total terbutaline flux and a terbutaline-to-sulfate flux ratio, both increased with increasing isopropyl alcohol and/or terbutaline sulfate concentrations. From the saturated drug solutions, aqueous isopropyl alcohol enhanced terbutaline skin flux about 10 - 100-fold with the maximum at 60 - 80% isopropyl alcohol. This overall flux enhancement was qualitatively separated into the contributions of isopropyl alcohol effects on both equilibrated donor concentrations and skin permeabilities of protonated terbutaline, terbutaline-sulfate ion pair anion, and neutral terbutaline-sulfate (2:1) ion triplet. In addition to altering the species equilibria, isopropyl alcohol was found to enhance the transport of both neutral and ionic species of terbutaline sulfate across stratum corneum.

1-Propanol↗