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At least 145 records · Page 8Linked to original sources

Effects of angiotensin-converting enzyme inhibition on changes in left ventricular myocardial creatine kinase system after myocardial infarction: their relation to ventricular remodeling and function.

We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on changes in the myocardial intracellular creatine kinase (CK) system in relation to left ventricular (LV) remodeling and function in heart failure after myocardial infarction (MI) in rats. We compared the findings at 4 weeks after MI to those at 12 weeks after MI. LV weight and chamber size were significantly increased and percent fractional shortening (%FS) was decreased in untreated MI rats compared with normal control animals both at 4 and 12 weeks after MI. Animals with MI and treated with the ACE inhibitor temocapril showed significantly reduced LV weight and chamber size and increased %FS compared with untreated MI rats at 12 weeks after MI, but not at 4 weeks after MI. At 4 weeks after MI, no significant changes were found in the total creatine and relative distribution of each CK isoenzyme in either the temocapril-treated or untreated animals with MI compared with the normal controls. In contrast, at 12 weeks after MI, untreated MI rats showed significant reductions in the total creatine and mitochondrial and MM-CK fractions and increases in the MB- and BB-CK fractions compared with the controls. The alterations in the mitochondrial and MB-CK fractions were significantly attenuated after 12 weeks of ACE inhibition. Thus, LV myocardial energy metabolism is progressively impaired and its alteration is not related to the magnitude of geometric changes and LV dysfunction after MI. Most of the beneficial effects of ACE inhibition were observed at 12 weeks after MI. Our results may provide an insight into the therapeutic strategy of ACE inhibition in chronic heart failure after MI.

Angiotensin-Converting Enzyme Inhibitors↗

[Trichloroethylene concentration in the work environment in relation to the development of pneumatosis cystoides intestinalis].

Four cases of primary pneumatosis cystoides intestinalis (PCI) were studied in relation to occupational trichloroethylene (TRI) exposure. Three of the patients were exposed to TRI in the process of washing or polishing of camera lenses. The maximum concentration of TRI in the work environment of two PCI patients often exceeded 50 ppm, though the geometric mean concentrations were below this value. Monitoring of TRI exposure by measuring urinary TRI metabolites suggested that the third patient had been working in the environment with an 8-h time weighted average TRI concentration exceeding 50 ppm. Scrutiny of 19 PCI cases thus far collected by us revealed that i) three groups of patients (7 in total) were working in the same factories, ii) most of the PCI patients were workers in small-scale factories having poor working conditions, and iii) occupational TRI exposure is probably responsible for the development of primary PCI.

Adult↗

[Comparison of two neutralization tests, used in vesiculovirus Piry serodiagnosis].

A serological survey of Piry was undertaken of the sera of inhabitants of Catolância-Bahia State, Brazil. Serum results obtained by a vesiculovirus neutralization test of C6/36 cells read by ELISA are compared with those obtained by the classic technique, carried out on newborn mice. The agreement between the results was as high as 98.7% of the 204 sera tested and the neutralization test of C6/36 cells was chosen as the most suitable technique for the sero-survey testing.

Animals↗

[Dengue fever: a post-epidemic sero-epidemiological survey in an urban area setting at a northwestern county of São Paulo State, Brazil].

OBJECTIVE: The objective of this study was to evaluate the real size of the epidemics registered in the urban area of the county of Santa Bárbara D'Oeste, SP, Brazil, from April to June, 1995. The measurement of the epidemiological validity of the official surveillance system criteria and its positive predicted value were adopted as specific goals. METHODS: A sero-epidemiological survey was carried out over a sample of 1,113 sera from citizens of Santa Barbara D'Oeste, through a systematic random sampling of houses, five months after the end of the epidemics. Infection rates were compared with the infestation indexes by Aedes aegipty and the notified cases amongst the county sections. The importance of submitting patients with clinical suspicion of dengue to laboratory tests was discussed. RESULTS AND DISCUSSION: It was found that infection rates by dengue virus varied in the same direction and proportion as the presence of Aedes aegipty larvae reported by the "Breteau Index", as well as the number of cases reported by the official notifiable diseases surveillance system during the epidemics. A prevalence of 630 by 100 thousand inhabitants was found, a 15-fold rate when compared to the laboratory positive sera from cases detected by the surveillance system during the epidemics. A retrospective comparison with the surveillance reports, using serological results as a gold standard, also showed that the majority of dengue specific serum-positive individuals were not detected during the epidemics, otherwise cases that did not present serological reaction were notified exhibiting a low positive predictive value of clinical diagnosis (15,6).

