Biomedical subjects

J Blumberg

Publications and source records attributed to J Blumberg.

At least 19 recordsLinked to original sources

PubMed2006

Plasma antioxidants in subjects before hematopoietic stem cell transplantation.

UNLABELLED: Chemo-irradiation induced oxidative damage to vascular endothelium may contribute to pulmonary complications of hematopoietic stem cell transplantation (HSCT). We measured antioxidants, markers of oxidative stress and plasma antioxidant capacity in plasma or serum from 24 subjects at day 7 before HSCT and 20 control subjects. The plasma concentration of extracellular glutathione peroxidase (GPX-3) was significantly reduced in the HSCT subjects compared with controls (HSCT: 98+/-42 microg/ml, control: 169+/-56 microg/ml, P<0.0001). The concentration of gamma-tocopherol was significantly higher in the HSCT subjects compared with controls (HSCT: 207+/-103 microg/dl; CONTROL: 98+/-52 microg/dl; P=0.0002). The plasma concentrations of protein carbonyl, nitrotyrosine, malondialdehyde, alpha-tocopherol, vitamin A, homocysteine, cysteine and cysteinylglycine did not differ between HSCT and control subjects. Plasma from HSCT subjects was as effective as control plasma in quenching menadione-induced intracellular reactive oxygen species production in human microvascular endothelial cells. In summary, subjects before HSCT have significantly reduced plasma concentrations of GPX-3, elevated plasma gamma-tocopherol yet retains the ability to quench an acute oxidative stress. These changes may play a role in chronic oxidative stress in the HSCT population.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Mechanical stimulation promotes osteogenic differentiation of human bone marrow stromal cells on 3-D partially demineralized bone scaffolds in vitro.

Bone is a dynamic tissue that is able to sense and adapt to mechanical stimuli by modulating its mass, geometry, and structure. Bone marrow stromal cells (BMSCs) are known to play an integral part in bone formation by providing an osteoprogenitor cell source capable of differentiating into mature osteoblasts in response to mechanical stresses. Characteristics of the in vivo bone environment including the three dimensional (3-D) lacunocanalicular structure and extracellular matrix composition have previously been shown to play major roles in influencing mechanotransduction processes within bone cells. To more accurately model this phenomenon in vitro, we cultured human BMSCs on 3-D, partially demineralized bone scaffolds in the presence of four-point bending loads within a novel bioreactor. The effect of mechanical loading and dexamethasone concentration on BMSC osteogenic differentiation and mineralized matrix production was studied for 8 and 16 days of culture. Mechanical stimulation after 16 days with 10 nM dexamethasone promoted osteogenic differentiation of BMSCs by significantly elevating alkaline phosphatase activity as well as alkaline phosphatase and osteopontin transcript levels over static controls. Mineralized matrix production also increased under these culture conditions. Dexamethasone concentration had a dramatic effect on the ability of mechanical stimulation to modulate these phenotypic and genotypic responses. These results provide increased insight into the role of mechanical stimulation on osteogenic differentiation of human BMSCs in vitro and may lead to improved strategies in bone tissue engineering.

Adult↗

PubMed2001

Dynamic stabilization in 1sigma(u)-->1pi(g) excited nitrogen clusters.

High-resolution 1s near-edge spectra of molecular nitrogen and variable size nitrogen clusters obtained using monochromatic synchrotron radiation from the high brilliance BESSY-II storage ring facility are reported. The vibrationally resolved 1sigma(u)-->1pi(g) core-to-valence excitation band of clusters shows a distinct redshift of 6+/-1 meV relative to the isolated molecule, but the vibrational structure and linewidths are essentially unchanged. This shift is assigned to dynamic stabilization of 1sigma(u)-->1pi(g) excited molecules in clusters, arising from the dynamic dipole moment generated by core-hole localization in the low-symmetry cluster field. This leads to changes in intermolecular interactions compared to the ground-state cluster. Such spectral shifts are expected to occur generally in molecular clusters and in the corresponding condensed phase.

Journal Article↗

PubMed2000

Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance.

