Inadequate control of lipid levels in patients with a previous myocardial infarction

AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.     

The facC gene of Aspergillus nidulans encodes an acetate-inducible carnitine acetyltransferase

Mutations in the facC gene of Aspergillus nidulans result in an inability to use acetate as a sole carbon source. This gene has been cloned by complementation. The proposed translation product of the facC gene has significant similarity to carnitine acetyltransferases (CAT) from other organisms. Total CAT activity was found to be inducible by acetate and fatty acids and repressed by glucose. Acetate-inducible activity was found to be absent in facC mutants, while fatty acid-inducible activity was absent in an acuJ mutant. Acetate induction of facC expression was dependent on the facB regulatory gene, and an expressed FacB fusion protein was demonstrated to bind to 5' facC sequences. Carbon catabolite repression of facC expression was affected by mutations in the creA gene and a CreA fusion protein bound to 5' facC sequences. Mutations in the acuJ gene led to increased acetate induction of facC expression and also of an amdS-lacZ reporter gene, and it is proposed that this results from accumulation of acetate, as well as increased expression of facB. A model is presented in which facC encodes a cytosolic CAT enzyme, while a different CAT enzyme, which is acuJ dependent, is present in peroxisomes and mitochondria, and these activities are required for the movement of acetyl groups between intracellular compartments.     

Development and validation of transient isotachophoretic capillary zone electrophoresis for determination of peptides

Although capillary zone electrophoresis (CZE) is known for its high resolution power and low mass detection limits, the concentration detection limits are rather poor when ultraviolet absorbance detection is used. To overcome this limitation, several on-column transient isotachophoresis (tITP) protocols have been developed and validated for the determination of both cationic and anionic model peptides, separately. Using this preconcentration method, up to 72% of the capillary can be filled with sample solution, without any loss in resolution. Thus, without any modification of the hardware set-up, the sensitivity is increased about two orders of magnitude. For the model cationic peptides (gonadorelin, angiotensin II) good linearity and reproducibility is observed in the 20 to 100 ng/mL concentration range. For the anionic peptides (N-t-Boc-Pentagastrin and two related peptides), a tITP method was developed using a dynamically coated capillary. The coating was prepared by adding Fluorad FC-135 to the leading electrolyte buffer. In this way a positively charged bilayer was formed on the inside of the capillary, producing an electroosmotic flow towards the outlet using reversed polarity conditions. In this way, acceptable analysis times were achieved. Using the developed tITP method, up to 72% of the capillary can be filled with sample solution as well. The anionic peptides are separated even better than when using CZE conditions. Linearity and reproducibility in the 20-100 ng/mL range proved to be excellent.     

Behavioral thermoregulatory response to maitotoxin in mice

Many types of marine algal toxins induce marked hypothermic responses in mice. However, it is not known if the thermoregulatory response to these toxins results from dysfunction in the control of core temperature (Tc) or is a coordinated response to lower Tc as occurs with a variety of xenobiotic insults. Female CD-1 mice were administered purified maitotoxin (338 ng/kg; IP) and placed in a temperature gradient for 5 h that permitted the selection of ambient temperatures (Ta) ranging between 15 and 37 degrees C. Tc was monitored simultaneously by radiotelemetric probes that were surgically implanted into the abdominal cavity at least one week before maitotoxin injection. Maitotoxin led to a rapid reduction in Tc from 37 to 34 degrees C within 30 min after injection. There was a simultaneous 4 degrees C reduction in Ta selected by mice within 15 min after injection. Selected Ta recovered rapidly, increased above baseline for approximately one hour, then remained near baseline levels for the remainder of the test period in the gradient. Tc remained approximately 1 to 2 degrees C below control levels throughout the test period. In the temperature gradient, mice can select Ta's warm enough to offset the hypothermic effects of maitotoxin. That cooler Ta's are selected initially after maitotoxin injection suggest that the central neural control of body temperature is affected by the toxin. We postulate that the hypothermic response may represent an adaptive response to enhance survival following exposure to polyether toxins.     

Eosinophil-specific biological activity of recombinant ovine interleukin-5

Recombinant ovine interleukin-5 (rovIL-5) expressed from Chinese hamster ovary (CHO) cells was tested for cell-specific bioreactivity, in vitro, in a soft agar clonogenic assay and in an enzyme-based microassay for eosinophil potentiating activity (EPA). In soft agar assays, colony and cluster formation from sheep bone marrow cells (SBMC) incubated with rovIL-5 was significantly enhanced compared with SBMC incubated with control supernatants from mock-transfected CHO cells. Colony analysis at 14 days demonstrated that for three separate rovIL-5 preparations 45%, 61% and 66% of colonies were eosinophilic, as were 55%-71% of clusters. In contrast, no eosinophil colonies were detected in parallel control cultures. RovIL-5 was also shown to possess potent and dose-responsive EPA, on the basis of eosinophil peroxidase (EPO) and arylsulphatase (EAS) assay in 7 day SBMC cultures. This activity was inhibited in a dose-responsive manner by TRFK-5, a rat anti-murine IL-5 monoclonal antibody (MAb) previously shown to have cross-reactivity in the ovine EPA assay. The results demonstrate that rovIL-5 exhibited eosinophil-specific properties similar to those of IL-5 derived from other mammalian species.     

