Biomedical subjects

S Jacobs

Publications and source records attributed to S Jacobs.

At least 37 records · Page 2Linked to original sources

PubMed1996

Hormone replacement therapy in the aged. A state of the art review.

The use of hormone replacement therapy (HRT) in the immediate postmenopause for the relief of menopausal symptoms and for the prevention of osteoporosis and cardiovascular disease is well established. The continuation of treatment beyond the age of 60 years is likely to maximise these long term benefits and there is now increasing evidence to suggest that commencing treatment de novo in women of this age is likely to be beneficial. Many women remain symptomatic well into their sixties and the introduction of HRT at this stage will not only relieve these symptoms but will also conserve bone density and reduce future osteoporotic fracture risk. Furthermore, HRT appears to reduce the risk of cardiovascular disease, even in those women with pre-existing heart disease. The possible association between HRT and breast cancer remains controversial. Overall, there seems to be a slight increase in risk with long term HRT usage (longer than 10 years) but certain subgroups of women may be more at risk. This review discusses the merits and potential problems of prescribing HRT to the elderly and gives some guidance on the type, dose and route of administration of estrogen and progestogen to be used. Poor compliance with HRT is a major problem and the more widespread use of pretreatment counselling together with a wider range of products should have a positive impact in this area. The final decision about whether to continue or commence HRT in the elderly should be an informed one made by the woman and her clinician together.

Administration, Oral↗

PubMed1996

Cerebral SPECT imaging: effect on clinical management.

This study, performed in 94 consecutive patients referred for evaluation, demonstrates the clinical utility of cerebral SPECT imaging. In a significant percentage of patients (47%), the additional information provided by SPECT resulted in an alteration in clinical management. Long-term follow-up will be necessary to determine the effect of these management decisions on patient outcome.

Brain↗

PubMed1995

Activity of melphalan in combination with the glutathione transferase inhibitor sulfasalazine.

Glutathione (GSH) transferases (GST), a family of detoxification enzyme proteins, are suggested to play an important role in tumor cell resistance to melphalan. The GST-activity inhibitor ethacrynic acid has been shown to increase the antitumor activity of melphalan in vitro as well as in vivo. In this study we determined the activity and toxicity of melphalan in combination with another GST-activity inhibitor, sulfasalazine, an agent used to treat ulcerative colitis. We entered 37 previously treated patients with advanced cancer of different histologies on sulfasalazine given at the individually calculated maximum tolerated dose (MTD) and melphalan given at doses beginning at 20 mg/m2. The main toxicity arising from this combination was nausea and vomiting, whereas increased myelosuppression was not observed. A partial response was seen in 2/4 of the ovarian cancer patients only. Plasma sulfasalazine levels varied between 2.5 and 47.1 micrograms/ml. Although reductions in GSH/GST levels were observed in peripheral mononuclear cells of certain patients following sulfasalazine treatment, there was no correlation between the extent of reduction and the plasma sulfasalazine level. A larger patient population must be studied to determine the usefulness of this combination.

Drug Administration Schedule↗

PubMed1995

The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients.

This study investigated the influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E2) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E2 was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3% +/- 9.5%, 70.0% +/- 5.1% and 57.3% +/- 5.3%, respectively (mean +/- SEM). Corresponding values for plasma E2 suppression were 30.7% +/- 6.5%, 43.4% +/- 4.5% and 42.9% +/- 6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E2 levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E2 suppression was observed. The suppression of E2 by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.

Administration, Oral↗

PubMed1995

A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls.