Adolescent↗

Cytoplasmic body myopathy with hypertrophic cardiomyopathy.

A patient with cytoplasmic body myopathy presented muscle hypotonia from birth and developed progressive muscular atrophy and weakness, scoliosis, contracture of joints and cardiorespiratory failure. At the age of 17, he died of heart failure. Post mortem examination revealed severe hypertrophy of cardiac walls and generalized muscular atrophy. Microscopic examination showed many cytoplasmic bodies in skeletal muscle fibers and myofiber disarray in myocardium. No cases of cytoplasmic body myopathy with hypertrophic cardiomyopathy have been reported previously. It is suggested that the Z-line component is related to the formation of the cytoplasmic body in skeletal muscle and disarray in the cardiac muscle.

Adolescent↗

Recurrent cerebral embolism in a familial amyloid polyneuropathy patient who received partial liver transplantation from a living donor.

Cerebral embolism in relation to cardiac amyloidosis has not been widely noted. A 47-year-old woman who had been suffering from familial amyloid polyneuropathy (FAP) for 7 years was treated with partial liver transplantation from a living donor and her early postoperative course was uneventful. During the 391st to 613th postoperative day she experienced recurrent cerebral infarctions, but clinical examinations revealed no disorders capable of producing cerebral embolism. At autopsy splenic infarction and intracardiac thrombi adhering to the mitral valve and left atrium were found, and these areas showed severe amyloid deposition. Amyloid heart is considered to be one possible cause of systemic embolism.

Amyloid Neuropathies↗

An 80-year-old mitochondrial disease patient with A3243G tRNA(Leu(UUR)) gene presenting cardiac dysfunction as the main symptom.

MELAS is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, but cardiac involvement also frequently occurs. An 80-year-old female patient had been suffering from insulin-dependent diabetes mellitus and neurosensory hearing loss. At the age of 79 she suffered metabolic acidosis with persistent drowsiness and was subsequently found to have severe cardiac dysfunction. Muscle biopsy disclosed the presence of abnormal mitochondria, and the MELAS gene mutation (A3243G of the tRNA(Leu(UUR))) was demonstrated. It is noteworthy that this mitochondrial disease patient has survived until a great age, which shows the wide clinical spectrum of MELAS, especially in the age of onset.

Aged↗

Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents.

As a result of substantial advances in recent cancer biology, cell cycle regulation in the G1 phase has attracted a great deal of attention as a promising target for the research and treatment of cancer. Many of the important genes associated with G1 regulation have been shown to play a key role in proliferation, differentiation and oncogenic transformation and programmed cell death (apoptosis). Currently, a variety of "cytostatic" agents that affects G1 progression and/or G1/S transition are being evaluated in clinical trials. Flavopiridol is a potent inhibitor of cyclin-dependent kinases (CDKs). UCN-01 was originally found to be a PKC-selective protein kinase antagonist. More recent studies have revealed that this agent can also inhibit several CDKs and the checkpoint kinase CHK1. FR901228, MS-27-275 and SAHA are histone deacetylase inhibitors that induce changes in the transcription of specific genes via the hyperacetylation of histones. The proteasome inhibitor PS-341 disrupts the degradation process of intracellular proteins, including cell cycle regulatory proteins such as cyclins. R115777, SCH66336 and BMS-214662 are non-peptidic farnesyl transferase inhibitors that prevent p21 ras oncogene activation. Rapamycin derivative CCI-779 downregulates signals through S6 kinase and FRAP (FKBP-rapamycin associating protein), affecting the expression levels of mRNAs important for progression from G1 to S phase. 17-Allylaminogeldanamycin targets the Hsp-90 (heat shock protein-90) family of cellular chaperones regulating the function of signaling proteins. TNP-470 (AGM-1470), a fumagillin derivative shows antiangiogenic action through binding to MetAP-2 (methionine aminopeptidase-2). The antitumor sulfonamide E7070, causing a cellular accumulation in the G1 phase, has been shown to suppress the activation of CDK2 and cyclin E expression in HCT116 colorectal cancer cell line highly sensitive to the drug. With respect to several growth factor receptors such as EGFR, PDGFR, bFGFR and VEGFR, potent and specific inhibitors of receptor tyrosine kinases have been also examined as hopeful drug candidates. In this report, we review the current status of extensive efforts directed towards the discovery and development of new chemotherapeutic anticancer agents targeting cell cycle regulation in the G1 phase, with particular focus on the compounds undergoing clinical investigations.

