Medical student attitudes and concepts of frailty and delirium.

BACKGROUND: Frailty and delirium are important conditions in an ageing population, but there is little evidence exploring medical students' conceptualisation of, or attitudes towards these subjects. We investigated how students' concepts of frailty and delirium changed following a new geriatric medicine module at Manchester medical school. MATERIALS AND METHODS: Semi-structured interviews were used with students before and after the new teaching week to explore changes in attitude towards frailty and delirium and their conceptualisation. Final year students who had not completed the module were interviewed as a comparison group. Grounded theory and content clouds were employed for data analysis. RESULTS: Ten 4th year and 11 final year students were interviewed. After the teaching week, 4th year students had a richer conceptualisation of frailty and delirium. Students described structured assessments such as comprehensive geriatric assessment and expressed confidence in their use. Their frameworks were more developed than the final year students who had not had such teaching. Attitudes towards older people, frailty, delirium, and the specialty of geriatric medicine improved following the teaching week. CONCLUSION: This study shows that geriatric medicine teaching improves students' conceptualisation of frailty and delirium and their understanding of the importance of structured assessments and management plans.

In vitro growth response of bread-spoilage Bacillus strains to selected natural antimicrobials.

This study assessed the in vitro responses of Bacillus (B.) strains isolated from ropey bread to natural antimicrobials under optimum growth conditions. The responses of six Bacillus strains [B. subtilis (2), B. licheniformis (2) and B. pumilus (2)] to acetic acid (AA), lactic acid (LA), calcium lactate (CL) and a lactate-containing cocktail (LCC), singly and in combinations were determined and compared to calcium propionate (CP). Isolates were each inoculated into flasks containing Nutrient Broth (NB) and the respective antimicrobial treatments and pHs were left unadjusted. A duplicate set of flasks, also containing NB and the respective antimicrobials, but adjusted to pH's corresponding to those of baked brown bread containing the same antimicrobials was also inoculated. Growth curves were obtained spectrophotometrically and used to estimate lag times. The organic acids used in this study [0.1% (v/v) AA and 0.25% (v/v) LA] singly and in combination with each other and with CL, CP or LCC, completely inhibited the growth of all six Bacillus strains, but only at non-adjusted pHs. The efficacies of LA, AA and CL notably decreased when the pH of the test media containing the respective preservatives was adjusted to the corresponding in situ (bread) values. However, the natural antimicrobials were still as effective as CP in retarding growth of the six Bacillus strains at the in situ (bread) pH values.

Effect of selected natural antimicrobials on Baker's yeast activity.

AIMS: To evaluate the responses of Baker's yeast (Saccharomyces cerevisiae) activity to the natural antimicrobials acetic acid, calcium lactate, a lactate-containing cocktail and lactic acid compared to calcium propionate. METHODS AND RESULTS: A dough fermentometer test was used to measure Baker's yeast activity in the presence of these natural antimicrobials and calcium propionate. Yeast activity generally decreased as a function of increasing antimicrobial concentrations, but the lactate-containing cocktail showed no relationship between concentration and yeast activity reduction. At in situ concentrations, calcium propionate resulted in the highest yeast activity reduction, followed by calcium lactate, acetic acid, the lactate-containing cocktail and lactic acid in decreasing order. CONCLUSION: Based on yeast activity reduction, all natural antimicrobials tested showed potential as possible replacements for calcium propionate. SIGNIFICANCE AND IMPACT OF THE STUDY: This has practical implications since calcium propionate inhibits Baker's yeast activity and attracts negative consumer perceptions as a chemical bread preservative.

Microbial populations associated with commercially produced South African sorghum beer as determined by conventional and Petrifilm plating.

Microbial populations of 46 commercially produced sorghum beer samples from retail outlets in Johannesburg, South Africa, were enumerated and characterized. Aerobic plate counts, lactic acid bacteria counts and yeast counts were performed by conventional and Petrifilm plating. Conventional methods yielded yeast counts of 7.84 log CFU/ml, lactic acid bacteria counts of 6.44 log CFU/ml and aerobic plate counts of 5.96 log CFU/ml. In comparison, Petrifilm counts were 7.85 log CFU/ml for yeasts, 5.31 log CFU/ml for lactic acid bacteria and 5.34 log CFU/ml for aerobic bacteria. Characterization of 419 predominant bacterial isolates from Standard One Nutrient Agar, MRS Agar and corresponding Petrifilm plates yielded 88.0% lactic acid bacteria, 8.4% Bacillus species, 2.9% Micrococcus species and 0.7% Gram negative bacteria. Composition of predominant lactic acid bacteria populations from Standard One Nutrient Agar and both types of Petrifilm plates showed marginal differences. Increased proportions of heterofermentative lactic acid bacteria were, however, isolated from conventional MRS Agar compared to the modified Petrifilm product which represented the equivalent to MRS Agar.

Upregulation of aquaporin 2 water channel expression in pregnant rats.

