Concurrent management of suppurative intracranial complications of sinusitis and acute otitis media in children.

OBJECTIVE: Intracranial complications of sinusitis and acute otitis media (AOM) are rare but life-threatening events. In children with suppurative intracranial complications, concurrent neurosurgical and otolaryngological (ORL) intervention has been recommended to optimize outcomes. The aim of this study was to investigate outcomes following concurrent neurosurgical and ORL intervention. METHODS: A retrospective cohort study of children undergoing neurosurgical intervention for intracranial complications of sinusitis or AOM in two neurosurgical centres in Ireland was conducted. RESULTS: 65 children were identified. Mean age was 11.9 years. The most prevalent symptoms were headache, pyrexia, altered level of consciousness, facial swelling, and vomiting. Subdural empyema (n = 24, 36.9%) and extradural abscess (n = 17, 26.2%) were the most common complications. 54 underwent same admission ORL intervention; 47 (87%) were performed concurrently or earlier. For rhinogenic infections, 35 (64.8%) underwent endoscopic sinus surgery (ESS), 13 (24.1%) underwent frontal sinus trephine, and 5 (9.3%) underwent maxillary sinus washout alone. For otogenic infections, 10 (90.9%) underwent mastoidectomy and 7 (63.6%) underwent tympanostomy tube placement. 19 (29.2%) had post-operative neurological deficits, of which 2 (3.1%) were permanent. Streptococcus intermedius was the most common pathogen (n = 30, 46.2%). Concurrent intervention reduced the prevalence of residual collection (p = 0.018) and the need for revision neurosurgical intervention (p = 0.039) for sinogenic complications. The same trends did not achieve statistical significance for the otogenic group. Mortality was 0%. CONCLUSION: Intracranial complications of sinusitis and AOM are best managed in a specialist centre with multidisciplinary input. Concurrent ORL and neurosurgical intervention reduces abscess recurrence and requirement for revision neurosurgery in sinogenic complications and should represent the standard of care. ESS is the ORL modality of choice in experienced hands.

Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia.

We have evaluated the hypolipidemic effects of mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis in 13 patients with heterozygous familial hypercholesterolemia (FH). Patients were maintained on a low-cholesterol diet and received sequentially increasing doses of 5, 10, 20, and 40 mg of mevinolin twice daily for a period of 1 mo on each dose. Plasma concentrations of low density lipoprotein cholesterol decreased by 19.8% on the 5 mg twice daily dose (P less than 0.05 vs. base line), 28.4% on 10 mg of mevinolin twice daily (P less than 0.05 vs. 5 mg twice daily), 35% on 20 mg of mevinolin twice daily (P less than 0.05 vs. 10 mg twice daily), and 37.7% on 40 mg of mevinolin twice daily (not statistically different from 20 mg twice daily). Concentrations of high density lipoprotein cholesterol remained stable on all doses of mevinolin whereas plasma triglyceride levels fell significantly on the 20 mg (-30.7%) and 40 mg (-34.3%) twice daily doses of mevinolin. Mevinolin was well tolerated and all patients completed the study period. Side effects during the period of study were limited to transient insomnia and headaches in two patients, transient increases in alkaline phosphatase in three patients, and a modest but sustained increase in alkaline phosphatase in a fourth patient. These results indicate that mevinolin is an effective hypolipidemic agent in patients with heterozygous FH but that the optimal doses in these patients are greater than those previously reported in normal volunteers. If long-term safety can be satisfactorily established, mevinolin offers considerable promise in the therapy of heterozygous FH.

Asynchronous regional brain volume losses in presymptomatic to moderate AD.

To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled in a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 --> 0), Very Mild (CDR 0 --> 0.5 and 0.5 --> 0.5), Mild (CDR 0.5 --> 1.0 and 1.0 --> 1.0) and Moderate (CDR 1.0 --> 2.0 and 2.0 --> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p<0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia.

Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence.