Animals↗

Anticancer and antiviral sulfonamides.

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti- carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antitumor activity in vitro and in vivo. Although they have a common chemical motif of aromatic/heterocyclic or amino acid sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle perturbation in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others. Some of these compounds selected via elaborate preclinical screenings or obtained through computer-based drug design, are currently being evaluated in clinical trials. The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective tumor cell growth inhibitors, or for the treatment of different types of cancer. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Thus, at least two clinically used HIV protease inhibitors possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses. Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamido groups were also reported. Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups. Some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold.

Animals↗

Septicaemia in high risk neonates at a teaching hospital in Ile-Ife, Nigeria.

OBJECTIVES: To determine the incidence, predisposing factors, clinical features, bacteriological pattern and antibiotic sensitivity in septicaemia in high-risk newborns. DESIGN: A prospective study. SETTING: Neonatal unit, Ife State Hospital, a unit of the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Nigeria. SUBJECTS: All newborns admitted with clinical features and/or risk factors suggestive of neonatal septicaemia from February 1994 to March 1995. MAIN OUTCOME MEASURES: Culture results and mortality rates. RESULTS: The incidence of neonatal septicaemia among new born was 22.9 per 1000 livebirths. The predisposing perinatal factors were low socio-economic status, lack of antenatal care, maternal peripartum pyrexia and congenital malformations. Gram-positive bacteria were found to be the most prevalent causative organisms (59.4%). Staphylococcus aureus (36.2%), Pseudomonas aeruginosa (18.8%) and Coagulase negative Staphylococcus (15.9%) were the commonest causes of septicaemia. Meningitis and UTI were associated diagnoses in 16.7% and 18.2% of the septicaemic babies, respectively. The bacterial isolates showed a high degree of in-vitro antimicrobial resistance. However, all the isolates were sensitive to ofloxacin. Amongst the commonly used antibiotics, gentamicin had the lowest resistance. The overall mortality rate was 33.3%. CONCLUSION: Improvement in the socio-economic status of the populace and availability of affordable antenatal care would reduce the incidence of neonatal septicaemia in Nigeria. Continuous surveillance in every unit, as well as close attention to preventive strategies would be necessary to reduce morbidity and mortality from neonatal septicaemia. We recommend the inclusion of gentamicin in the initial treatment of septicaemia in the neonatal unit of OAUTHC, Ile-Ife, Nigeria.

Drug Resistance, Microbial↗

Latrogenic burns injury complicating neonatal resuscitation.

A case ofiatrogenic thermal injury in a newborn infant during resuscitation for perinatal asphyxia at a secondary health facility is described. The injury, with surface area coverage of about 4%, involved the lower limbs. This report highlights the poor newborn resuscitation skills of traditional medical practice.

Asphyxia Neonatorum↗

The analysis and diagnosis of unstable behavior of the blood vessel wall with an aneurysm based on noise science.

Previously, one of the authors developed a noninvasive measurement method of acceleration and deceleration during the expansion process of the blood vessel wall under pulsatile pressure flow by measuring the strain rate of the blood vessel wall using a supersonic Doppler effect sensor aided by computer analysis (DPC method). In this paper, on the basis of the analysis of chaos theory, that is, the complexity of science, the unstable behavior of the blood vessel wall with an aneurysm was investigated by identifying the characteristic DPC wave forms induced by the onset and progression of aneurysm. These results showed that unstable dynamic behavior of the blood vessel wall occurs due to the progression of the aneurysm. Furthermore, using the theoretical analysis of chaos, this unstable behavior of the blood vessel wall was quantified and the fundamental principle of a noninvasive diagnostic method of the progressive degree of aneurysm was proposed.

