Under-reporting of notifiable infectious disease hospitalizations: significant improvements in the Irish context.

Notification of infectious disease is essential for prompt public health action and epidemiological analysis. The aim of this study was to compare national hospitalization data to national notification data in order to assess if there was significant under-reporting of hospitalized notifiable infectious diseases in recent years in Ireland. All in-patient discharges from public hospitals in the Republic of Ireland from 2006 to 2011 with a principal diagnosis of a notifiable disease were compared with national notification data. It was found that only a potential 1·8% of extra notifications could have arisen due to these hospitalization events and would represent a tenfold reduction on a previous estimate of under-reporting in the Irish context. Viral meningitis, viral encephalitis, bacterial meningitis not otherwise specified and malaria were the most common diseases for which there were more hospitalizations than notifications reported. The results of this study support the conclusion that the reduction in under-reporting can mainly be accounted for by the introduction of laboratories as notifiers in conjunction with the roll out of the Computerized Infectious Disease Reporting system (CIDR). However, for the diseases highlighted, the notification data underestimates the true burden of disease and this has implications for understanding the epidemiology of these diseases.

Diversity in prevalent PCR ribotypes of clinical strains of C. difficile.

In 2009, a programme of Clostridium difficile ribotyping was established in the north east. The aim of this project was to profile circulating ribotypes in the region, In all, 50 notified north east Clostridium difficile cases were ribotyped. The majority of cases occurred in patients over 70 years and in hospital in-patients. The most common ribotype identified was 027 (n = 12, 24%) and 005 (n = 8, 16%). Ribotype 078 was also detected (n = 5, 10%). Comparison with a 2009 national ribotyping study demonstrated that there were a number of ribotypes identified in the north east that were not identified during the national study and visa versa. The results of this study point to the existence of regional variation in circulating Clostridium difficile strains in Ireland. A reference facility for Ireland is urgently required to provide a central point for enhanced testing and epidemiological analysis of national and regional Clostridium difficile trends.

A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.

AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.

Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

Admissions and costs to acute hospitals resulting from road traffic crashes, 2005-2009.

Road traffic crashes (RTCs) remain a leading cause of death and injury. The aim of this study was to explore the use of hospital data as a source of RTC-related injury data in Ireland, as current systems are believed to under-estimate the burden. Information on inpatient discharges for years 2005-2009, admitted with RTC-related injuries were extracted from HIPE. There were 14,861 discharges; 9,661 (65.0%) were male, with an average age of 33 years. The median length of stay was two days. The most common diagnosis was head injury (n = 4,644; 31.2%). The average inpatient hospital cost was Euro 6,395 per discharge. 1,498 (10.1%) were admitted to intensive care units. This study has identified 3.5 times more serious injuries (14,861) than identified in the Road Safety Authority (RSA) statistics (4,263) indicating that the extent of road injuries is greater than previously estimated. Hospital data could be used annually in conjunction with RSA and other data; ideally the data should be linked.

General practice out-of-hours service in Ireland provides a new source of syndromic surveillance data on influenza.

The use of routinely available electronic sources of healthcare data on the spread of influenza has the potential to enhance current surveillance activities. This study aimed to develop a method for identifying influenza-related records from general practitioner(GP) out-of-hours (OOH) services in Ireland. Data from one such service were interrogated for keywords relating to influenza-like illness (ILI) and a proxy measure of influenza activity in the community setting was developed. Comparison of this syndromic surveillance measure with national data on ILI consultation rates demonstrated a statistically significant temporal correlation.In five out of six influenza seasons investigated,peaks in the GP OOH influenza-related calls appeared at least one week ahead of peaks in the national ILI consultation rates. The method described in this paper has been extended to nine OOH services in Ireland (covering 70% of the Irish population) to provide weekly figures on self-reported illness for influenza in the community and its data have been incorporated into the national weekly influenza reports produced by the Health Protection Surveillance Centre. These data should provide early warnings of both seasonal and pandemic influenza in Ireland.

Alcohol levels in killed drivers and pedestrians on Irish roads 2003-2005: a national study.

