Doxycycline compared with prednisolone therapy for patients with bullous pemphigoid: cost-effectiveness analysis of the BLISTER trial.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disorder associated with significant morbidity and mortality. Doxycycline and prednisolone to treat bullous pemphigoid were compared within a randomized controlled trial (RCT). OBJECTIVES: To compare the cost-effectiveness of doxycycline-initiated and prednisolone-initiated treatment for patients with BP. METHODS: Quality-of-life (EuroQoL-5D-3L) and resource data were collected as part of the BLISTER trial: a multicentre, parallel-group, investigator-blinded RCT. Within-trial analysis was performed using bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, informing a probabilistic assessment of incremental treatment cost-effectiveness from a health service perspective. RESULTS: In the base case, there was no robust difference in costs or QALYs per patient at 1 year comparing doxycycline- with prednisolone-initiated therapy [net cost £959, 95% confidence interval (CI) -£24 to £1941; net QALYs -0·024, 95% CI -0·088 to 0·041]. However, the findings varied by baseline blister severity. For patients with mild or moderate blistering (≤ 30 blisters) net costs and outcomes were similar. For patients with severe blistering (> 30 blisters) net costs were higher (£2558, 95% CI -£82 to £5198) and quality of life poorer (-0·090 QALYs, 95% CI -0·22 to 0·042) for patients starting on doxycycline. The probability that doxycycline would be cost-effective for those with severe pemphigoid was 1·5% at a willingness to pay of £20 000 per QALY. CONCLUSIONS: Consistently with the clinical findings of the BLISTER trial, patients with mild or moderate blistering should receive treatment guided by the safety and effectiveness of the drugs and patient preference - neither strategy is clearly a preferred use of National Health Service resources. However, prednisolone-initiated treatment may be more cost-effective for patients with severe blistering.

Pathogenesis of bladder calculi in the presence of urinary stasis.

PURPOSE: Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. MATERIALS AND METHODS: Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. RESULTS: Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). CONCLUSIONS: In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.

Metastatic potential of a renal mass according to original tumour size at presentation.

OBJECTIVE: To determine the metastatic potential of renal masses based on original tumour size. MATERIALS AND METHODS: We identified 2651 patients who had undergone surgical resection for a unilateral, sporadic renal tumour between 1990 and 2006. Associations of tumour size with synchronous metastasis at presentation [M1 renal cell carcinoma (RCC)] and development of metastases, death from RCC, and death from any cause after surgery were evaluated using logistic and Cox proportional hazards regression. RESULTS: Of the 2651 patients studied, 182 (6.9%) presented with M1 RCC. Tumour size was significantly greater in patients with M1 RCC than in patients with M0 RCC (a median size of 10 vs 4.5 cm; P < 0.001). Only 1 of the 629 patients (0.2%) with a tumour <3 cm had M1 RCC and that tumour was 2.5 cm. The risk of M1 RCC increased from 1.1% for patients with tumours 3-3.9 cm to 16.5% for patients with tumours ≥7 cm. Of the 2124 patients with M0 RCC, 430 developed distant metastases at a median (range) of 1.4 (0.1-16.2) years after surgery. Only 9 of the 498 patients (1.8%) with a tumour <3 cm developed distant metastases after surgery. Each 1-cm increase in tumour size increased the risk of death from RCC by 20%[hazard ratio (HR) 1.20; 95% confidence interval (CI) 1.18-1.22; P < 0.001] and death from any cause by 10% (HR 1.10; 95% CI 1.09-1.12; P < 0.001). For the 1346 patients who were still alive at last follow-up, the median (range) duration of follow-up was 6.9 (0.1-19.7) years. CONCLUSIONS: Tumour size is significantly associated with metastases in patients with renal masses. Patients with tumours <3 cm have a low risk of synchronous metastatic disease.

Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia.

