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At least 109 records · Page 6Linked to original sources
PubMed2002

Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis.

BACKGROUND: Although a high incidence of myocardial adrenergic denervation has been reported in patients with familial amyloid polyneuropathy, assessment of cardiac sympathetic nerve function has not been available in patients with AL (primary) amyloidosis. METHODS: To test the hypothesis that myocardial sympathetic nerve innervation might be impaired and variable according to the presence or absence of clinical autonomic abnormalities and congestive heart failure in AL amyloidosis, we examined 25 patients by use of iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: Ten of the 16 patients without autonomic symptoms and 5 of the 9 patients with autonomic neuropathy showed congestive heart failure. The heart/mediastinal activity (H/M) ratio (1.53 +/- 0.06 vs 1.29 +/- 0.05 at 3 hours, P <.001) and myocardial washout ratio (41.5% +/- 4.8% vs 30.8% +/- 4.0%, P <.001) of MIBG were significantly increased in patients without autonomic symptoms compared with patients showing autonomic neuropathy. In patient groups with and without autonomic dysfunction, patients demonstrating congestive heart failure exhibited a significantly decreased H/M ratio and increased washout compared with patients with no heart failure, and left ventricular fractional shortening was positively correlated with the H/M ratio and inversely correlated with the washout ratio. There were significant correlations between the low-frequency component of the heart rate variability and the H/M ratio and washout ratio in the entire patient population. CONCLUSIONS: Patients with AL amyloidosis and no autonomic dysfunction showed variable degrees of enhanced cardiac adrenergic neuronal activity with presynaptic sympathetic dysfunction. In contrast, patients with AL amyloidosis and autonomic neuropathy exhibited prominent myocardial adrenergic denervation with normal or impaired sympathetic neural function of the heart. This study demonstrates that myocardial uptake and turnover of MIBG in patients with AL amyloidosis are heterogeneous and dependent on the presence or absence of congestive heart failure and cardiac autonomic dysfunction.

3-Iodobenzylguanidine↗
PubMed1998

Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase.

Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH 3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flattened phenotype of the nontransformed parental cells. The mechanism of detransformation induced by this agent had not been determined. Here, we demonstrate that depudecin inhibits histone deacetylase (HDAC) activity effectively both in vivo and in vitro. Depudecin induces similar morphological reversion in v-ras transformed NIH 3T3 cells as do other naturally occurring HDAC inhibitors such as trichostatin A or trapoxin. It competitively inhibits the binding of [3H]trapoxin in vitro and the nuclear binding of a trapoxin-coumarin fluorophore in vivo, suggesting that depudecin shares a nuclear binding protein and site on that protein with trapoxin. Furthermore, depudecin induces hyperacetylation of histones in a dose-dependent manner and at concentrations comparable with that required for detransformation. An in vitro histone deacetylase assay, using purified recombinant HDAC1, reveals that depudecin inhibits 50% of the enzyme activity at a concentration of 4.7 microM. These results demonstrate that depudecin is a novel HDAC inhibitor and suggest that its ability to induce morphological reversion of transformed cells is the result of its HDAC inhibitory activity.

3T3 Cells↗
PubMed1998

A role for histone deacetylase activity in HDAC1-mediated transcriptional repression.

Treatment of mammalian cells with small molecule histone deacetylase (HDAC) inhibitors induces changes in the transcription of specific genes. These changes correlate directly with an increase in the acetylation levels of all four core histones in vivo. Antibodies directed against endogenous HDAC1, HDAC2, or HDAC3 immunoprecipitate histone deacetylase activity that is inhibited in vitro by the small molecule trapoxin (TPX), and all three HDACs are retained by a TPX-affinity matrix. HDAC1 and HDAC2 are associated in HeLa cells in a complex that is predominantly separate from an HDAC3 immune complex. Both Jurkat HDAC1 and HeLa HDAC1/2 immune complexes deacetylate all four core histones and recombinant HDAC1 deacetylates free and nucleosomal histones in vitro. Purified recombinant HDAC1 deacetylates core histones in the absence of protein cofactors. Site-directed mutagenesis was used to identify residues required for the enzymatic and structural integrity of HDAC1. Mutation of any one of four conserved residues causes deleterious effects on deacetylase activity and a reduced ability to bind a TPX-affinity matrix. A subset of these mutations also cause a decreased interaction with the HDAC1-associated proteins RbAp48 and mSin3A. Disruption of histone deacetylase activity either by TPX or by direct mutation of a histidine presumed to be in the active site abrogates HDAC1-mediated transcriptional repression of a targeted reporter gene in vivo.