OBJECTIVES: Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder of unknown etiology. We tested the hypothesis that a microorganism would be found at higher prevalence in urine or bladder tissue from women with IC than from control women. METHODS: Urine and bladder tissue were obtained at cystoscopy from 11 IC patients and 7 control subjects. These specimens were cultured for a variety of fastidious and nonfastidious bacteria, mycobacteria, fungi, and viruses. In addition, special staining techniques were used to examine biopsy specimens and cytospun urine, and tissue sections and outgrowths of explanted bladder cells were examined by electron microscopy. RESULTS: Cultures of urine from 6 of 11 IC patients grew five different bacteria (Corynebacterium sp. Klebsiella pneumoniae, Lactobacillus sp, Streptococcus constellatus, and Streptococcus morbillorum), human cytomegalovirus, or Torulopsis glabrata; one of these organisms (Lactobacillus sp) was found in urine from 2 patients. Although contamination by urethral organisms is possible, the prevalence of microorganisms in urine of IC patients (6 of 11) was significantly greater than in urine of control subjects (0 of 7) (P < 0.05). Acridine orange staining revealed rods with appropriate morphology in urine from 4 of the 5 IC patients who had positive bacterial cultures and yeastlike organisms in urine and bladder tissue specimens that grew Torulopsis. Additionally, rodlike organisms were seen in urine from 2 IC patients with negative bacterial cultures and cocci were seen in the urine of 1 control patient. Biopsy specimens from 2 IC patients grew Torulopsis sp or Lactobacillus sp, in agreement with the results of acridine orange staining and culture of urine from these patients; in contrast, specimens from 3 control subjects grew small numbers of Pseudomonas sp or Staphylococcus epidermidis, but no organisms were cultured from urine or seen in acridine orange-stained tissue smears. All other cultures and stains were negative. CONCLUSIONS: These data do not provide evidence that IC is associated with infection or colonization by a single microorganism. However, they do generate the hypothesis that the prevalence of microorganisms, especially bacteria at low concentrations, is greater in the urine of IC patients than of control subjects. If these results are confirmed by other controlled studies, the question of whether the presence of these organisms is a cause or a result of IC should be addressed.

Biopsy↗

PubMed1995

Comparative clearance performance of two dialyser units used in the CVVHD mode.

Continuous renal replacement therapies are now commonly used modes of support in acute renal failure (ARF). This study compared the clearance performance and it's degradation over time of two dialysers, one of flat plate configuration, and one of hollow fibre configuration (Asahi PAN 06 hollow fibre dialyser, Domedica, Sydney, and Hospal AN69HF flat plate dialyser, Gambro, Sydney) used in the CVVHD mode. Data were obtained from seven patients. Urea clearance was determined at commencement of dialysis and then at 12 hour intervals up to 48 hours post commencement. At each study time, urea clearance was determined at dialysis fluid (DF) flows of 500, 1000, 1500 and 2000 ml/hr. The procedure was repeated for each patient using the alternate dialyser. Comparisons of the two dialyser's urea clearance did not demonstrate any significant difference at any of the time periods studied. Overall, clearance was dependent upon (DF) flow with the diffusive clearance initially equal to DF flow but falling to 0.7 and 0.85 times increase in DF flow at 48 hours.

Acute Kidney Injury↗

PubMed1995

Free amino acids can replace protein-bound amino acids in test diets for studies in rainbow trout (Oncorhynchus mykiss).

Effects of reducing dietary concentration of protein-bound amino acids on growth, feed intake and composition of gain in rainbow trout were studied in four experiments. Average initial body weights ranged between 29 +/- 0.7 and 55 +/- 0.5 g per trout. Diets contained approximately 20 MJ digestible energy/kg dry matter. Each diet was fed to satiation to four replicate groups of 20 trout. Feed intake and growth rates were recorded for each group. Body composition was analyzed in representative groups at the start of each experiment and in all experimental groups at the end of each experiment. Reduction of dietary protein concentration to < 380 g/kg dry matter caused significantly lower growth rates and reduced protein concentrations of gain, but these reductions in growth could be offset by the addition of 10 crystalline essential amino acids. Fish meal was completely replaced by a mixture of wheat gluten and crystalline amino acids without negative influences on growth. In the absence of fish meal, almost half the wheat gluten could be replaced by crystalline amino acids in diets containing about 32 g N x 6.25/kg dry matter without significant influences on growth. In such diets, concentrations of individual amino acids may be varied widely with no variation in other amino acids or nutrients.

Amino Acids↗

PubMed1995

Response of rainbow trout (Oncorhynchus mykiss) growing from 50 to 150 g to supplements of DL-methionine in a semipurified diet containing low or high levels of cystine.

We studied the effect of increasing dietary concentrations of DL-methionine on growth, feed intake, feed conversion ratio and the composition of gain in rainbow trout. Twenty-four groups of 20 trout initially weighing 51 +/- 0.5 g/trout were fed semipurified diets containing 20.1 MJ digestible energy and either 3.0 or 5.8 g cystine/kg dry matter. At each level of cystine, 12 levels of methionine (2 to 11 g/kg dry matter) were achieved by supplementation with graded quantities of DL-methionine. During an experiment of 49 feeding days, no significant effect of the level of dietary cystine was found for any performance trait. Nonlinear responses to increasing dietary methionine concentrations were found for feed intake, growth rate, protein concentration of gain and protein deposition, whereas fat concentration of gain decreased concurrently. Dietary methionine was utilized most efficiently at a concentration of 3.5 g methionine/kg dry matter or 0.17 g/MJ digestible energy. Ninety-five percent of the plateau deposition of body protein was achieved at a dietary methionine concentration of 8 g/kg dry matter or 0.40 g/MJ digestible energy. For achieving 98%, the required concentration was 9.0 g/kg or 0.49 g/MJ. Recommended dietary methionine concentration will depend on the trait chosen.