Gain-of-function NOTCH1 mutations are found in 50%-70% of human T cell acute lymphoblastic leukemia/lymphoma (T-ALL) cases. Gain-of-function NOTCH1 alleles that initiate strong downstream signals induce leukemia in mice, but it is unknown whether the gain-of-function NOTCH1 mutations most commonly found in individuals with T-ALL generate downstream signals of sufficient strength to induce leukemia. We addressed this question by expressing human gain-of-function NOTCH1 alleles of varying strength in mouse hematopoietic precursors. Uncommon gain-of-function NOTCH1 alleles that initiated strong downstream signals drove ectopic T cell development and induced leukemia efficiently. In contrast, although gain-of-function alleles that initiated only weak downstream signals also induced ectopic T cell development, these more common alleles failed to efficiently initiate leukemia development. However, weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition. These data show that induction of leukemia requires doses of Notch1 greater than those needed for T cell development and that most NOTCH1 mutations found in T-ALL cells do not generate signals of sufficient strength to initiate leukemia development. Furthermore, low, nonleukemogenic levels of Notch1 can complement other leukemogenic events, such as activation of K-ras. Even when Notch1 participates secondarily, the resulting tumors show "addiction" to Notch, providing a further rationale for evaluating Notch signaling pathway inhibitors in leukemia.

Metachronous renal tumours after surgical management of oncocytoma.

OBJECTIVE: • To assess the risk of metachronous renal cell carcinoma (RCC) and benign renal tumours after surgical treatment of primary renal oncocytoma. PATIENTS AND METHODS: • Patients treated for primary renal oncocytoma between 1970 and 2007 were identified. Tumours were reviewed by a urological pathologist and patients were followed for subsequent renal tumours. RESULTS: • Of 424 patients with a median follow up of 7.1 year, 17 (4.0%) patients were diagnosed with a metachronous renal tumour at a median of 3.0 years (range 0.3-16 years). Of the 17 metachronous tumours, eight were oncocytoma, four were RCC and five were not resected or biopsied. • Eleven metachronous tumours occurred after solitary unilateral oncocytoma, five occurred after multifocal unilateral oncocytoma, and one occurred after multifocal bilateral oncocytoma. • Estimated 10-year tumour-free and RCC tumour-free survival was 94.8% and 98.7%, respectively. Patients with primary multifocal oncocytoma were at higher risk of metachronous tumour (hazard ratio 4.0; P = 0.007). Initial oncocytoma size (hazard ratio 1.1; P = 0.11) was not highly associated with risk of tumour recurrence. CONCLUSIONS: • To our knowledge, we report the largest cohort of oncocytoma after surgical management. Metachronous renal neoplasm in a patient with previous oncocytoma is more likely to be benign compared with patients who present with a renal tumour for the first time. Multifocal primary oncocytoma is associated with metachronous renal tumours. • Overall, the risk of metachronous RCC in a patient with an oncocytoma is similar to that of the general population, which does not support the use of routine cross-sectioning imaging surveillance.

Percutaneous nephrolithotomy for large or multiple upper tract calculi and autosomal dominant polycystic kidney disease.

PURPOSE: Percutaneous nephrolithotomy is standard therapy for upper tract calculi larger than 2 cm. However, the role of percutaneous nephrolithotomy in patients with autosomal dominant polycystic kidney disease has not been well evaluated. We report our experience with percutaneous nephrolithotomy in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients with autosomal dominant polycystic kidney disease and subsequent renal calculi managed by percutaneous nephrolithotomy from October 1981 to the present. RESULTS: We identified 9 patients. Percutaneous nephrolithotomy was performed in 11 kidneys. Flank pain was the presenting symptom in 6 patients. Average stone burden was 2.5 cm (range 1.6 to 3.6). Two access tracts were necessary in 5 kidneys. No intraoperative complications occurred. In 2 kidneys a second stage endoscopic procedure with ultrasonic lithotripsy was required to achieve stone-free status. Nephrostogram 24 hours after the final procedure showed no residual stone fragments in 9 of 11 kidneys (82%). The remaining 2 patients underwent percutaneous basket extraction to render them stone-free. There were no postoperative complications or recurrent stones. No patient required blood transfusion. Mean followup was 2.7 years (range 0.3 to 4). Mean calculated creatinine clearance was stable at 85.6 (range 45.9 to 126.6) and 89.5 mg/dl per minute (range 39.6 to 126.6) preoperatively and at last followup, respectively (p = 0.783). CONCLUSIONS: Autosomal dominant polycystic kidney disease increased operative complexity, the need for multiple percutaneous access tracts and the likelihood of repeat endoscopy. Despite the altered anatomy percutaneous nephrolithotomy was a safe, efficacious approach for autosomal dominant polycystic kidney disease. At last followup there was no stone recurrence and renal function was stable.