Amino Acid Sequence↗
PubMed1999

Phthalascidin, a synthetic antitumor agent with potency and mode of action comparable to ecteinascidin 743.

A series of totally synthetic molecules that are structurally related to the marine natural product ecteinascidin 743 (Et 743) has been prepared and evaluated as antitumor agents. The most active of these, phthalascidin, is very similar to Et 743 with regard to in vitro potency and mode of action across a variety of cell types. The antiproliferative activity of phthalascidin (IC50 = 0.1-1 nM) is greater than that of the agents Taxol, camptothecin, adriamycin, mitomycin C, cisplatin, bleomycin, and etoposide by 1-3 orders of magnitude, and the mechanism of action is clearly different from these currently used drugs. Phthalascidin and Et 743 induce DNA-protein cross-linking and, although they seem to interact with topoisomerase (topo) I (but not topo II), topo I may not be the primary protein target of these agents. Phthalascidin and Et 743 show undiminished potency in camptothecin- and etoposide-resistant cells. Phthalascidin is more readily synthesized and more stable than Et 743, which is currently undergoing clinical trials. The relationship of chemical structure and antitumor activity for this class of molecules has been clarified by this study.

Antineoplastic Agents, Alkylating↗
PubMed2003

Use of biomarkers of sub-clinical infection, nutrition and neonatal maturity to interpret plasma retinol in Nigerian neonates.

Using the World Health Organization criterion, the prevalence of sub-clinical vitamin A deficiency can be assessed using plasma retinol concentrations <0.7 micromol/l. However, plasma retinol can be depressed by infection; thus, the use of this criterion alone may overestimate deficiency. In the present study, we investigated the usefulness of the acute-phase proteins (APP) alpha1-antichymotrypsin (ACT) and alpha1-acid glycoprotein (AGP), plasma carotenoids and anthropometric and gestational indices to interpret plasma retinol in the blood of 192 apparently healthy Nigerian neonates collected randomly during days 1-20 postpartum. The mean weight (2.64 kg) and length (0.458 m) of the neonates and plasma concentrations (geometric mean, micromol/l) of retinol (0.54), alpha-carotene (0.072), ss-carotene (0.076) and lutein (0.080) were low. The prevalence of vitamin A deficiency was 72 %, indicating a severe public health problem. Babies who were of low birth weight (P<0.003) or premature and low birth weight (P<0.023) had significantly lower retinol concentrations than full-term normal weight babies. Thirty-two neonates had abnormal ACT and forty-four abnormal AGP concentrations. Positive correlations between retinol and ACT (r 0.186, P=0.05) and AGP (r 0.31, P=0.0001) during days 1-5 may be due to the increasing plasma retinol from maternal milk and a coincidental increasing capacity to synthesise APP. Subsequently, negative correlations between retinol and ACT (r -0.28, P=0.02) and AGP (r -0.29, P=0.018) from day 6 onwards reflected the continuing increase in plasma retinol, but no further increase in the APP. Overall, weight, ACT, lutein and age explained 30 % of the variance in retinol, but lutein was the most significant (r(2) 0.18, P<0.0001). Hence, the distribution of plasma retinol concentrations in this group of neonates was more strongly linked with nutrition (via the surrogate marker lutein) than infection.

Biomarkers↗
PubMed2000

An acoustically evoked short latency negative response in profound hearing loss patients.

In our auditory brainstem response (ABR) tests, a peculiar V-shaped negative wave at around 3 4 ms latency was observed. At present, this acoustically evoked short latency negative response (ASNR) is poorly understood. In order to study its appearance and origin, the ABR data of 3104 tests during 1980-98 were reviewed. The ASNR was found only in profound hearing loss ears under intense stimuli (80-120 dB nHL). Out of the total 653 profound hearing loss patients (981 ears), the click-evoked ASNRs were present in 80 patients (12.3%), 117 ears (11.9%). The age range was from 8 months to 70 years. Demographic outcome revealed significant higher appearance rates in young subjects especially in the 20-30 years group. The ASNR was excluded from an artifact by its reproducibility over time, equipment and institutes. Moreover, it became absent after external auditory canal occlusion, which simply blocked the air conduction without any influence upon scalp potentials or equipment. It had neural response characteristics that the latency and amplitude shortened and increased respectively in response to the increase of stimulus intensity. Because the peculiar V-shaped waveform obviously differs from ABR, the ASNR was not interpreted as a potential generated from the conventional auditory pathway. On the other hand, the ASNR individuals were of good vestibular function in sharp contrast with their poor hearing. This suggests the probable relation between the ASNR and the vestibular system. The saccule and vestibular nucleus are hypothesized to be the sense organ and the origin of the response respectively.