Animal Feed↗

PubMed1995

Response of rainbow trout (Oncorhynchus mykiss) growing from 50 to 170 g to supplements of either L-arginine or L-threonine in a semipurified diet.

We studied the effects of increasing dietary concentrations of either L-arginine or L-threonine on growth, feed intake, feed conversion ratio and composition of gain in rainbow trout. Semipurified diets containing 20.1 MJ digestible energy/kg dry matter, with wheat gluten and crystalline amino acids as sole sources of amino acids, were fed to rainbow trout (initial mean body weight 47 +/- 0.7 g). In one series of 12 diets, arginine concentration ranged from 5.0 to 23.8 g/kg dry matter; in a second series of 12 diets, threonine concentration ranged from 3.7 to 21.0 g/kg dry matter. Each diet was fed to a group of 20 fish. During the experiment of 51 feeding days, dry matter intake, weight gain, feed conversion ratio, protein concentration of gain and total protein deposition followed exponential functions. For achieving 95% of the potential maximum protein deposition, dietary concentrations of 11.6 g arginine and 10.4 g threonine/kg dry matter were required. Arginine and threonine were both utilized most efficiently at dietary concentrations of approximately 6 g/kg dry matter. At low dietary concentrations of arginine, deposition of this amino acid exceeded the quantity fed. Recommended dietary concentrations of arginine and threonine will depend on the trait desired in the trout.

Animal Feed↗

PubMed1995

Culture of bladder epithelium from cystoscopic biopsies of patients with interstitial cystitis.

Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain and urinary frequency and urgency. The epithelium may be critical in its pathogenesis; the hallmarks of the disease are visible epithelial defects (Hunner's ulcers and epithelial ruptures). Areas denuded of epithelium are commonly seen, and defects in epithelial permeability are characteristic. We report here the culture and characterization of epithelial cells from cystoscopic bladder biopsies obtained from 7 female patients with interstitial cystitis. Within 4 to 14 days cellular outgrowths appeared from explants incubated in cell medium. Monolayers reached confluence after 6 weeks. Cells of the monolayer were cytokeratin-positive and smooth muscle actin-negative, confirming their epithelial origin. They exhibited epithelial cell ultrastructure including intermediate filaments and junctional complexes. Vesicles bounded by a trilaminar plasma membrane and lateral interdigitations were also present. This is the first report of the culture of bladder epithelium from interstitial cystitis patients. Epithelial cells may be targets for initiating agents and inflammatory effects of interstitial cystitis and should be useful for studies of the pathogenesis of this disease.

Adult↗

PubMed1995

Magnesium deficiency in critically ill patients.

A study was performed to assess the value of estimation of intracellular magnesium in peripheral blood cells (red and mononuclear blood cells) in critically ill patients as an index of tissue magnesium content. A magnesium loading test was used to diagnose magnesium depletion in 16 critically ill patients. Patients were divided into magnesium depleted and non-depleted groups according to their response to the loading test. Pre-infusion plasma and intracellular (blood cell) magnesium levels were measured. There were no significant difference between the magnesium depleted (mean plasma magnesium 0.81 mmol.l-1, red blood cell magnesium 2.34 mmol.l-1, mononuclear blood cell magnesium 25.16 mmol.kg-1 dry weight) and non-depleted groups (mean plasma magnesium 0.90 mmol.l-1, red blood cell magnesium 2.18 mmol.l-1, mononuclear blood cell magnesium 18.1 mmol.kg-1 dry weight). We conclude that the diagnosis of magnesium depletion cannot be excluded in the face of normal plasma, red blood cell or mononuclear blood cell concentrations of magnesium.

Critical Illness↗

PubMed1995

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer.