Early results of chemotherapy with retroperitoneal lymph node dissection for isolated retroperitoneal recurrence of upper urinary tract urothelial carcinoma after nephroureterectomy.

PURPOSE: Retroperitoneal lymph nodes are a recognized site of relapse in patients undergoing nephroureterectomy (NU) for high grade upper tract urothelial carcinoma (UC). Retrospective studies suggest that retroperitoneal lymph node dissection (RPLND) may be curative at the time of NU for high grade upper tract UC. We hypothesized that chemotherapy followed by RPLND may successfully salvage select patients with isolated retroperitoneal relapse of upper tract UC following prior NU. MATERIALS AND METHODS: We identified four patients with metastatic UC isolated to the subdiaphragmatic retroperitoneal lymph nodes after NU for upper tract UC. These patients had either a stable response or a complete response to chemotherapy and subsequently underwent a complete full bilateral template RPLND. Our primary study endpoints were disease-specific survival and recurrence-free survival. RESULTS: There was no perioperative mortality or long lasting surgery related sequelae in any patient. Two patients had no pathologic evidence of viable cancer at RPLND and are disease-free at 56 and 74 months from surgery. Two patients had evidence of active residual disease and subsequently developed distant disease at 2 months and 32 months after surgery. Both of these patients died of progressive disease at 3 months and 42 months following RPLND. The 5 year DSS and RFS rates were 50% and 50%. CONCLUSIONS: Chemotherapy followed by RPLND for isolated retroperitoneal recurrence after NU for upper tract UC urothelial carcinoma is a feasible and safe treatment that may be potentially therapeutic in select patients.

Ultrasound-guided thrombin injection for the treatment of postcatheterization pseudoaneurysms.

BACKGROUND: This prospective study was designed to assess the safety and efficacy of using bovine thrombin injection to treat pseudoaneurysms. METHODS AND RESULTS: From April 1998 through December 1999, 70 pseudoaneurysm were injected with bovine thrombin under the guidance of color duplex ultrasound. The most superficial pseudoaneurysm chamber was entered with a 1.5-inch, 19- to 22-gauge or spinal needle. Bovine thrombin, in a 1000 U/cc solution, was injected into the chamber. A total of 36 women and 34 men underwent ultrasound-guided thrombin injection (UGTI). Their mean age was 69.5 years. Most pseudoaneurysms were associated with diagnostic cardiac catheterization or percutaneous coronary intervention (80%). Two pseudoaneurysms arose from the brachial artery; the remainder were in the groin. Twenty-one patients were being treated with either heparin or warfarin, and the majority of the others were on antiplatelet therapy with aspirin or clopidogrel. UGTI was successful in 66 of the 70 patients (94%). The first patient in the series had 2 attempts at thrombin injection and refused further attempts. Two patients had undergone stent graft placement and had short, wide tracts. Both of these patients required surgical repair of their pseudoaneurysms. The fourth patient had a nearly complete pseudoaneurysm thrombosis and was lost to follow-up on discharge. No arterial thrombotic events occurred. One patient had a soleal vein thrombosis in the ipsilateral leg. CONCLUSIONS: UGTI was safe and effective in 94% of patients with postcatheterization pseudoaneurysms. Anticoagulant use did not hinder successful thrombosis. UGTI should be the initial treatment of choice for patients with postcatheterization pseudoaneurysms.

Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation in type II diabetes.

We studied the effect of omega-3 fatty acids (omega 3FA) on glucose homeostasis and lipoprotein levels in eight type II (non-insulin-dependent)-diabetic subjects ingesting 8 g/day omega 3FA for 8 wk as marine-lipid concentrate capsules. After omega 3FA supplementation, fasting plasma glucose levels increased 22% (P = .005) and meal-stimulated glucose increased 35% (P = .036). The percentage of glucose elevation correlated with percentage ideal body weight (r = .73, P = .04). No significant changes were seen in fasting or meal-stimulated plasma insulin, glucose disposal, or insulin-to-glucagon ratios. Very-low-density lipoprotein cholesterol and triglyceride (TG) levels showed consistent reductions of 56% (P less than .001) and 42% (P less than .001), respectively, after omega 3FA supplementation. Total cholesterol levels decreased 7% (P less than .05) without alteration in low- or high-density lipoprotein cholesterol. Thus, omega 3FA supplementation at a dose of 8 g/day significantly improves plasma TG levels but increases fasting and meal-stimulated glucose concentrations in the type II diabetic patient not treated with insulin or sulfonylurea agents. Marine-lipid concentrate capsules supplying large amounts of omega 3FAs should be used cautiously in the type II diabetic patient.

Functional status of persons with diabetes-related lower-extremity amputations.

OBJECTIVE: It is reasonable to predict that diabetes-related lower-extremity amputations have a detrimental impact on quality of life. However, we are unaware of any study in the medical literature describing the functional level of diabetic patients with amputations. The objective of this study was to evaluate amputations among diabetic patients and to determine the functional level of these patients with the Sickness Impact Profile (SIP). RESEARCH DESIGN AND METHODS: We enrolled 124 patients with diabetes. Case subjects (n = 35) were defined as patients who had undergone amputation of the lower-extremity, and control subjects (n = 89) were defined as patients who had not undergone amputation. Study participants received a standard history and physical examination. RESULTS: Both the physical dimension scores (33.5 +/- 14.9 vs. 22.3 +/- 14.7, P < 0.001) and the total SIP scores (27.6 +/- 9.9 vs. 22.5 +/- 10.3, P = 0.013) were significantly higher for amputees. However, the psychosocial dimension scores were not significantly different between case and control subjects (14.9 +/- 8.9 vs. 15.2 +/- 10.0, P > 0.05). Post hoc analysis showed that the group of patients who had undergone transtibial amputation had a significantly higher total impairment score than patients who had not undergone amputation (P = 0.039). This is in contrast to patients with toe or midfoot amputations, for whom total impairment scores were not significantly higher than those for the control subjects. Interestingly, bilateral amputees did not have significantly higher scores on either SIP dimension compared with unilateral amputees. CONCLUSIONS: These findings exemplify the detrimental physical and psychosocial health status of patients with diabetes-related lower-extremity amputation.

Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid.

To determine if the ratio of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in fish oil had an effect on plasma lipid responses, we randomly fed eight normolipidemic men three 36%-fat diets containing primarily butter, EPA-rich pollock oil, or DHA-rich tuna or salmon-blend oils. Plasma EPA and DHA reflected the amounts in the diets. Compared with values for the butter diet, very-low-density lipoprotein (VLDL) triglycerides decreased equally (71-78%) with all diets; low-density lipoprotein (LDL) cholesterol (LDL-C) and apolipoprotein B decreased 26% and 13%, respectively, on the tuna and salmon-blend oil but did not change (-1%) and increased 19% with the pollock diet; high-density lipoprotein cholesterol (HDL-C) and lipoproteins A-I and A-II decreased with all diets but more with the pollock diet than with the tuna and salmon diets. The 23-31% decrease in total cholesterol on the tuna and salmon diets resulted mostly from decreased LDL-C whereas the 16% decrease on pollock oil resulted mostly from a decrease in HDL-C.

