Nosocomial and community acquired uropathogenic isolates of Proteus mirabilis and antimicrobial susceptibility profiles at a university hospital in Sub–Saharan Africa

ObjectiveTo ascertain antimicrobial susceptibility profile of Proteus mirabilis (P. mirabilis) from clinical urine specimens at a university hospital in the spate of its recorded increasing resistance patterns.MethodsThe study was retrospective in nature. Data generated from urine cultures of patients at University of Calabar Teaching Hospital for a period of five years (2004–2009) were compiled. Relevant information obtained were age and gender of patients, organisms recovered and their antibiotic susceptibility patterns. P. mirabilis was identified using standard laboratory procedures.ResultsP. mirabilis showed the highest resistance against ampicillin, cloxacillin, amoxicillin, tetracycline, co-trimoxazole, erythromycin and chloramphenicol (100%–37.2%) while colistin, ofloxacin, ciprofloxacin, ceftriaxone, nalidixic acid and nitrofurantoin recorded the highest activity (59.1%–96.9%) with no drug recording 100% activity. The resistance of the nosocomial isolates of the organism were significantly higher than the community acquired isolates against that of the common antibiotics in use (P<0.05).ConclusionsExtreme caution should be exercised in antibiotic administration in hospital setting and the potential benefits adequately assessed while control of nosocomial infections be given a priority so as to limit the spread of resistant bacteria.     

Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.     

Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril

Guidelines recommend combining β-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in which carvedilol (C, 20 then 40 mg/day) or a control renin-angiotensin blocker, valsartan (V, 160 then 320 mg/day) were added to L. Ambulatory blood pressure (ABP) and heart rate monitoring was performed at the end of each period. Rate-pressure product (RPP, systolic BP × heart rate, an indicator of cardiac oxygen consumption) was measured over 24 hours, daytime (6 am to midnight), and nighttime (midnight to 6 am) periods. Variability (standard deviation and range) of RPP, BP, and heart rate was also investigated. After 4 weeks, mean 24-hour systolic BP was about 8 mm Hg lower when either V or C was added to L (P < .01 each). Heart rate was consistently lower with C (8 beats/min over 24 hours, P < .000) but was slightly increased with V (about 2 beats/min, P = NS). Consequently, C lowered RPP to a greater degree than V over 24 hours (about 8% vs. 2%, P < .000) and during daytime and nighttime periods (P < .000 each). In addition, RPP variability (SD but not range) was consistently lower on C than V. When added to L, C reduces the mean and variability (SD) of 24-hour heart rate and cardiac workload to a greater degree than valsartan. These effects may contribute to the outcome benefits observed with β-blocker–ACE inhibitor combinations.     

111In-oxine platelet survivals in thrombocytopenic infants

Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous 111In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the 111In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to- liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.     

Four categories of gamma-globin gene triplications: DNA sequence comparison of low G gamma and high G gamma triplications

The human fetal gamma chains are produced by closely linked G gamma and A gamma genes, and unequal crossing over between them leads to gamma gene deletions and triplications. Nine gamma gene triplications from seven ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of heterozygotes and for the presence of polymorphic XmnI restriction sites 5' to the gamma genes. Four categories of triplication were found: I had low G gamma and low Hb F values and lacked XmnI sites 5' to the three gamma genes [---]. II had high G gamma and slightly elevated Hb F values but was also [---]. III was similar to II, except that XmnI was [+--]. IV had very high G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case each of triplications I and IV were cloned into Charon 35. For both, the two 5' gamma gene code for G gamma chain, while the 3' gamma gene codes for A gamma chain. DNA sequencing showed that the unequal crossover occurred between 472 and 398 base pairs (bp) 5' to the gamma gene Cap sites (- 472 and -398) for the type IV triplication and between -271 and codon 136 for the type I triplication. In addition, type I had a 4-bp deletion of AGCA from -225 to -222. The high G gamma values of the type IV triplication are explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI sites 5' to the G gamma genes. We hypothesize that the low G gamma value of the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to inactivation of the middle G gamma gene by the AGCA deletion at -225 to -222.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.