No official data are provided in Ireland to indicate what proportion of the deaths on Irish roads have alcohol as a contributory factor. The aim of this study was to identify the blood alcohol concentration (BAC) in fatally injured drivers and pedestrians in Ireland. An Garda Síochána (The Irish police) gather data on all fatal road crashes and individual paper files are kept on each crash. The authors examined all such files for deaths in 2003-2005. Of the 611 drivers fatally injured, 184 (30.1%) were over the BAC legal limit (80 mg/100 ml). BACs were available for only 397 (64.9%) of drivers. Of the 397 drivers who had their BACs recorded, 184 (46.3%) had a BAC over the legal limit of 80 mg/100 ml and 220 (55.4%) had BACs 20 mg/100 ml or higher. Fatally injured drivers with BACs 20 mg/100 ml or greater were more likely to be male (88.6%/o, p<0.01). Alcohol-related crashes were more likely to occur on week end nights. Pedestrian alcohol consumption was considered to be a contributory factor in 50 (24.4%) of the pedestrian deaths with 22 (10.7%) of the pedestrians having alcohol levels exceeding 240 mgl/100 ml. This study confirms that alcohol is a significant factor in road deaths. Further targeted action including a reduction in the legal limit is required.

The impact of legislation in Ireland on handheld mobile phone use by drivers.

Under the Road Traffic Act, 2006 handheld mobile phone use whilst driving is an offence liable to a fine and penalty points. The aim of this study was to determine whether there has been a change in driver behaviour following the introduction of this legislation. This study found that 2.3% of drivers were still using a handheld mobile phone.

Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects.

This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL). Subjects homozygous for E3 converted approximately 50% of LVDL2 to LDL, the remainder being lost by direct catabolism. Those with the E2 phenotype produced less VLDL1, but converted more of it to VLDL2 (compared to E3 subjects). They displayed a characteristic dyslipidemia with the presence of slowly catabolized VLDL1 and VLDL2 remnants. LDL levels were low owing to increased direct catabolism of VLDL2 and IDL and a reduced efficiency of delipidation; only 25% of VLDL2 apo B was directed to LDL production. In contrast, E4 subjects converted more VLDL2 apo B to LDL than E3 subjects. About 70% of VLDL2 apo B was found in LDL; direct catabolism of VLDL and IDL was reduced as was the fractional catabolic rate of LDL (0.2 vs. 0.26 in E3 subjects). These changes in the VLDL----IDL----LDL metabolic cascade can in part be explained by alterations in hepatic LDL receptors with E2 subjects having higher and E4 subjects lower activities than those in E3 homozygotes.

Blood alcohol levels in persons who died from accidents and suicide.

Although it is known that alcohol is associated with a high proportion of fatal accidents and suicides, little information is available in Ireland on blood alcohol concentrations (BACs) of those who died. This study was undertaken to identity the (BACs) in persons who died as a result of suicide or injury. The study was a retrospective review of coroners' records to identify BACs in three counties in Ireland. All cases where the person died as a result of injury or suicide in 2001 and 2002 were included. There were 129 deaths eligible for inclusion. Of these, 98 (76%) were male, 55 (42.6%) were road traffic accidents (RTAs), 31 (24.0%) suicides, 12 (9.3%) substance misuse, 11 (8.5%) house fires and 20 (15.5%) others. Of the 55 who died as a result of RTAs, 22 (40%) had positive BACs ranging from 16mg/100 ml to 325 mg/100 ml. Of the 31 who died as a result of suicide, 28 (90.3%) were male. BACs were available for 29 (93.5%). Of these, 16 (55.5%) had alcohol detected. Persons aged less than 30 years were more likely to have alcohol in their blood (p < 0.002). The mean BAC for persons aged less than 30 was 191.5 mg/100 ml compared to 84.0 mg/100 ml for those aged 30 and over. The mean BAC for adults who died in house fires was 225.2 mg/100 ml. The high BACs in those who died as a result of suicide or injury reflect the high level of alcohol consumption and binge drinking in Ireland.

Characteristics of women seeking emergency contraception in general practice.