Effects of shellfish consumption on lipoproteins in normolipidemic men.

Eighteen normolipidemic males were fed six different species of shellfish; each shellfish was fed so that protein in shellfish equalled that in animal foods in the normal diet, with less than one-half of the amount of fat in animal foods allowed for preparation of the shellfish. Oyster, clam, crab, and mussel diets, low in cholesterol and high in n-3 fatty acids, lowered VLDL triglycerides and cholesterol and, except for the mussel diet, LDL and total cholesterol. Squid and shrimp diets, higher in cholesterol and lower in n-3 fatty acids, did not change the blood lipids. The ratio of LDL to HDL cholesterol was decreased on the oyster and mussel diets. Oyster, mussel, and squid diets increased HDL2 cholesterol. Cholesterol absorption was decreased on the oyster, clam, and mussel diets. When consumed with moderate dietary fat restriction, oysters, clams, mussels, and crab appear to be useful in hypolipidemic diets for normolipidemic men.

Effect of glyburide and omega 3 fatty acid dietary supplements on glucose and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.

Using a random crossover design, we examined the effects of glyburide for 4 wk on glucose, insulin, lipid, and lipoprotein metabolism in 10 men with non-insulin-dependent diabetes (NIDDM) receiving dietary fish-oil concentrates containing omega 3 (n-3) fatty acids (8 g/d). Compared with glyburide alone, fasting plasma glucose concentrations increased with fish oil. Although glyburide with fish oil decreased fasting glucose concentrations, they did not return to baseline. Basal insulin concentrations were unaltered by fish oil without or with glyburide; however, postprandial insulin concentrations were decreased by fish oil. Although total cholesterol and triglyceride concentrations were unchanged, very-low-density-lipoprotein cholesterol concentrations decreased and low-density-lipoprotein cholesterol rose and apolipoprotein B concentrations trended higher. Thus, glyburide only partially rectified the impaired fuel homeostasis associated with fish-oil supplements in patients with NIDDM. Therefore, we do not recommend intake of fish oil concentrates containing n-3 fatty acids in patients with NIDDM.

Effect of consumption of whole milk and skim milk on blood lipid profiles in healthy men.

A controlled crossover feeding study was conducted in eight males aged 20-36 y to compare the effects of skim milk and whole milk on blood lipids. For 6-wk diet periods, 236 mL/4191 kJ of skim or whole milk was consumed with a background diet designed according to the American Heart Association recommendations. Plasma lipids were analyzed at baseline and at 3 and 6 wk. After 6 wk, the mean total cholesterol concentration was 4.47 mmol/L with skim milk and 4.80 mmol/L with whole milk (P < or = 0.001); mean low-density-lipoprotein-cholesterol concentrations were 2.64 and 2.96 mmol/L, respectively (P < or = 0.001). Mean apolipoprotein B decreased with skim milk and increased with whole milk (P < or = 0.05). No statistically significant differences were observed for plasma high-density lipoprotein-cholesterol, triglyceride, apolipoprotein A-I, or fatty acids. Substitution of skim milk for whole milk may decrease the risk of coronary heart disease.

Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2.