BACKGROUND: The somatostatin analogues lanreotide and octreotide have previously been shown to be effective in controlling flushing and diarrhea in patients with carcinoid syndrome. As lanreotide requires injection only every 10 days, compared with twice-daily injections of octreotide, a direct comparison between these two treatments in terms of patient acceptability, patient preference, and efficacy in controlling symptoms was performed in patients with carcinoid syndrome. METHODS: Thirty-three patients with carcinoid syndrome were included in an open, multicenter, crossover study. Half of the patients received octreotide 200 microg subcutaneously twice or thrice daily for 1 month followed by lanreotide 30 mg intramuscularly every 10 days for 1 month, while the other half commenced with lanreotide followed by octreotide in a similar fashion. Quality-of-life assessments were performed at each visit and patient preference for one of the two treatments evaluated. The number and intensity of flushing episodes and bowel movements, urinary 5-hydroxyindoleacetic acid (5HIAA) levels, and plasma serotonin levels were recorded. RESULTS: No significant differences were found between lanreotide and octreotide in terms of quality of life. The majority of patients (68%) preferred lanreotide (P = 0.03), largely due to its simplified mode of administration. Disappearance or improvement in flushes occurred in 53.8% of patients (14 of 26) while on lanreotide and in 68% (17 of 25) on octreotide. A disappearance or improvement of diarrhea in 45.4% (10 of 22) on lanreotide, compared with 50% (11 of 22) on octreotide, was also observed. Lanreotide and octreotide were equally effective in reducing urinary 5HIAA levels and plasma serotonin levels. Both treatments were well tolerated, with mild symptoms of abdominal pain and nausea observed in 29% and 14% receiving octreotide and lanreotide, respectively. CONCLUSIONS: Lanreotide and octreotide are equally efficacious in terms of symptom control and reduction in tumor cell markers for patients with carcinoid syndrome. Due to its simplified mode of administration, most patients prefer treatment with lanreotide.

Antineoplastic Agents↗

PubMed2000

Efficacy and tolerability of the long-acting somatostatin analog lanreotide in acromegaly. A 12-month multicenter study of 58 acromegalic patients. French Multicenter Study Group on Lanreotide in Acromegaly.

OBJECTIVE: To determine the effects of the new somatostatin analogue, lanreotide, in its prolonged released form (PR), in patients with acromegaly. DESIGN: Prospective open multicenter non comparative study. SETTING: Thirty-three university-affiliated medical centers. PATIENTS: One hundred sixteen acromegalic patients with active disease, of whom 58 patients complied with the protocol and completed the 12-month period treatment. INTERVENTION: Lanreotide PR treatment was started at a dose of 30 mg intramuscularly every 14 days. If integrated mean plasma GH levels were not below 5 micrograms/L and/or IGF-I levels were not normalized after one month of treatment, injections were given every 10 days. The duration of the study was 12 months. RESULTS: After one month of treatment mean plasma GH and IGF-I levels had fallen from 10.7 +/- 11.1 micrograms/L (mean +/- SD; range, 2.6-74.8 micrograms/L; median, 7 micrograms/L) and 718 +/- 270 micrograms/L (range 338-1440 micrograms/L; median, 645 micrograms/L), respectively, to 7.8 +/- 10.1 micrograms/L and 575 +/- 252 micrograms/L, respectively. Thirty patients (22%) had plasma GH levels below 2.5 micrograms/L, and 8 patients (16%) had age-adjusted normal plasma IGF-I levels. At the sixth month of treatment mean plasma GH levels of 2.5 micrograms/L or less, and normal plasma IGF-I levels were observed in 33%, and 33% of patients, respectively. At the twelvth month of treatment, these percentages were 41%, and 41%, respectively. The interval between two injections was shortened (one injection every 10 days) in 8 of the 58 patients (13%) at the second month of treatment, and at the end of the study, 70% of patients required 3 injections per month. The most frequent adverse event elicited by enquiry was transient diarrhea (76% of patients), followed by abdominal pain (62%) and pain at the injection site (59%). Based on the analysis of a subgroup of 46 patients who had at least a measurement of fecal fat content after day 0 of the study, a non significant increase (from 4.2 +/- 3.4 to 5.1 +/- 4.3 g/24 h, p = 0.3) in mean steatorrhea was observed during treatment. Before treatment, steatorrhea was present in 9 (19%) patients. During the study, 15 additional patients (32%) developed persistent steatorrhea, and there was a transient increase in fecal fat content above 6 g/24 h in another 11 patients. After exclusion of the 7 patients (12%) with gallstones at enrollment, new gall-stones were diagnosed in 6 out of 50 patients (12%) during the study. CONCLUSION: Two or three monthly injections of lanreotide PR decreased GH concentration to less than 2.5 micrograms/L and normalized IGF-I levels in 41% of patients treated during 12 months. The good tolerability of this treatment, and the reduction in the frequency of injections, plus the sustained drug serum concentrations, confirm the usefulness of this new somatostatin analog formulation.