The sequence of chemotherapy administered prior to cranial irradiation rather than the more traditional order of radiation followed by chemotherapy is currently being evaluated. This rodent study was designed to assess the sequencing of radiation therapy and chemotherapy administered with osmotic blood-brain barrier disruption (BBBD). Drug delivery and acute toxicity were evaluated. Two clinically relevant chemotherapy regimens were given with BBBD: intraarterial methotrexate (MTX, 1 g/m2), or a combination of intraarterial carboplatin (200 mg/m2) and i.v. etoposide (200 mg/m2). In a randomized protocol, the standard rodent model of 2000 cGy as a single fraction using parallel opposed portals was administered 30 days prior to, concurrent with (24 h prior), or 30 days after these two chemotherapeutic regimens. A total of 72 animals was evaluated in this study. The administration of external beam radiation therapy either prior to or concurrent with the administration of a high molecular weight marker 14C-labeled dextran 70 (Mr 70,000), or a low molecular weight marker 3H-labeled MTX (Mr 456) resulted in a statistically significant (P < 0.01) decrease in drug delivery when compared to animals not receiving cranial irradiation. Seizures were observed in 26% of the animals that received radiation prior to the administration of intraarterial MTX after BBBD. It did not matter whether the radiotherapy was administered 30 days prior to or concurrent with MTX. Seizures were not seen in any other group. The mortality in animals receiving radiotherapy 30 days prior to chemotherapy was significantly (P = 0.03) higher than the mortality in control animals receiving chemotherapy after osmotic BBBD, but no radiation. Drug delivery was significantly decreased when the animals received prior radiotherapy; the administration of radiation prior to MTX with BBBD resulted in an increased incidence of seizures, and there was a significant increase in mortality when cranial irradiation was given 30 days prior to chemotherapy administered with BBBD. With regard to delivery and toxicity, chemotherapy with BBBD administered prior to radiotherapy may have advantages over the other sequences utilizing chemotherapy and cranial irradiation.

Differential permeability of a human brain tumor xenograft in the nude rat: impact of tumor size and method of administration on optimizing delivery of biologically diverse agents.

To assess how to maximize drug delivery to intracerebral tumors and surrounding brain, this study examined the effects of route and method of administration and tumor size on the distribution of three agents in a nude rat intracerebral tumor xenograft model. Aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), and dextran 70 (M(r) 70,000) were administered i.v. or intra-arterially (i.a.) with or without osmotic blood-brain barrier disruption (BBBD) at 8, 12, or 16 days after tumor cell inoculation (n = 72). A 2.2- to 2.5-fold increase in delivery to tumor and surrounding brain was observed when i.a. was compared with i.v., and a 2.5- to 7.6-fold increase was observed when BBBD was compared with the saline control. The combined effect of i.a. administration and BBBD was to increase delivery 6.3-16.7-fold. The greatest benefit of BBBD was seen in animals with 8-day tumors, whereas BBBD had less benefit in improving delivery to intracerebral tumor and brain around tumor as the tumors grew larger. Regional delivery decreased as the molecular weight of the agent increased. Based on these results, we suggest that i.a. administration of antitumor agents may be adequate to obtain initial responses in large, very permeable, intracerebral tumors. However, in smaller, less permeable tumors or after an initial response to treatment, there may be a significant therapeutic advantage to i.a. agent administration and BBBD.

Beta-carotene in HIV infection: an extended evaluation.

OBJECTIVE: Several small short-term intervention studies have suggested that beta-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether beta-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period. METHODS: HIV-positive patients were randomly assigned to receive either 60 mg beta-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, beta-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit. RESULTS: Seventy-two patients signed informed consent forms and entered the study. Except for serum beta-carotene concentration, there were no statistically significant differences (P < 0.05) between the treatment (60 mg beta-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment. DISCUSSION: Earlier studies suggesting that beta-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of beta-carotene for HIV-infected patients.

Effects of naloxone infusions on pulsatile thyrotropin secretion.

Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 vs. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 vs. 9.17 +/- 1.36 mU/L). Serum T3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge.

Incorporation of dietary n-3 fatty acids into the fatty acids of human adipose tissue and plasma lipid classes.

The consumption of n-3 fatty acids from seafood has been related to a lower incidence of coronary artery disease. Adipose tissue composition has served as a biological marker of chronic ingestion of many dietary polyunsaturated fatty acids. However, the incorporation of n-3 fatty acids into the fat depots has not been studied in humans. Daily dietary supplementation with > or = 10 g n-3 fatty acids from fish oil for > 12 mo resulted in significantly greater 20:5n-3, 22:5n-3, and 22:6n-3 concentrations in fatty acids of adipose tissue, and a greater 20: 5n-3 fatty acid content in plasma lipid classes (cholesterol esters, phospholipids, and free fatty acids) of supplemented subjects compared with nonsupplemented control subjects. Combined values for all subjects indicated that fatty acid concentrations of n-3 plasma lipid classes, including 20:5n-3, 22:5n-3, 22:6n-3, and total n-3, significantly correlated with corresponding concentrations of fatty acids in adipose tissue. These findings indicate that the long-term ingestion of large amounts of n-3 fatty acids in humans resulted in their incorporation into the adipose tissue fatty acids. Incorporation of the fatty acids into adipose tissue warrants consideration for use in clinical studies requiring precise documentation of long-term n-3 fatty acid consumption.

Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.

BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.

Motor slowing precedes cognitive impairment in the oldest old.

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

Persistent inflammatory response in stroke survivors.

OBJECTIVE: Goals were to determine how long acute-phase markers remain elevated after ischemic stroke and how marker levels relate to stroke risk factors, stroke mechanism, and subsequent vascular events. METHODS: Fibrinogen (FIB), C-reactive protein (CRP), leukocytes (WBC), neutrophils (PMN), interleukin-6, and interleukin-1 receptor antagonist were measured at stroke onset and at 6 weeks, 6 months, and 1 year after enrollment, or until a vascular event occurred in 136 acute ischemic stroke patients, 76 patients with comparable risk factors for stroke, and 48 age-balanced healthy subjects. RESULTS: Multivariate logistic analysis showed that prior stroke and FIB level predicted new events in stroke patients (p < 0.04 for both), whereas congestive heart failure (p < 0.02) and creatinine level (p < 0.006) were predictive in at-risk patients. After controlling for infection, FIB, CRP, and PMN levels at baseline were higher in at-risk but not in stroke patients with recurrent events (p < 0.05 for all). At 1 year, FIB levels remained elevated in event-free stroke survivors compared with levels in the risk and control groups (p < 0.001 for both). FIB also remained higher in stroke survivors who had atheroembolism (AE) compared with non-AE stroke survivors (381+/-72 versus 342+/-78 mg/dL, p < 0.02). Peripheral vascular disease was an independent predictor (p < 0.0001) of longitudinal FIB in stroke survivors. Of note, both WBC and PMN levels were chronically elevated in patients with stroke risk factors and in stroke survivors (p < 0.0001 for both) compared with healthy elderly subjects. CONCLUSIONS: Most acute-phase markers decline gradually after stroke, but FIB remains significantly elevated and is associated with increased risk for recurrent vascular events.

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia.

OBJECTIVE: To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. BACKGROUND: Postmortem studies suggest that the earliest changes in Alzheimer's disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. METHODS: 30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. RESULTS: NoD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NoD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. CONCLUSIONS: Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Brain volume preserved in healthy elderly through the eleventh decade.

OBJECTIVE: To determine which brain regions lose volume with aging over time in healthy, nondemented elderly. BACKGROUND: Cross-sectional studies suggest widespread loss of brain volume with aging. These studies may be biased by significant numbers of preclinically demented elderly in the oldest comparison groups. Longitudinal studies may allow closer determination of the effect of aging unaffected by dementia. METHODS: Quantitative volumetric MRI was performed annually on 46 healthy subjects older than age 65 who had maintained cognitive health a mean of 5 years. Comparisons (analysis of variance) were made of rates of volume loss (slopes) divided into 11 young-old (mean age, 70 years), 15 middle-old (mean age, 81 years), and 20 oldest-old (mean age, 87 years) subjects. Regions of interest included CSF spaces, lobar regions, and limbic-subcortical regions. RESULTS: There were significant differences between groups in intracranial, total brain, left hemisphere, right hemisphere, temporal lobe, basilar-subcortical region, and hippocampus volumes, with oldest-old subjects showing the smallest volumes, followed by middle-old and young-old subjects. Oldest-old subjects had significantly greater subarachnoid volumes than the younger groups. There were no significant differences in rates of change of regions of interest across age groups. CONCLUSIONS: After age 65 there is minimal brain volume loss observed over time in healthy elderly. Brain volume differences seen cross-sectionally, at any age, likely reflect small, constant rates of volume loss with healthy aging. Healthy oldest-old subjects do not show greater rates of brain loss compared with younger elderly, suggesting that large changes seen in cross-sectional studies reflect the presence of preclinical dementia in older groups.

Parkinson's disease, CYP2D6 polymorphism, and age.

OBJECTIVE: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. METHODS: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. RESULTS: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset PD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 at mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. CONCLUSION: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect.

Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease.

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.

Comparative hypolipidemic effects of lovastatin and simvastatin in patients with heterozygous familial hypercholesterolemia.