SIOPEL 2 was a pilot study designed to test the efficacy and toxicity of two chemotherapy (CT) regimens, one for patients with hepatoblastoma (HB) confined to the liver and involving no more than three hepatic sectors ('standard-risk (SR) HB'), and one for those with HB extending into all four sectors and/or with lung metastases or intra-abdominal extra hepatic spread 'high-risk (HR) HB'. SR-HB patients were treated with four courses of cisplatin (CDDP), at a dose of 80 mg/m(2) every 14 days, delayed surgery, and then two more similar CDDP courses. HR-HB patients were given CDDP alternating every 14 days with carboplatin (CARBO), 500 mg/m(2), and doxorubicin (DOXO), 60 mg/m(2). Two courses of CARBO/DOXO and one of CDDP were given postoperatively. Between October 1995 and May 1998, 77 SR-HB (10 of whom were actually treated with the HR protocol) and 58 HR-HB patients were registered and all 135 could be evaluated. Response rates for the entire SR-HB and HR-HB groups were 90% (95% CI 80-96%) and 78% (95% CI 65-87%), and resection rates were 97% (95% CI 87-99%) and 67% (95% CI 54-79%) including several children undergoing liver transplantation. For SR-HB patients, 3-year overall and progression-free survivals were 91% (+/-7%) and 89% (+/-7%) and for the HR-HB group 53% (+/-13%) and 48% (+/-13%), respectively. The short-term toxicity of these regimens was acceptable, with no toxic deaths. A treatment strategy based on CDDP monotherapy and surgery thus appears effective in SR-HB but, despite CT intensification, only half of the HR-HB patients are long-term survivors. For SR-HB patients, the efficacy of CDDP monotherapy and the CDDP/DOXO ('PLADO') combination are now being compared in a prospective randomised trial (SIOPEL 3).

The effects of omega 3 and omega 6 fatty acid-enriched diets on plasma lipoproteins and apoproteins in familial combined hyperlipidemia.

There is abundant evidence that dietary omega 3 fatty acids effect a favorable change in lipoprotein profiles of normolipidemic individuals. However, there is relatively little information available on the lipoprotein responses of hyperlipidemic individuals at risk for premature coronary artery disease. We studied a group of subjects with familial combined hyperlipidemia (FCHL), as well as a group of normal controls, on three rigidly controlled diets differing primarily in their fatty acid composition. The normal subjects demonstrated significant reductions in total cholesterol, low density lipoprotein (LDL) cholesterol, and total apolipoprotein B (apo B) levels on both an omega 3 (salmon) and omega 6 (safflower) fatty acid-enriched diet when these were compared with a basal diet high in saturated fat. The primary difference in response to the polyunsaturated diets was the potent triglyceride-lowering effect of the salmon diet. The FCHL subjects demonstrated a response to the safflower diet similar to that observed in normals and also manifested a marked triglyceride lowering with the salmon diet. However, total cholesterol and total apo B levels were not lowered by the salmon diet, and LDL cholesterol and apo B levels exhibited an upward trend. Thus, individuals with FCHL, a common disorder associated with premature coronary artery disease, do not appear to have a favorable lipoprotein response to diets enriched in omega 3 fatty acids.

Lipid metabolism in pregnancy. VIII. Effects of dietary fat versus carbohydrate on lipoprotein and hepatic lipids and tissue triglyceride lipases.

UNLABELLED: We have asked, is hypertriglyceridemia in the fed state in pregnancy due to intolerance to exogenous fat, accumulation of endogenous triglycerides, or accumulation of remnants of d < 1.006 lipoprotein metabolism? To answer these questions, we fed fat-free diets high in starch or sucrose, or diets containing fat or fat plus cholesterol to pregnant and nonpregnant rats for 12 days until gestational day 21 (term = 22 days). Blood was obtained 0, 4, or 8 hr after removal of food from the cages. Lipid concentrations were determined in chylomicrons and very low, low, and high density lipoproteins. Hypertriglyceridemia in pregnancy exists on both starch and sucrose containing fat-free diets and is exaggerated 4 and 8 hr after food is removed from the cage. The triglyceride rise occurs in d < 1.006 lipoproteins. With fat feeding, chylomicron triglyceride concentrations are not significantly elevated in pregnant rats, 0 or 8 hr postabsorptively despite greater food intake in pregnancy. In contrast, very low density lipoprotein (VLDL) triglyceride concentrations are elevated at all times following fat feeding in pregnant compared to nonpregnant animals. A significant contribution of lipoprotein remnants to the triglyceride rise in d < 1.006 lipoproteins seems unlikely since an isolated increase in VLDL cholesterol is not observed. No statistically significant accumulation of hepatic triglycerides occurs on any diet in pregnancy. Diet induced shifts in adipose tissue and muscle lipoprotein lipase activity are exaggerated in pregnancy while hepatic lipase is unaffected. Fetal weight is similar on all diets except sucrose where weight is reduced. CONCLUSIONS: Hypertriglyceridemia in fed pregnant rats is due to an increase in endogenous triglycerides. Remnant lipid accumulation does not appear to contribute to the endogenous hypertriglyceridemia. There is no intolerance to exogenous (dietary) fat. The results are compatible with an unimpaired delivery of exogenous fat to fat oxidizing tissues thereby maximizing glucose availability for fetal growth.