Academic Medical Centers↗

PubMed2000

The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors.

OBJECTIVE: Somatostatin analogs are the first-line drugs for controlling hormone-mediated symptoms of carcinoid tumors. Prospective and retrospective studies have suggested that somatostatin analogs also have antiproliferative activity. The octapeptide lanreotide is available in sustained-release form, obviating the need for daily injections. METHODS: A total of 46 patients were enrolled in this open, prospective, phase II trial. They received lanreotide 30 mg i.m. every 14 days for 6 months when they had symptomatic carcinoid tumors, and lanreotide 30 mg i.m. every 10 days if they had nonsymptomatic tumors. Nonsymptomatic tumors were progressive before the start of the study. Tumor size was assessed every 3 months by means of computed tomography. The assessment was centralized and was made by an external panel. RESULTS: In all, 30 patients had symptomatic neuroendocrine tumors and 16 had asymptomatic neuroendocrine tumors. Five patients in the group with symptomatic tumors and two in the group with nonsymptomatic tumors were considered not to be evaluable. The mean duration of treatment was 12 months in the group with symptomatic tumors and 13 months in the other group. Among the 39 evaluable patients, two objective responses were obtained, giving an objective response rate of 5% (one in the group with symptomatic tumors and one in the other group). Nineteen patients had no significant increase in their tumor size for a mean of 9.5 months. CONCLUSIONS: Lanreotide is safe and well tolerated in patients with carcinoid tumors. It seems to have both symptomatic and antitumoral effects in this setting.

Antineoplastic Agents↗

PubMed2000

Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide.

Somatostatin analogs have been shown to be effective for the treatment of TSH-secreting pituitary adenomas. However, their use in this indication is limited by the fact that available analogs require several daily sc injections. The present study was performed to evaluate the effects of a slow release formulation of the somatostatin analog lanreotide (SR-L) on both hormone secretion and tumor size and to assess the tolerance in a series of thyrotropinomas treated for 6 months. Eighteen patients with hyperthyroidism related to a TSH-secreting pituitary adenoma, evidenced by pituitary magnetic resonance imaging, were studied. After a basal assessment, each patient received 30 mg SR-L, im, every 14 days for 1 month. Then, according to the free T3 (fT3) plasma level measured, 9 of 18 patients were injected twice monthly, and 7 of 18 patients received SR-L every 10 days for 5 additional months. One patient was dismissed from the study in month 1 of the study for side-effects and another in month 3 for noncompliance to the protocol. Clinical and biological evaluations (plasma TSH, free alpha-subunit, fT4, fT3, and lanreotide levels) were performed before and in months 1, 3, and 6 of treatment. Pituitary magnetic resonance imaging and gallbladder ultrasonography were performed both at entry and at the end of the study. Clinical signs of hyperthyroidism improved within 1 month in all 16 evaluable patients. Mean (+/- SEM) plasma lanreotide levels reached 1.11 +/- 0.43 and 1.69 +/- 0.65 ng/mL in month 3 using 2 and 3 injections/month, respectively, then remained stable until the end of the study. During therapy, the plasma TSH level decreased from 2.72 +/- 0.32 to 1.89 +/-0.27 mU/L (P < 0.01), with parallel significant changes in free alpha-subunit. During the same period, plasma fT4 and fT3 levels decreased from 37.9 +/- 2.9 to 19.7 +/- 2.3 pmol/L (P < 0.01) and from 14.6 +/- 1.1 to 8.3 +/- 0.8 pmol/L (P < 0.01), respectively. No statistically significant change in mean adenoma size was observed after 6 months of treatment. Side-effects, including pain at the injection point, abdominal cramps, and diarrhea, were mild and transient and did not lead to interruption of the treatment. No gallstones occurred during the study. SR-L appears to be able to suppress clinical signs of hyperthyroidism in our series of patients with TSH-secreting pituitary adenomas. The analog also reduces plasma TSH and thyroid hormone levels, which were normalized in 13 of 16 cases. The effect was maintained throughout the treatment using 2 or 3 SR-L injections monthly without any problem of tolerance. We conclude that SR-L is a safe and effective treatment of thyrotropinomas and avoids the drawbacks of the modes of administration of other somatostatin analogs, given three times daily.