Aneurysm↗

Measurement of serum leptin in patients with chronic renal failure on hemodialysis.

BACKGROUND: Leptin, the product of the obese gene, is produced exclusively in fat cells. SUBJECTS, MATERIALS AND METHODS: To evaluate the clinical significance of measuring serum leptin in 56 patients with chronic renal failure on hemodialysis (HD), we measured leptin levels using radioimmunoassay in 34 normal volunteers and in 56 patients on HD. RESULTS: Normal serum leptin averaged 5.7 +/- 0.7 (mean +/- SEM) ng/ml, which correlated significantly (p < 0.001) with the body fat percentage as measured by bioelectrical impedance analysis. Serum leptin in HD patients ranged from 1.3 to 142 ng/ml. The mean serum leptin analyzed after the logarithmic conversion was 5.6 ng/ml, which was not significantly different from the normal control value, although the body fat percentage was significantly lower than normal volunteers. There was a significant (p < 0.01) positive correlation between body fat percentage and serum leptin in both normal controls and HD patients. The slope of the regression curve was steeper in HD patients than in normal controls. CONCLUSION: (1) serum leptin levels to body fat mass are significantly higher in HD patients than controls; (2) the variability is much wider in HD patients; and (3) a significant relation exists between percent body fat and log serum leptin, the relation being steeper in HD patients than in controls.

Adipose Tissue↗

Prognostic factors in childhood intra-abdominal sepsis.

Over a 36-month period, prognostic factors in childhood intra-abdominal abscesses were evaluated in fifty-five Nigerian children (38 boys [69.1%] and 17 girls [30.9%] aged 2 months-15 years (mean 8.9, SD 4.3 years). The mortality rate was 20%. The adverse prognostic factors were: a high fever, a positive blood culture, subphrenic location of abscesses, abscesses associated with a typhoid perforation, post-operative abscesses, presence of organ impairment, and multiple abscesses occurring together in the same patient. The age of the patient, duration of illness before hospitalization as well as the number and type of microorganisms cultured from the abscess did not have any influence on the prognosis in the children in this study.

Abdominal Abscess↗

[Acute myocardial infarction in elderly patients: medical and social problems].

The number of elderly patients with acute myocardial infarction has been increasing. However, the choice of treatment remains controversial. Medical records of 310 consecutive patients with acute myocardial infarction were reviewed. Two retrospective analyses were performed. 1) Patients were divided into the elderly group(70 years or more) and the younger group(under 70 years). In-hospital course and outcome were compared. 2) Pre-hospital performance status and living status were reviewed in the elderly group. Acute phase reperfusion therapy was performed in fewer patients in the elderly group(60.8% vs 71.9%, p < 0.01). The difference was most pronounced in cases of direct coronary angioplasty(28.6% vs 54.7%, p < 0.05). As a result, the rate of reperfusion success(74.8% vs 86.8%, p < 0.01) was lower in the elderly group. Moreover, the rates of in-hospital death(23.6% vs 6.8%, p < 0.005), pulmonary edema(20.3% vs 10.8%, p < 0.05), cardiogenic shock(11.9% vs 6.0%, p < 0.005), pneumonia(17.3% vs 3.0%, p < 0.005), and delirium(29.4% vs 12.0%, p < 0.001) were higher in the elderly group. Five patients in the elderly group and 3 patients in the younger group required rehabilitation because of worsened performance status. Six of them were non-reperfused patients. Elderly patients considered likely to become bed-ridden because of pre-existing physical disability at admission accounted for 28.9% of the total. Moreover, many elderly patients had poor support systems (8.4% were living alone, 21.0% were living only with their spouse or a child, 30.1% were widows or widowers). These results show that a lower acute phase reperfusion rate(especially angioplasty) resulted in a poor prognosis and worse performance status in elderly patients. Also 30% of patients were not good candidates for conventional treatment because of delirium, and that self-help in daily life is a fundamental goal for most elderly patients. Rapid and simple acute phase reperfusion, subsequent immediate mobilization, and early discharge are recommended for elderly patients with acute myocardial infarction.

Activities of Daily Living↗