Thirteen postmenopausal women with advanced breast cancer were enrolled in an open randomized Phase I trial of a new p.o. active aromatase inhibitor, CGS 20267 (letrozole). The primary aim of the trial was to assess the impact of two doses of letrozole (0.5 and 2. 5 mg/day) on the peripheral aromatization of androstenedione to estrone. An in vivo isotopic technique was used to measure peripheral aromatization in each patient before treatment. The patients were then randomly assigned to one of the two doses, and measurements of aromatization were repeated after 6 weeks. At 0.5 mg and 2.5 mg/day, letrozole inhibited aromatization by 98.4% (97.3 to >99.1) and >98.9% (98.5 to >99.1; geometric means and ranges), respectively. Plasma estrogen levels were also measured before and during treatment. At the dose of 0.5 mg/day estrone and estradiol levels fell by 82.0% and 84.1% (geometric means), respectively. At the dose of 2.5 mg/ day, the estrogens fell by 80.8% and 68.1%, respectively. There were no significant differences between the doses in aromatase inhibition. No formal statistical analysis was performed on the estrogen data. Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated. The falls in estrogen levels were greater than those seen with earlier generation aromatase inhibitors.

Adult↗

PubMed1994

Clinical and endocrine effects of the oral aromatase inhibitor vorozole in postmenopausal patients with advanced breast cancer.

Vorozole is an orally active, nonsteroidal aromatase inhibitor. Twenty-four postmenopausal patients with advanced breast cancer who had relapsed after treatment with tamoxifen received three separate daily doses of vorozole (1, 2.5, and 5 mg) each for 1 month in a randomized, double-blind, phase II study. There was significant suppression (P < 0.001) of serum estradiol at all three doses (median reduction, 91, 90, and 89%, respectively). There was a significant trend (P = 0.02) for estradiol to be suppressed below the detection limit of the assay (3 pmol/liter) more frequently with an increasing dose of vorozole; 13, 31, and 40% respectively. Estrone and estrone-sulfate levels were likewise reduced at each dose by 52-55% and 64-69%, respectively. There was no significant effect at any dose on aldosterone, testosterone, androstenedione, 17 alpha-hydroxyprogesterone, or thyroid-stimulating hormone levels. A small reduction in cortisol was seen at the 5 mg dose, although the relevance is unclear given that 17 alpha-hydroxyprogesterone levels did not rise. Eight patients (33%) achieved an objective response (2 complete remission, 6 partial remission) with a median response duration of 13 months. Four patients (17%) achieved disease stabilization for more than 6 months. Patients who had responded previously to tamoxifen were more likely to respond to vorozole. There were no significant clinical side effects and the drug was well tolerated. These data suggest that vorozole is a potent and selective oral aromatase inhibitor for use in postmenopausal breast cancer.

Aged↗

PubMed1994

Comparative assessment of DNA analysis in effusions by image analysis and flow cytometry.

Cytologic evaluation of body cavity fluids is useful to detect malignancy within the pleural and peritoneal spaces. A definitive diagnosis cannot always be made on cytologic evaluation alone. As malignant processes may show abnormal DNA content, DNA analysis of effusions may be useful. Therefore, we determined the DNA content of 37 effusions by flow cytometry (FC) and image analysis (IA) using the CAS 200. Of the 37 fluids evaluated, 18 were cytologically malignant, 15 benign, and four atypical. Overall, 22 fluids (60%) showed concordance between FC and IA. None of the benign fluids were aneuploid. All showed diploid histograms or diploidy with increased proliferating cells. Three of four atypical fluids had increased proliferating cells by either FC or IA, whereas one was diploid by both methods. Aneuploidy was detected in 13 malignant fluids: five were aneuploid by both methods and eight by only one method. IA identified aneuploidy in five of those eight cases, while three were identified by FC. Three of the cytologically malignant fluids were diploid by both methods, and two showed increased proliferating cells by IA and diploidy by FC. The specificity of both methods was 100%. However, the sensitivity of identifying a malignant fluid by aneuploidy is low, 44% for FC and 55% for IA. IA appears to identify small aneuploid populations more frequently than FC. The detection of aneuploidy in effusions is highly suggestive of malignancy, and the combination of both techniques gives the highest detection rate (72%). However, neither are as sensitive as traditional cytologic evaluation with the occasional use of additional histochemical stains.

DNA, Neoplasm↗

PubMed1994

A prospective study of widowhood and changes in symptoms of depression in a community sample of the elderly.

This survey examines changes in depressive symptomatology (CES-D) during bereavement in 1046 elderly subjects, of whom 139 became widowed during follow-up. Depression scores increased during the first year of bereavement, but generally returned to pre-widowhood levels thereafter. However, depression scores remained elevated among young-old widows (65-74-year-olds) well after the first year of widowhood. Using cut-off scores, rates of high depressive symptoms remained somewhat elevated over baseline levels. Increases in depression scores during bereavement were not explained by socio-economic variables, health habits and health status. It is concluded that particularly young-old widows are at risk of developing chronic depressive symptomatology during bereavement that may warrant clinical attention.