Adenoma↗

PubMed1999

A multicenter phase II study with triptorelin (sustained-release LHRH agonist) in advanced or recurrent endometrial carcinoma: a French anticancer federation study.

The objective of this phase II multicenter study was to assess the efficacy and tolerance of triptorelin (a sustained-release LHRH agonist) in advanced or recurrent endometrial cancer. A total of 101 monthly intramuscular injections were administered to 24 eligible patients (median number/patient = 3; range 1-12). Mainly due to progression, only 16 patients received 3 or more injections. Among the 23 evaluable patients, 1 complete and 1 partial response (response rate of 8.7%) and 5 disease stabilizations were observed, often of long duration, but never in an irradiated area or after progestogens treatment failure. Median survival for eligible patients was 7.2 months (range: 1-36 months). Only grade 1 toxicities possibly related to the treatment were observed in 4 patients. In conclusion, triptorelin was safe, well tolerated, and easily manageable, and the very low toxicity did not impair the quality of life in these patients with a very poor prognosis. Although the response rate was disappointing, several patients showed early evidence of efficacy which may be of long duration. Response rates range between 0 and 45% in different published studies. Additional studies with stricter inclusion criteria and a larger sample size are necessary to better evaluate the role of LHRH agonists in endometrial adenocarcinomas.

Adult↗

PubMed1999

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Animals↗

PubMed1999

Industrial hygiene recommendations as interventions: a collaborative model within occupational medicine.

The authors conducted a cross-sectional telephone survey of patients and employers to evaluate the effectiveness of conducting industrial hygiene work site visits as part of the medical management of clinic patients with suspected occupational disease. Industrial hygiene interventions were intended to keep the index patient from ongoing exposure while simultaneously protecting co-workers from future disease. The demographics of the 76 work sites and patients are summarized. According to the employers, 78 percent had implemented at least one recommended intervention, and 52 percent of the employers had implemented the priority intervention. The factors associated with the employers' implementation of the recommended industrial hygiene controls are presented. Employers were 3.7 times more likely to implement the priority intervention (p = .04) if they believed a worker's illness was work-related. Employers with joint labor-management health and safety committees were 3.8 times as likely to implement the priority intervention (p = 0.04). The factors associated with changes in the patients' self-reported disease status are explored and the social and economic implications of this model, are discussed. Patients who reported an improvement in disease status were 5.5 times more likely to have maintained or increased their salary (p = 0.03). Patients were 10.4 times more likely to be working if the employer had implemented any intervention (p = 0.02) and 13.3 times more likely if the priority intervention (p = 0.01) had been adopted. Those patients who left their original employer suffered a median decrease in salary of 35 percent if they found work with a different employer and a 90 percent decrease when they failed to find a new job.

Connecticut↗

PubMed1999

Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty.