Acoustic Stimulation↗
PubMed2002

Can sedation reduce the cardiac stress during gastrointestinal endoscopy? A study with non-invasive automated cardiac flow measurement by color Doppler echocardiography.

BACKGROUND: Upper gastrointestinal endoscopy (UGIE) may cause some cardiac stress. The effect of sedation on hemodynamics during UGIE has not been fully studied, and therefore the aim of this study was to clarify whether or not sedation can reduce cardiac stress dufing UGIE. METHODS: Eight normal male volunteers undergoing UGIE with sedation (0.1 mg/kg of midazolam) and without it (two endoscopies per volunteer in random order) were monitored throughout the procedure by means of electrocardiogram, blood pressure and peripheral oxygen saturation (SpO2). Cardiac output was measured at six points before, during and after endoscopy from automated cardiac flow measurement by color Doppler echocardiography. Serum norepinephrine, epinephrine, dopamine and ACTH concentrations were measured before and after the examination. RESULTS: No significant differences in heart rate, systolic blood pressure, rate-pressure product, cardiac output and left ventricular work index were observed between the sedated and non-sedated groups. SpO2 hardly changed during endoscopy in the non-sedated group, but decreased slightly in the sedated group (P = 0.075). Although all serum catecholamine concentration changes were within normal limits in both groups, after endoscopy only epinephrine concentration was significantly lower in the sedated group than in the non-sedated group (P = 0.0027). CONCLUSIONS: Conscious sedation with midazolam does not reduce the cardiac stress during UGIE.

Adrenocorticotropic Hormone↗
PubMed1988

Neonatal bacteraemia in Wesley Guild Hospital, Ilesha, Nigeria.

In a study on neonatal bacteraemia among the high-risk neonates admitted into our neonatal unit at Wesley Guild Hospital, Ilesha, the incidence of bacteraemia in babies born in the hospital was 17/1000 live births and 71.6/1000 total admissions into the unit. Gram-negative bacteria accounted for about 58.1% of bacteria isolated and Staphylococcus aureus for 62% of the isolated Gram-positive bacteria. Among the commonly used antibiotics, gentamicin is the most favoured by the sensitivity test. S. aureus appeared more sensitive to erythromycin than to cloxacillin or ampicillin. The present policy of using the combination of gentamicin and cloxacillin and/or ampicillin is adequate for most agents encountered and therefore should continue. It is suggested that proper antenatal care, adequate supervision of delivery, better neonatal care and provision of better laboratory facilities will help to reduce the incidence of neonatal bacterial infection, improve the management of neonatal infection and reduce the morbidity and mortality from bacterial infection.

Anti-Bacterial Agents↗
PubMed1991

Childhood intussusception in Ile-Ife, Nigeria.

A retrospective review of 41 intussusceptions encountered in 39 children seen over an 8-year period in Ile-Ife, Nigeria is presented. Most cases (61.5%) occurred in infancy. This contrasts with previous reports from Nigeria where intussusception has been presented as being commoner in older children. Vomiting, abdominal pain, excessive crying and passage of bloodstained stools were the main presenting symptoms. An abdominal mass was palpable in only 28.2% of patients. Generally, patients presented late in hospital with only two (5.1%) arriving within 24 hours of the onset of illness. Hydrostatic reduction with barium enema was attempted in these two patients, and it successfully reduced the intussusception in one and caused partial reduction in the other. Nineteen patients (46.3%) required bowel resection. There were nine deaths, giving a mortality rate of 23.1%. The relatively high bowel resection and mortality rates were attributed to the delay in seeking medical treatment.

Adolescent↗
PubMed1997

Total and percentage body water in healthy Nigerian children aged 5-15 years.

Bioelectrical impedance was used to measure total body water in Nigerian children in a clinical setting. Total body water and percentage body water were determined in 454 boys and 450 girls, all healthy Nigerian children aged between 5 and 15 years. The age range and total body water were similar in both sexes but percentage body water was significantly higher in boys than in girls (p = 0.000001). Total body water increased with age in both boys and girls. Percentage body water increased with age but not significantly so in boys (p > 0.076) and decreased significantly with age in the girls (p = 0.008), an indication of differences between the sexes in how the proportion of body fat mass changed with age. These data are very similar to those reported in the literature. The bioelectrical impedance method for body water determination is non-invasive, cheap, portable and well accepted by children. Its more general clinical application in paediatric practice is recommended.