Effect of topical anesthetic use on initial patient satisfaction and overall success with rigid gas permeable contact lenses

BACKGROUND: Rigid gas permeable (RGP) contact lenses have numerous benefits; however, RGP lens use is not increasing in the United States. An important factor for this trend has been initial comfort. Studies have demonstrated that how RGPs are presented to patients, in addition to lens design, can play an important role in the initial comfort process. Another important factor could be the use of a topical anesthetic during the fitting and dispensing visits. The purpose of this study was to use a multicenter format to determine if topical anesthetic use increased the likelihood of patient satisfaction and success. METHODS: A total of 80 subjects, with no previous rigid lens wear experience, was entered into this 1-month study, including 20 subjects from each of 4 institutions. Subjects were randomly divided into the following two groups: (A) anesthetic or (B) placebo, with the former group receiving one drop of a topical anesthetic before lens insertion at both the diagnostic fitting and dispensing visits, whereas the latter group received a placebo. Subjects completed a questionnaire on their perception of rigid lens wear both immediately before fitting and at the 1-month visit. After diagnostic fitting with rigid lenses, subjects completed an adaptation questionnaire after 15 min, 1 week, 2 weeks, and 1 month of lens wear. RESULTS: Seventy of the 80 subjects completed the study and, of the 10 subjects who discontinued, 8 were in the placebo group. In all categories evaluated, the anesthetic group experienced a more optimum adaptation experience at each visit vs. the placebo group. Specifically, overall comfort was rated significantly higher at both dispensing and 2 weeks. In addition, the anesthetic group exhibited significantly greater overall satisfaction with rigid lens wear at 2 and 4 weeks. Also, the anesthetic group perceived their adaptation, sensitivity, and adaptation time to be significantly better at the 1-month visit. There was no significant difference in corneal staining between these two groups at each visit, with the exception of a greater amount of staining in the central quadrant for the placebo group at the 1-month visit. CONCLUSIONS: The use of a topical anesthetic at the fitting and dispensing visits for first-time wearers of RGP lenses resulted in significantly fewer dropouts, improved initial comfort, an enhanced perception of the adaptation process, and greater overall satisfaction after 1 month of lens wear as compared to the use of a nonanesthetizing placebo at those visits. This result, in combination with both presenting RGP lenses in a nonthreatening manner and optimizing the lens design and fitting relationship, should result in a positive adaptation process and successful wear of RGP contact lenses.     

Pulmonary alveolar proteinosis in a child: HRCT findings before and after bronchoalveolar lavage

We demonstrate the high-resolution computed tomography (HRCT) findings of pulmonary alveolar proteinosis in a child before and after bronchoalveolar lavage. The CT pattern in our case differs from the pattern described in previous reports. We found a more homogeneous distribution of the pulmonary changes and a "crazy paving" pattern. High-resolution CT may be helpful in the differential diagnosis of this rare disease and in the follow-up of the pulmonary changes after bronchoalveolar lavage.     

The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation

To compare the relative sensitivity and specificity of bone turnover indexes for bone loss or gain in early postmenopausal women, we performed a multicenter trial in 236 menopausal women (mean age, 51 yr), who were randomized to hormone replacement therapy (HRT) or calcium supplementation (CS; 500 mg/day) for 1 yr. Two markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase (BSAP), and two markers of bone resorption, urinary N-telopeptide (NTx) and urinary free deoxypyridinoline (fDpd), as well as spine and femoral neck bone mineral density (BMD) were measured at baseline and 3, 6, and 12 months after treatment. Women receiving HRT (n = 105) showed a significant increase in spine BMD (+2.5%; P < 0.0001) and hip BMD (+1.0%; P = 0.02) compared to women receiving CS, who showed a decline at both sites (-1.1%; P < 0.01). All four markers showed time-dependent decreases in women receiving HRT (P < 0.001) and no change in women receiving CS alone. When baseline indexes of turnover were stratified by quartile, there was a significantly greater increase in BMD among those with the highest NTx, OC, and BSAP levels compared to that in those with the lowest NTx, OC, and BSAP levels (P < 0.05). The highest quartile for percent change from baseline to 6 months in fDpd, BSAP, and NTx was also associated with the greatest change in spine BMD at 1 yr. Receiver operator characteristic curves for percent change from baseline to 6 months in an individual marker to 1 yr change in BMD during HRT revealed that the percent change in NTx provided the greatest discrimination between gain and loss of BMD. When subjects receiving HRT were compared by their positive or negative skeletal response at 1 yr and their baseline turnover marker, initial NTx values were significantly higher in those that gained bone than in those that lost bone (P = 0.0002). CS women in the highest quartile for NTx at baseline had significantly greater decreases in spine BMD than subjects with the lowest NTx values (P < 0.005), although this was not true for fDpd (P < 0.20). In conclusion, for early postmenopausal women there are differential responses of biochemical markers to HRT and CS. Baseline urinary NTx and serum OC were the most sensitive predictors of change in spine BMD after 1 yr of either HRT or CS. Similarly, the percent change in NTx and OC from baseline to 6 months best predicted bone gain or loss. We conclude that markers of bone formation and resorption can be used clinically to predict future BMD in early postmenopausal women.     

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.