The impact of treatment of central precocious puberty (CPP) with GnRH agonists on final statural height (FH) remains controversial, and guidelines on the optimal time point for interruption of these treatments have not been established. We analyzed the long term results of 58 girls and 8 boys uniformly treated with triptorelin slow release formulation (Decapeptyl, triptorelin-SR) for CPP and compared their FH with predicted height before treatment and with the FH of a historical group of patients not treated with GnRH agonist. The FH SD score was close to 0 and was not different from the genetic target height. In girls, FH was improved by 4.8 +/- 5.8 cm compared with predicted height before treatment and by 8.3 cm by comparison with a historical group. In boys, comparison with a historical group revealed a 13.7-cm improvement, whereas predicted height before treatment was similar to FH. Three variables were independently associated with FH in girls: the bone age/statural age ratio at the onset of treatment (negatively), the height SD score at the end of treatment, and the posttreatment growth spurt (delta FH - height at the end of treatment). The influence of the posttreatment growth spurt, itself dependent on age and bone age at the interruption of treatment, suggests that continuing treatment beyond the age of 11 yr in girls does not improve and could actually decrease FH. This point should be evaluated in a formal controlled trial.

Age of Onset↗

PubMed1998

Redox regulation of ubiquitin-conjugating enzymes: mechanistic insights using the thiol-specific oxidant diamide.

The ubiquitin-proteasome pathway (UPP) regulates critical cell processes, including the cell cycle, cytokine-induced gene expression, differentiation, and cell death. Recently we demonstrated that this pathway responds to oxidative stress in mammalian cells and proposed that activities of ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s) are regulated by cellular redox status (i.e., GSSG:GSH ratio). To test this hypothesis, we altered the GSSG:GSH ratio in retinal pigment epithelial cells with the thiol-specific oxidant, diamide, and assessed activities of the UPP. Treatment of cells with diamide resulted in a dose-dependent increase in the GSSG:GSH ratio resulting from loss of GSH and a coincident increase in GSSG. Increases in the GSSG:GSH ratio from 0.02 in untreated cells to > or = 0.5 in diamide-treated cells were accompanied by dose-dependent reductions in the levels of endogenous Ub-protein conjugates, endogenous E1-ubiquitin thiol esters, and de novo ubiquitin-conjugating activity. As determined by the ability to form E1-ubiquitin and E2s-ubiquitin thiol esters, E1 and E2s were both inhibited by elevated GSSG:GSH ratios. Inhibition of E1 was associated with the formation of E1-protein mixed disulfides. Activities of E1 and E2s gradually recovered to preoxidation levels, coincident with gradual recovery of the GSSG:GSH ratio. These data support S-thiolation/dethiolation as a mechanism regulating E1 and E2 activities in response to oxidant insult. Ubiquitin-dependent proteolytic capacity was regulated by the GSSG:GSH ratio in a manner consistent with altered ubiquitin-conjugating activity. However, ubiquitin-independent proteolysis was unaffected by changes in the GSSG:GSH ratio. Potential adaptive and pathological consequences of redox regulation of UPP activities are discussed.

Cell Line, Transformed↗

PubMed1998

Three-month sustained-release form of triptorelin in patients with advanced prostatic adenocarcinoma: results of an open pharmacodynamic and pharmacokinetic multicenter study.

The pharmacodynamics and the pharmacokinetic characteristics of a new longer-acting formulation containing 11.25 mg of triptorelin (Decapeptyl) to be administered every 3 months were evaluated in 14 patients with advanced prostate carcinoma. After one single injection, the mean time to reach the surgical castration testosterone range is 22 days, and this effective testosterone suppression is maintained for the 3-month therapy. After a first plasma surge (35.70 ng/ml) occurring 2.5 h after injection and a rise between day 17 and day 31 (maximum on day 24: 0.32 ng/ml), the mean triptorelin plasma level is stable (0.06 +/- 0.05 ng/ml) and maintained until day 91. This new formulation was well tolerated both locally and systemically.

Adenocarcinoma↗

PubMed1997

Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress.