The aim of this study was to profile the users of emergency contraception (EC) attending general practices and a general practice out-of-hours co-operative service using a pre-piloted questionnaire. Questionnaires were offered to 171 women and completed by 144 (84.2%). Mean age was 24.4 years (Standard Deviation = 6.7, range 14 to 51). Most were single, 116 (80.6%). Those who had no regular partner at the time of seeking EC were more likely to have > or =6 lifetime sexual partners than those in stable relationships (OR: 3.5; CI: 1.14-10.86, p < 0.03). At the time of seeking EC 121 (84.0%) were using some method of contraception. Ninety-three (64.6%) presented within 24 hours of sexual intercourse. Concerns about condoms were the commonest reason for seeking EC. For 55 (38.2%) this was their first time to use EC. Thirty-three (22.9%) were drunk at the time of intercourse.

GP supply, deprivation and emergency admission to hospital for COPD and diabetes complications in counties across Ireland: an exploratory analysis.

INTRODUCTION: Geographical variation in rates of emergency inpatient admission for chronic disease may be due to variation in health need. However, it may also reflect differences in the provision of services which reduce the risk of inpatient admission for chronic disease, such as primary care. AIMS: The aim of this paper was to examine the effect of primary care provision [general practitioner (GP) supply] and deprivation on county-specific rates of emergency admission to hospital for diabetes complications and chronic obstructive pulmonary disease (COPD) in Ireland. METHODS: Data on emergency inpatient discharges were obtained from the hospital inpatient enquiry (HIPE) system. Secondary data on GP supply were obtained from a recently published study, while secondary data on deprivation were obtained from the Small Area Health Research Unit. The effect of county-level GP supply and deprivation on age-standardised rates of discharge for diabetes complications and COPD were examined, adjusting for population density and the proportion of the population who were eligible for free primary care. RESULTS: Greater deprivation and lower GP supply are associated with increased rates of discharge from hospital for COPD and diabetes complications. However, these associations are stronger in counties where a lower proportion of the population are eligible for free primary care. CONCLUSION: Geographical variation in rates of admission to hospital for chronic disease is associated with both population need and health system factors. These findings suggest that primary care resourcing must be a key consideration in any efforts to tackle acute hospital capacity problems.

Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects.

The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after an overnight fast (control study, n = 8), during inhibition of lipolysis with an antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic-hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was used to derive the kinetic constants. The mean rate of VLDL1 apo B production was 708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day (NS) during the acipimox study. Mean VLDL2 apo B production was significantly increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS). The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three studies. We conclude that acute lowering of FFAs does not change the overall production rate of VLDL particles, but there is a shift toward production of smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles secreted remained constant. Insulin acutely suppresses the total production rate of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1 particles. Based on these findings, we postulate that insulin has a direct suppressive effect on the production of VLDL apo B in the liver, independent of the availability of FFAs.

A functional chimeric modular polyketide synthase generated via domain replacement.

BACKGROUND: Modular polyketide synthases (PKSs), such as 6-deoxyerythronolide B synthase (DEBS), are large multifunctional enzymes that catalyze the biosynthesis of structurally complex and medically important natural products. Active sites within these assemblies are organized into 'modules', such that each module catalyzes the stereospecific addition of a new monomer onto a growing polyketide chain and also sets the reduction level of the beta-carbon atom of the resulting intermediate. The core of each module is made up of a 'reductive segment', which includes all, some, or none of a set of ketoreductase (KR), dehydratase, and enoylreductase domains, in addition to a large interdomain region which lacks overt function but may contribute to structural stability and inter-domain dynamics within modules. The highly conserved organization of reductive segments within modules suggests that they might be able to function in unnatural contexts to generate novel organic molecules. RESULTS: To investigate domain substitution as a method for altering PKS function, a chimeric enzyme was engineered. Using a bimodular derivative of DEBS (DEBS1+TE), the reductive segment of module 2, which includes a functional KR, was replaced with its homolog from module 3 of DEBS, which contains a (naturally occurring) nonfunctional KR. A recombinant strain expressing the chimeric gene produced the predicted ketolactone with a yield (35 %) comparable to that of a control strain in which the KR2 domain was retained but mutationally inactivated. CONCLUSIONS: These results demonstrate considerable structural tolerance within an important segment found in virtually every PKS module. The domain boundaries defined here could be exploited for the construction of numerous loss-of-function and possibly even gain-of-function mutants within this remarkable family of multifunctional enzymes.

The granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tü22: sequence analysis and expression in a heterologous host.

BACKGROUND: The granaticins are members of the benzoisochromanequinone class of aromatic polyketides, the best known member of which is actinorhodin made by Streptomyces coelicolor A3(2). Genetic analysis of this class of compounds has played a major role in the development of hypotheses about the way in which aromatic polyketide synthases (PKSs) control product structure. Although the granaticin nascent polyketide is identical to that of actinorhodin, post-PKS steps involve different pyran-ring stereochemistry and glycosylation. Comparison of the complete gene clusters for the two metabolites is therefore of great interest. RESULTS: The entire granaticin gene cluster (the gra cluster) from Streptomyces violaceoruber T-22 was cloned on either of two overlapping cosmids and expressed in the heterologous host, Streptomyces coelicolor A3(2), strain CH999. Chemical analysis of the recombinant strains demonstrated production of granaticin, granaticin B, dihydrogranaticin and dihydrogranaticin B, which are the four known metabolites of S. violaceoruber. Analysis of the complete 39,250 base pair sequence of the insert of one of the cosmids, pOJ466-22-24, revealed 37 complete open reading frames (ORFs), 15 of which resemble ORFs from the act (actinorhodin) gene cluster of S. coelicolor A3(2). Among the rest, nine resemble ORFs potentially involved in deoxysugar metabolism from Streptomyces spp. and other bacteria, and six resemble regulatory ORFs. CONCLUSIONS: On the basis of these resemblances, putative functional assignments of the products of most of the newly discovered ORFs were made, including those of genes involved in the PKS and tailoring steps in the biosynthesis of the granaticin aglycone, steps in the deoxy sugar pathway, and putative regulatory and export functions.

Factors associated with self-reported depression and self-esteem among school-going adolescents from a geographically defined region in Ireland.

BACKGROUND: Recent reviews indicate that mental health problems in the young are increasing. AIMS: To measure the prevalence of, and risk factors associated with, depression and low self-esteem among Irish post-primary students. METHOD: 1,428 students, randomly selected from a sample of post-primary schools, were given an anonymised questionnaire. Analyses included bivariate and multivariate logistic regression. RESULTS: Questionnaires were completed by 992 (69.9%) respondents. 206 (20.8%) had a high depression score. Being from a single parent family (OR 2.8, 95% CI 1.5-5.4, p<0.001); having low self esteem (OR 13.44 95% CI 8.9-20.3, p<0.001); being female (OR, 3.7, 95% CI 2.5-5.6 p<0.001) and having a low fitness level (OR 1.8, 95% CI 1.2-2.8 p<0.006) were independently associated with a high depression score. CONCLUSIONS: The level of self-reported depression was high among these respondents and risk factors identified include having low self-esteem, being female, being from a single parent family and having a low fitness level.

The use of hand held mobile phones by drivers.

The use of mobile phones by drivers has been shown to be associated with an increased risk of motor vehicle crashes. The aim of this study was to identify the use of hand held mobiles phones by drivers in Ireland. Their use was investigated by a direct observation survey of drivers. The study showed that 3.6% of drivers were using hand held mobile phones while driving. This rate is high compared to other studies. Van drivers were three times more likely than other drivers to use a mobile phone whilst driving. Legislation needs to be introduced to ban their use and thereby reduce the risk of crashes.

Characterization of a gene conferring bialaphos resistance in Streptomyces coelicolor A3(2).