Adolescent↗
PubMed1997

Fat mass, fat mass percentage, body mass index, and mid-upper arm circumference in a healthy population of Nigerian children.

We determined body fat mass, body mass index, and mid-upper arm circumference, in 5-15-year-old Nigerian children consisting of 454 (50 per cent) males and 450 (50 per cent) females. We derived regression equations between body fat mass and age, body mass index, and mid-upper arm circumference for each sex. The mean of age and height were similar in both sexes, while that of fat mass, percentage fat mass, body mass index, and mid-upper arm circumference were significantly higher in the female than male. Percentage fat mass varied between 3.02 and 32.16, and 1.88 and 53.84 in males and females, respectively (P = 0.0000). The percentage fat mass increased slightly with age (but significantly) in the female and decreased slightly with age in the male. Based on the US standards 164 (18 per cent) of the children were obese. We conclude that with improvement in living standards, childhood obesity may become a medical problem in Nigeria.

Adipose Tissue↗
PubMed2005

Prevalence of congenital malaria in Ile-ife, Nigeria.

The study was designed to determine the prevalence of congenital malaria, cord blood and placental malaria parasitaemia and the prevalence of clinical manifestations of congenital malaria. Ile-Ife is a holoendemic area for malaria. Placental, cord and peripheral blood smears of 120 newborn babies were examined for malaria parasites. They consisted of 104 (86.7 per cent) full term babies and 16 (13.3 per cent) preterm babies. Positive parasitaemia was found in 56 (46.7 per cent) of peripheral blood smears, 68 (56.7 per cent) and 65 (54.2 per cent) of the placental and cord blood smears respectively. There were strong associations between placental malaria and cord malaria parasitaemia and congenital malaria (p < 0.001). Congenital malaria has a high prevalence in Ile-Ife. There is a paucity of its clinical manifestations in the newborn. Only two babies had fever within 48 hours of birth.

Adult↗
PubMed2006

Comparative study of nutritional status of urban and rural Nigerian school children.

Nutritional assessment in the community is essential for accurate planning and implementation of intervention programmes to reduce morbidity and mortality associated with under-nutrition. The study was, therefore, carried out to determine and compare the nutritional status of children attending urban and rural public primary schools in Ife Central Local Government Area (ICLGA) of Nigeria. The schools were stratified into urban and rural, and studied schools were selected by balloting. Information obtained on each pupil was entered into a pre-designed proforma. The weight and height were recorded for each pupil, and converted to nutritional indices (weight for age, weight for height, height for age). A total of 749 pupils (366 and 383 children from the rural and urban communities, respectively) were studied. The overall prevalent rates of underweight, wasting and stunting were 61.2, 16.8 and 27.6%, respectively. In the rural area these were 70.5, 17.8 and 35.8%, while in the urban they were 52.2, 15.9 and 19.8%, respectively. The mean nutritional indices (Weight for Age, Weight for Height and Height for Age) were found to be significantly lower among the rural pupils than urban pupils (P < 0.001 in each case). The present study shows that malnutrition (underweight, wasting and stunting) constituted major health problems among school children in Nigeria. This is particularly so in the rural areas. Therefore, prevention of malnutrition should be given a high priority in the implementation of the ongoing primary health care programmes with particular attention paid to the rural population.

Body Height↗
PubMed2002

Saccular origin of acoustically evoked short latency negative response.