Upon oxidative stress cells show an increase in the oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio with a concomitant decrease in activity of the ubiquitinylation pathway. Because most of the enzymes involved in the attachment of ubiquitin to substrate proteins contain active site sulfhydryls that might be covalently modified (thiolated) upon enhancement of GSSG levels (glutathiolation), it appeared plausible that glutathiolation might alter ubiquitinylation rates upon cellular oxidative stress. This hypothesis was explored using intact retina and retinal pigment epithelial (RPE) cell models. Exposure of intact bovine retina and RPE cells to H2O2 (0.1-1.7 micromol/mg) resulted in a dose-dependent increase in the GSSG:GSH ratio and coincident dose-dependent reductions in the levels of endogenous ubiquitin-activating enzyme (E1)-ubiquitin thiol esters and endogenous protein-ubiquitin conjugates and in the ability to form de novo retinal protein-125I-labeled ubiquitin conjugates. Oxidant-induced decrements in ubiquitin conjugates were associated with 60-80% reductions in E1 and ubiquitin-conjugating enzyme (E2) activities as measured by formation of ubiquitin thiol esters. When GSH levels in RPE cells recovered to preoxidation levels following H2O2 removal, endogenous E1 activity and protein-ubiquitin conjugates were restored. Evidence that S thiolation of E1 and E2 enzymes is the biochemical link between cellular redox state and E1/E2 activities includes: (i) 5-fold increases in levels of immunoprecipitable, dithiothreitol-labile 35S-E1 adducts in metabolically labeled, H2O2-treated, RPE cells; (ii) diminished formation of E1- and E2-125I-labeled ubiquitin thiol esters, oligomerization of E225K, and coincident reductions in protein-125I-labeled ubiquitin conjugates in supernatants from nonstressed retinas upon addition of levels of GSSG equivalent to levels measured in oxidatively stressed retinas; and (iii) partial restoration of E1 and E2 activities and levels of protein-125I-labeled ubiquitin conjugates in supernatants from H2O2-treated retinas when GSSG:GSH ratios were restored to preoxidation levels by the addition of physiological levels of GSH. These data suggest that the cellular redox status modulates protein ubiquitinylation via reversible S thiolation of E1 and E2 enzymes, presumably by glutathione.

Animals↗

PubMed1997

Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake.

PURPOSE: Given the recent correlation between nutrition and risk for eye disease, there is keen interest in a possible correlation between nutrient intake and eye-tissue nutrient levels. In this work, the objective was (1) to determine, for the first time, the relation between dietary intake of vitamin C and eye tissue levels of the vitamin in free-living humans, (2) to determine the relation between levels of the vitamin in plasma, lens and aqueous, and (3) to compare this information to data gathered for a carefully reared group of guinea pigs that were fed different levels of vitamin C. METHODS: Two hundred sixty-five cataract patients (mean age = 72 years) from a clinical practice were recruited for this study. One hundred thirty-two patients provided the dietary intake data via a food frequency questionnaire, which we used for this work. Plasma, aqueous humor, and lens samples were obtained at the time of lentectomy and preserved for vitamin C analysis. Comparable samples were obtained from male Hartley white guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear statistical models were also used to characterize the relation between vitamin C intake and human ocular tissue levels of the vitamin and to examine potential confounding and the effect of modification by age and sex. RESULTS: In humans, plasma and aqueous vitamin C concentrations were related to intake in a log-linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best fit of vitamin C levels in lens and diet predicts a linear relationship with a sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake, although a log-linear relation can also be modeled. In guinea pigs, diet was related to eye tissue and plasma levels of the vitamin by a log10 linear relationship in all cases. Vitamin C in human lens was linearly related to plasma and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma was related to aqueous and lens vitamin C by log10-linear relationships, whereas lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day. However, a saturating relationship between lens vitamin C and dietary intake in humans was not indicated in this study, although such a relationship is seen in guinea pigs. Intertissue relations between vitamin C levels in humans and guinea pigs are similar for some but not all relations.

Adult↗

PubMed1997

Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans.