Adaptation, Psychological↗

PubMed1994

Combined treatment with 4-hydroxyandrostenedione and aminoglutethimide: effects on aromatase inhibition and oestrogen suppression.

The effects of a combination of aminoglutethimide (AG) 1,000 mg daily and 4-hydroxy-androstenedione (4OHA) 500 mg i.m. weekly on peripheral aromatase activity as measured by in vivo radioisotopic tracer methodology and serum oestrogen suppression were investigated in ten post-menopausal women with advanced breast cancer. Patients were treated for a minimum of 4 weeks with 4OHA before addition of AG for a minimum of 6 weeks. Aromatase inhibition was found to be nearly identical in the two treatment situations (92.5 +/- 4.7% and 93.8 +/- 3.8% respectively). There was no further significant suppression of plasma oestradiol or plasma oestrone levels when AG was added to 4OHA treatment (mean decrease of 7.6 +/- 12.1% and 2.8 +/- 12.0% respectively). In contrast, adding AG caused a further suppression of plasma oestrone sulphate (Oe1S) compared with 4OHA monotherapy (mean suppression of 35.2 +/- 9.1%, P < 0.025). This effect on Oe1S may be due to an influence of AG on oestrogen metabolism.

Adult↗

PubMed1994

Validation of a croup score and its use in triaging children with croup.

The Syracuse croup scoring system was validated in 165 children with croup who were admitted to an intensive therapy unit for assessment over a one year period. The unit served as a croup triage point for Cardiff and its environs. A score of > 5 was taken as an indication that a patient was at risk of upper airway obstruction and was used to support a triage decision by the junior hospital doctor to admit a patient to the intensive therapy unit. All patients with an initial score < or = 5 were considered safe for transfer to a general paediatric ward and none of these required subsequent admission to intensive care. This score was then tested on a further 134 children with croup, in order to identify those patients who required specialised monitoring, observation or treatment in intensive care. A score of > 5 gave a specificity of 100% and a sensitivity of 80%. Croup scoring continued after admission on the general paediatric wards. Two patients who were originally admitted to the intensive therapy unit with a score > 5 improved within 6 h and were transferred to the general ward with a score < or = 5. These children subsequently required readmission to the intensive therapy unit. Our tracheal intubation rate of 2% was low and may relate to the routine use of regular adrenaline nebulisation. We recommend this scoring system to other paediatric departments for initial triaging decisions and for documenting progress on the wards.

Child↗

PubMed1994

G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation: safety, kinetics of mobilization, and composition of the graft.

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) makes the general anaesthesia of the donor unnecessary and may result in more rapid engraftment and faster recovery of the immune system. We have studied G-CSF-mediated PBPC mobilization in healthy donors and analysed the cellular composition of the resulting PBPC grafts. PBPC grafts were obtained from nine healthy donors (18-67 years old) for allogeneic or syngeneic transplantation. Six donors received 10 micrograms/kg G-CSF per day, the others 5-6 micrograms/kg. Mobilization and harvesting were well tolerated except for moderate bone pain which occurred in all donors primed with 10 micrograms/kg. With 10 micrograms/kg, a 31-fold (9-62) enrichment of circulating CD34+ cells was observed with peak values constantly occurring on day 5 after the start of G-CSF administration. Starting harvest on day 5, one to three collections on consecutive days yielded 5.5 x 10(6)/kg (0.9-10.7) CD34+ cells, 219 x 10(6)/kg (106-314) T cells, and 34 x 10(6)/kg (23-67) NK cells per 10 litres leukapheresis volume. Altogether, PBPC grafts contained 3 times more CD34+ cells, 7 times more T cells, and 20 times more NK cells than five allogeneic marrow grafts that were analysed for comparison. The yield of CD34+ cells per 10 litres apheresis volume as well as the height of the CD34+ peak in peripheral blood were inversely correlated to the age of the donor. In the donors primed with 5-6 micrograms/kg G-CSF the increase of circulating CD34+ cells (4-7-fold enrichment) and the CD34+ cell yield per 10 litres leukapheresis volume (1 x 10(6)/kg [0.8-2.2]) was much smaller compared with the 10 micrograms/kg group. In conclusion, sufficient amounts of PBPC capable of restoring haemopoiesis in allogeneic recipients can be mobilized safely by administration of G-CSF (10 micrograms/kg s.c. for 5 d) in healthy donors, and harvested with one or two leukapheresis procedures. Whether the large numbers of T-cells and NK cells that are contained in the collection products may influence graft-versus-host and graft-versus-leukaemia reactivities of PBPC grafts remains to be determined.

Adolescent↗