We have compared the effects of lovastatin and simvastatin on plasma lipoproteins, fibrinogen and urinary mevalonic acid excretion in twenty-three patients with heterozygous familial hypercholesterolemia. After a baseline period patients were randomly assigned to receive lovastatin or simvastatin at doses of 10, 20 and 40 mg twice daily, for a period of 2 months each, and then, after a 4-week wash-out period, all patients received the alternate drug for a similar period of therapy. Both drugs were well-tolerated and no patients were withdrawn due to side effects. Lipid values returned to baseline after discontinuation of therapy and no carry-over effect was observed. Treatment with lovastatin resulted in decreases in LDL cholesterol concentrations from 274 mg/dl at baseline to 211, 192 and 178 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Treatment with simvastatin reduced concentrations of LDL cholesterol to 194, 168 and 156 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Concentrations of HDL cholesterol increased on both drugs, but no dose response relationship was apparent. Both drugs reduced the 24-h urinary excretion of mevalonic acid, an intermediate in cholesterol biosynthesis, but the magnitude of decrease was similar with lovastatin and simvastatin. Small, but statistically non-significant decreases in fibrinogen occurred with both drugs. Patients who showed the greatest hypolipidemic effect during treatment with lovastatin also showed an excellent therapeutic response to simvastatin and vice versa. We conclude that, on a milligram per milligram basis, simvastatin is twice as potent as lovastatin in the treatment of familial hypercholesterolemia and that with both drugs, reductions in LDL cholesterol concentrations are accompanied by decreases in the urinary excretion of mevalonic acid.

Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.

Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives.

PIP: This study was conducted to test the hypothesis that hyperhomocyst(e)inemia may be an additional risk factor for vascular occlusions in women taking oral contraceptives (OCs). A total of 200 women who were regular users of OC tablets containing 30 or 50 mcg ethinyl estradiol were studied: 100 were controls and 100 had documented vascular occlusion. Serum levels of homocyst(e)ine and anti-estrogen antibody were determined under blind conditions. These were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine and anti-estrogen antibodies when compared to controls. They were also older and frequent smokers. The variables investigated--namely, anti-estrogen antibody, age-adjusted log, transformed homocyst(e)ine, age, and smoking--were independent predictors of vascular occlusions when considered in isolation. Moreover, a model assessing these variables and their interactions, indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted log and homocyst(e)ine. The study suggests that these variables can identify women at risk, and the determination of anti-estrogen antibody and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking OCs.

Ciprofibrate in the therapy of type II hypercholesterolemia. A double-blind trial.

The hypolipidemic efficacy of ciprofibrate was evaluated in patients with type II hypercholesterolemia. Patients were randomized to placebo or ciprofibrate (50 mg or 100 mg/day) and, after a 6-week baseline period, received medication for a period of 12 weeks. Blood samples were analyzed every 2 weeks. Twenty patients completed the study (4 on placebo, 7 on 50 mg/day, and 9 on 100 mg/day ciprofibrate). The drug was well tolerated in all patients. Lipid values in the patients on active drug decreased and attained stable values after 4 weeks of treatment. Compared to baseline values, total and LDL cholesterol decreased 11% and 13% on the 50-mg dose whereas HDL increased 8%. Plasma triglyceride fell by 22%. In patients receiving 100 mg ciprofibrate, total and LDL cholesterol fell by 20% (334 leads to 269 mg/dl) and 24% (262 leads to 198 mg/dl), respectively. HDL increased 9.8% (51 leads to 56 mg/dl) and triglyceride decreased by 30% (102 leads to 69 mg/dl). Values in the placebo group remained stable. We conclude that once daily therapy with 100 mg ciprofibrate, is effective in reducing LDL levels in patients with type II hypercholesterolemia (mainly heterozygous FH) and that this decrease is paralleled by small rises in HDL.

Premenopausal black women have more risk factors for coronary heart disease than white women.

Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 +/- 9.2 vs 29.0 +/- 9.4 kg/m2, p = 0.021), and higher systolic (124 +/- 17 vs 115 +/- 14 mm Hg, p <0.0001) and diastolic (79 +/- 14 vs 75 +/- 11 mm Hg, p = 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 +/- 31.3 mg/dl) than in the white women (19.2 +/- 23.7 mg/dl, p <0.0001). The plasma total homocysteine level was also higher in the black women (8.80 +/- 3.38 vs 7.81 +/- 2.58 micromol/L, p = 0.013). The black women, however, had lower plasma triglyceride levels (0.91 +/- 0.46 vs 1.22 +/- 0.60 mmol/L, p <0.0001), and a trend toward higher high-density lipoprotein (HDL) cholesterol levels (1.37 +/- 0.34 vs 1.29 +/- 0.31 mmol/L, p = 0.064) than the white women. Plasma total and low-density lipoprotein (LDL) cholesterol levels were similar, despite a greater consumption of saturated fat and cholesterol by the black women. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, premenopausal black women had a higher mean body mass index, blood pressure, lipoprotein(a), and plasma total homocysteine level, and a greater consumption of saturated fat and cholesterol than white women. These differences in coronary risk factors may place the black women in our study at increased risk for CHD compared with the white women.