AIMS: Lanreotide is a novel synthetic somatostatin analogue. A long-acting formulation of lanreotide has been shown to be effective for the treatment of gastroentero-pancreatic hormone-producing tumours but effects on postprandial digestive and absorptive functions remain obscure. The aim of the present study was to evaluate the effects of intravenous lanreotide on gastric and biliopancreatic secretions in man as well as the absorption of nutrients and the duodeno-caecal transit time after ingestion of an homogenized meal (500 kcal, 55% carbohydrates, 15% proteins, 30% lipids). METHODS: Eight healthy male volunteers were studied on two occasions within a 2 weeks interval, using a perfusion method. They received in single-blind and random order continuous i.v. infusion of either placebo or lanreotide (100 micrograms h-t after a bolus of 100 micrograms 15 min before the beginning of the study). RESULTS: Lanreotide significantly decreased gastric acid secretion (90%) for the initial 3 h period. Gastric emptying was not significantly modified by lanreotide infusion. Compared with placebo, lanreotide almost completely abolished both bile salts and lipase responses to the meal. It largely increased the duodeno-caecal transit time and decreased significantly the duodenal absorption of carbohydrates and triglycerides. CONCLUSIONS: Since lanreotide has powerful effects on gastrointestinal functions, it could be useful in the prevention or in the treatment of pancreatic and bowel fistulas as well as short bowel syndrome.

Adult↗

PubMed1997

A randomized comparison of the clinical and hormonal effects of two GnRH agonists in patients with prostate cancer.

OBJECTIVE: The aims of the study were (i) to compared the efficacy of the two long-acting GnRH agonists (GnRHa) triptorelin (Trp) and leuprolide (Leu) in men with prostate cancer and (ii) to assess the pattern of plasma testosterone levels following each injection of GnRHa. PATIENTS AND METHODS: 67 patients referred for prostate cancer not suitable for surgery were randomly allocated to two treatment regimens: 33 patients received 3.75 mg Trp i.m. at 4-week intervals for 3 months and 34 patients were treated with 3.75 mg Leu s.c. at the same rhythm of administration for 3 months. RESULTS: Clinical data at entry and assessed monthly during follow-up did not differ between the two groups. Plasma prostate-specific antigen (PSA) and testosterone were measured before, 24 and 72 h after each injection of GnRHa. During treatment, PSA dropped similarly in both groups. By month 2, testosterone was < 1.0 nmol/l in 77 and 48% of patients treated with Trp and Leu, respectively (p = 0.02). 24 and 72 h after GnRHa injection, 77 (Trp) and 56% (Leu) of patients had testosterone < 1.0 nmol/l (p < 0.05). CONCLUSIONS: The second and third injections of GnRHa were not followed by a significant increase in testosterone. Trp induced a higher decrease in testosterone than did Leu. The implications in terms of survival should, however, be studied in a larger and longer study.

Antineoplastic Agents, Hormonal↗

PubMed1997

Nutritional needs of seniors.

Aging is accompanied by a variety of economic, psychologic, and social changes that can compromise nutritional status. Aging also produces physiologic changes that affect the need for several essential nutrients. While nutritional status surveys of the elderly have shown a relatively low prevalence of frank nutrient deficiencies, there is a marked increase in risk of malnutrition and evidence of subclinical deficiencies with a direct impact on function. A critical risk factor of malnutrition among older adults is their declining need for energy due to a reduction in the amount of lean body mass and a more sedentary lifestyle. Decreasing energy intake with advancing age has important implications for the diet in terms of protein and micronutrients. Dietary quality is difficult to ensure when overall energy intake is low. The gap between actual nutrient consumption common among older adults and the recommended intakes from diets associated with health promotion and prevention of chronic diseases is large. The significance of sound nutrition education and the adverse impact of consumer misinformation about the benefits of these food choices becomes clear with the recognition that nutritional status influences the rate of physiologic and functional declines with age. New dietary guidelines for the elderly should emphasize the value of high quality, nutrient-dense foods. This approach will require new efforts in consumer education sensitive to the needs and beliefs of older people.

Aged↗