OBJECTIVES: To determine the origin of the acoustically evoked short latency negative response (ASNR), a peculiar V-shaped response at about 3 to 4 milliseconds found during auditory brainstem response recordings. Previous reports demonstrated that the ASNR is present only in ears with profound hearing loss under intense stimulation. It has already been excluded as any kind of artifact. The individuals with ASNR had good vestibular function in spite of their poor hearing, suggesting a relation between the ASNR and the vestibular system. The saccule and vestibular nuclei are hypothesized to be the sense organ and the generator of the response, respectively. The current study tested the saccular function for ears with ASNR and searched for ASNR in ears with a functionless cochlea. STUDY DESIGN: Prospective study. SETTING: Academic tertiary referral center. PATIENTS: Twenty patients with bilateral profound hearing loss, aged 6 to 62 years, including 16 cochlear implant recipients. Twelve healthy participants with normal hearing, aged 23 to 30 years, served as the control group. INTERVENTIONS: Recordings of vestibular evoked myogenic potential (VEMP) and auditory brainstem responses. MAIN OUTCOME MEASURES: The presence or absence of ASNR in ears with cochlear implants. The presence or absence and threshold of VEMP in ears with ASNR versus ears without ASNR. RESULTS: ASNR was recorded by sound stimulation from three ears with unaided cochlear implants, a model of functionless cochlea. VEMP was evoked by sound stimulation to all the nine ASNR ears without threshold difference from normal control ( > 0.05), implying normal saccular function for the ASNR ears. For the ears with profound hearing loss and absence of ASNR, about two thirds were considered to have saccular afunction because of absence of VEMP. The other third displayed VEMPs with higher threshold than normal control ( < 0.01), indicating saccular hypofunction. Furthermore, ASNR and VEMP were elicited from an ear diagnosed with semicircular canal hypofunction. CONCLUSIONS: It is clear that the presence of ASNR is dependent not on residual hearing but on normal saccular function. On the basis of these results, the authors believe ASNR to be saccular in origin.

Acoustic Stimulation↗
PubMed2007

Electrode independence in intraneural cochlear nerve stimulation.

OBJECTIVES/HYPOTHESIS: We have previously reported feline electrophysiological and anatomical studies focused on the development of an intraneural auditory neuroprosthesis. Because only the tips of the electrodes implanted in the cochlear nerve are the stimulating elements that abut the nerve axons, we hypothesize that intraneural stimulation will be highly focal in nature. In this article, we report the electrophysiological characterization of the selective activation of subpopulations of cochlear nerve fibers via electrodes implanted in feline cochlear nerve. STUDY DESIGN: We have used a forward-masking paradigm to estimate the extent of stimulation overlap produced by pairs of electrodes implanted into the cochlear nerve. METHODS: The technique uses sequential stimulation via masking and probe electrodes and monitoring of the electrically evoked auditory brain stem response as an index of cochlear nerve fiber recruitment. We investigated overlap in all possible electrode pair combinations. RESULTS AND CONCLUSION: Many electrode pairs manifest virtually no overlap in the subpopulations of fibers excited by perithreshold stimuli, whereas most had considerable overlap at higher stimulation levels. However, we also noted that our measured overlap was similar across electrodes possibly because of lack of specificity of the whole nerve electrically evoked auditory brain stem response as an assay for this parameter. These findings indicate that direct cochlear nerve stimulation via intraneural electrodes provides selective excitation of small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve stimulation may selectively evoke narrow-band frequency percepts.

Animals↗
PubMed1999

Percutaneous cephalic vein approach for permanent pacemaker implantation.

Implantation of permanent pacemaker leads into the cephalic vein within the deltopectoral groove is enhanced by introduction of a flexible guidewire into the brachial vein at the antecubital fossa, which is then advanced to the subclavian vein. The cephalic vein within the deltopectoral groove is easily found by incision with the guidewire as a marker. A pacing lead or leads can be inserted along the guidewire or by using a sheath advanced over the guidewire. The procedure was performed on 32 patients and the pacing leads of 28 procedures (DDD 15, VDD 9 and WI 4) were inserted using the cephalic vein without complications.

Aged↗
PubMed1989

The prevalence of bacteriuria among high risk neonates in Nigeria.

Among the 446 high risk neonates studied for significant bacteriuria and pyuria in the neonatal wards of the Obafemi Awolowo University teaching hospital Complex, Ile-Ife, 7.6% and 5.8% were positive for significant bacteriuria and pyuria respectively, while none of the 81 infants in the control group were positive. Males and females were similarly affected and there was no seasonal variation in the prevalence of pyuria or bacteriuria. It is noteworthy that 25 (96%) of the 26 pyuria neonates also had bacteriuria emphazising the significance of pyuria as a possible screening method for urinary tract infections in neonates. The clinical problems in the neonates studied included prematurity, low birthweight, neonatal jaundice, fever, CNS symptoms, ophthalmia neonatorum, prolonged rupture of the membranes (PROM), respiratory distress, septic cord/skin, diarrhoea, vomiting and feeding problems. Only prematurity and low birthweight were significantly associated with bacteriuria in the neonates studied. The organisms encountered in this study were Escherichia coli (58.4%), Klebsiella species (35.3%) and Proteus species (5.9%). Of the bacterial isolates, 67% were sensitive to Ampicillin and 97% to Gentamycin. The combination of these antibiotics was effective in all cases in the present study. The study has highlighted the need for routine urine culture in our high risk neonates.

Bacteriuria↗