A gene (bar) was identified adjacent to the hrdD sigma factor gene in Streptomyces coelicolor A3(2). The predicted bar product showed 32.2% and 30.4% identity to those of the pat and bar genes of the bialaphos (Bp) producers Streptomyces viridochromogenes and Streptomyces hygroscopicus, respectively; these genes encode phosphinothricin (PPT) N-acetyltransferases that function as enzymes in the Bp biosynthetic pathway and as resistance determinants. The S. coelicolor bar gene conferred high-level resistance to Bp when cloned in S. coelicolor on a high-copy-number vector. Enzymic assay showed that the S. coelicolor bar gene product inactivates PPT by transfer of acetyl groups from acetyl CoA. The S. coelicolor bar gene appears to be expressed from two promoters (p1 and p2) and is divergently transcribed with respect to hrdD. The downstream (barp2) transcript overlaps the hrdDp1 transcript and the upstream (barp1) transcript overlaps both the hrdDp1 and hrdDp2 transcripts. Inactivation of hrdD did not prevent transcription from either bar promoter, indicating that sigma hrdD is not essential for recognition of these sequences.

The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects.

BACKGROUND: Cafestol is a diterpene in unfiltered coffee that raises plasma triacylglycerol in humans. OBJECTIVE: We studied whether cafestol increases plasma triacylglycerol by increasing the production rate or by decreasing the fractional catabolic rate of VLDL(1) [Svedberg flotation unit (S(f)) 60-400] apolipoprotein (apo) B. In addition, we studied the effect of cafestol on the composition of VLDL(1) and VLDL(2) (S(f) 20-60). DESIGN: Eight healthy normolipidemic men were administered a daily dose of 75 mg cafestol for 2 wk. A bolus injection of 7 mg L-[5,5,5-(2)H(3)]leucine/kg body wt was given after a baseline period with no cafestol and again after treatment with cafestol. We derived kinetic constants to describe the metabolism of VLDL(1) apo B by using a multicompartmental model. RESULTS: Cafestol significantly increased plasma triacylglycerol by 31% or 0.32 mmol/L (95% CI: 0.03, 0.61); the increase was due mainly to a nonsignificant rise in VLDL(1) triacylglycerol of 57% or 0.23 mmol/L (95% CI: -0.02, 0.48). Cafestol significantly increased the mean rate of VLDL(1) apo B production by 80% or 755 mg/d (95% CI: 0.2, 5353), whereas it did not significantly change the mean fractional catabolic rate of VLDL(1) apo B (mean increase of 3 pools/d; 95% CI: -4, 10]). Cafestol did not change the composition of VLDL(1). A significant increase in the ratio of VLDL(2) cholesteryl ester to triacylglycerol indicates that VLDL(2) became enriched with cholesteryl esters at the cost of triacylglycerol. CONCLUSION: Cafestol increases plasma triacylglycerol by increasing the production rate of VLDL(1) apo B, probably via increased assembly of VLDL(1) in the liver.

Effect of heparin-stimulated plasma lipolytic activity on VLDL APO B subclass metabolism in normal subjects.

Heparin given intravenously enhances lipolysis, although fasting lipids are not markedly altered in long-term administration. In the present study we investigated heparin-induced acute perturbation of VLDL subclass metabolism. Eight men were examined during a control study and during an 8.5 h infusion of heparin. 2H3-leucine was used as tracer and kinetic constants derived using a non-steady-state model. Heparin infusion increased both plasma lipoprotein and hepatic lipase activity and raised plasma FFAs two-fold (P < 0.001). The fractional catabolic rate (FCR) of VLDL1 apo B increased on heparin (25.7 +/- 4.2 and 10.8 +/- 1.7 pools/d, heparin vs. control, P < 0.02). The FCR of VLDL2 apo B increased to 12.6 +/- 1.9 pools/d on heparin vs. 8.8 +/- 1.1 pools/d during the control (NS). Total VLDL apo B production was not significantly changed (824 +/- 45 and 692 +/- 91 mg/d, heparin vs. control, NS). We conclude that during heparin infusion, the catabolism of especially large triglyceride-rich VLDL1 apo B is greatly increased. However, although the FFA levels were high during the heparin study, the production of total VLDL apo B did not rise. These findings are consistent with the known action of heparin on lipoprotein lipase but indicate that acute increase in plasma FFA levels does not lead to a rise in VLDL apo B production.