Effect of shellfish consumption on cholesterol absorption in normolipidemic men.

Noncholesterol marine sterols, abundant in molluscan shellfish, could inhibit cholesterol absorption. Eight normolipidemic males were fed for 3 weeks each three natural food diets in which a mixture of oysters and clams, crab, or chicken was served as the primary source of animal protein. The diets were equalized for caloric distribution, cholesterol, and n-3 fatty acids, leaving the noncholesterol marine sterols in the oyster/clam diet (444 mg/2,000 kcal) as the potential lipid-modifying variable. Cholesterol absorption was measured by plasma isotope ratio after doses of oral 14C- and intravenously infused 3H-labeled cholesterol. Cholesterol absorption was lower (42 +/- 4%) during the oyster/clam diet than during the chicken (54 +/- 3%, P less than 0.01) or crab (55 +/- 3%, P less than 0.01) diet periods. There was no difference between the chicken and crab diet periods. Total plasma cholesterol and triglycerides, very low density lipoprotein cholesterol and triglycerides, and low density and high density lipoprotein (HDL) cholesterol were not significantly different between any of the diets. The ratio of the HDL2-/HDL3-cholesterol was higher following the oyster/clam diet (0.46 +/- 0.09) than the chicken diet (0.32 +/- 0.06, P less than 0.05). Plasma and red cell membrane n-3 fatty acids were not significantly different among the three diets, but red cell membrane n-3 fatty acids increased as a function of time regardless of dietary sequence.

The effect of training and diet on lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats.

Treadmill training for 1 hr/day for 10 wk did not significantly affect chylomicron, very low density, low density, or high density lipoprotein cholesterol in rats fed either a high carbohydrate (glucose) or high fat (coconut oil) diet. Lipoprotein lipase activity of heart, adipose tissue, and skeletal muscle fibers was also unaffected by training. Carbohydrate feeding, however, when compared to fat feeding significantly lowered all lipoprotein cholesterol values as well as heart and fast-oxidative-glycolytic muscle fiber lipase activity and, conversely, significantly elevated hepatic triglyceride lipase activity. Thus, in the rat, an alteration in the serum lipid profile did not occur as a result of training, but dietary differences did independently influence serum lipid levels and tissue enzyme activity. It is suggested that human studies need to control for the possible independent influence of dietary differences when investigating the effects of training on lipoprotein metabolism.

Effects of dihydropyridine drugs on reversal by imipramine of helpless behavior in rats.

The present study was undertaken in order to determine the effects of the dihydropyridine calcium channel blocker, nimodipine and the dihydropyridine calcium channel activator BAY k 8644, in the learned helplessness test in the rat. Nimodipine dose dependently (0.5-2 mg/kg per day) reversed the behavioral deficit induced by inescapable shocks. The reversal of helpless behavior by imipramine (32 mg/kg per day) was antagonized by BAY k 8644 (0.5 and 1 mg/kg per day), and the effects of imipramine 8 and 16 mg/kg per day) were potentiated by a subeffective dose (0.5 mg/kg per day) of nimodipine. These results suggest that central dihydropyridine binding sites may be specifically involved in the modulation of the imipramine reversal of helpless behavior and favor a physiological role for dihydropyridine binding sites in the brain.