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.

Sarcoidal foreign-body granulomatous dermatitis associated with ophthalmic drops.

Sarcoidal granulomas are found in sarcoidosis and in reactions to foreign materials. We report the case of an 81-year-old woman with glaucoma who presented with multiple brown-black asymptomatic papules over the chin and involving nasal mucosa and columella of 1-year duration. Biopsy of the nasal mucosa and cutaneous papules showed sarcoidal granulomas associated with brown-black intracellular pigment within multinucleated giant cells. Electron-probe x-ray microanalysis demonstrated high sulfur content. Clinical studies showed no evidence of systemic sarcoidosis. Two of three ophthalmologic drops contained sodium bisulfite; bisulfite is known to cause allergic reactions. Although the exact substance causing the granulomatous reaction is unknown, the distribution of the lesions--nasal mucosa and columella (via the nasal lacrimal duct) and the underlying chin--implicate the eyedrops in the production of the pigmented granulomatous nodules.

Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.

Chronic hypoxia induces proliferation of cultured mesangial cells: role of calcium and protein kinase C.

The effect of hypoxia on the proliferation of cultured rat mesangial cells was examined. To evaluate the underlying signaling mechanisms, the roles of intracellular calcium ([Ca2+]i) and protein kinase C (PKC) were determined. Quiescent cultures were exposed to hypoxia (3% O2) or normoxia (18% O2), and [3H]thymidine incorporation, cell number, [Ca2+]i, and PKC were assessed. Mesangial cells exposed to 28 h of hypoxia exhibited a significant increase in [3H]thymidine incorporation followed by a significant increase in cell number at 72 h in comparison with respective normoxic controls. Hypoxia induced a biphasic activation of PKC, reflected by translocation of the enzyme activity from cytosol to membrane at 1 h, a return to baseline at 4 and 8 h, with subsequent reactivation from 16 to 48 h. In addition, hypoxia-induced proliferation was prevented by a PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Cells exposed to hypoxia produced progressive increases in resting [Ca2+]i from 15 to 60 min which remain sustained up to 24 h of examination. Verapamil significantly prevented the hypoxia-induced proliferation, and both verapamil treatment and incubations in a calcium-free medium for 1 h blocked the hypoxia-induced stimulation of [Ca2+]i as well as PKC. These results provide the first in vitro evidence that chronic hypoxia induces proliferation of cultured glomerular mesangial cells, which is mediated by the stimulation of [Ca2+]i and the subsequent activation of PKC.

Basic fibroblast growth factor within endothelial cells during vascularization of the anterior pituitary.

BACKGROUND: Basic fibroblast growth factor (FGF-2), a potent angiogenic peptide, is known to be present in gonadotropes of the anterior pituitary parenchyma of rats and mice, and has been isolated from endothelial cells of many organs. Its localization within endothelial cells has not been determined, nor the mechanisms by which it might be released from endothelial cells during normal organogenesis. METHODS: Localization of FGF within endothelial cells of the anterior pituitary was accomplished by immunocytochemistry and studied by light- and electron microscopy. Capillaries within the anterior pituitary were studied in fetal rats from day 15 to term, and in adult rats. RESULTS: At the onset stages of vascularization (15-18 days fetal), the cytoplasm of the endothelial cells of many of the invading, immature capillaries (thick-walled with few or no fenestrations) was intensely immunopositive for FGF. Immunoprecipitate-filled blebs and slender cytoplasmic processes projected from the endothelial cells into the presumptive pericapillary space and toward the parenchymal cells. As gestation progressed (19-20 day fetal), and an increasing number of capillaries acquired the features characteristic of capillaries in the anterior pituitary of adult animals, i.e., thin-walled and fenestrated, there were fewer capillaries demonstrating immunopositivity for FGF. Foci of released FGF, i.e., extracellular, were occasionally evident within the presumptive pericapillary spaces throughout gestation. By comparison, capillaries of the anterior pituitary of adult rats did not contain immunostainable FGF in their cytoplasm, nor were any blebs and/or processes filled with immunoprecipitate evident. However capillaries did reveal an immunopositive enhancement of their lumenal and ablumenal surfaces. CONCLUSIONS: During vascularization of the anterior pituitary, FGF within the cytoplasm of endothelial cells is released from blebs and/or processes of endothelial cells, and after the capillary bed is stabilized postnatally, these characteristics of vascularization are absent.

Development of the vasculature of the anterior pituitary: ontogeny of basic fibroblast growth factor.

This study correlates the ontogeny of basic fibroblast growth factor (FGF) with the development of the vasculature of the anterior pituitary (AP) in two strains of rat, Sprague-Dawley (SD) and Fischer 344 (F344). Immunolocalization of FGF was followed from the first appearance of Rathke's pouch (RP) in 12-day (12d) fetuses, through each day of fetal development, and in 5, 20, and 50d postnatal female rats. In addition, the ontogeny of folliculo-stellate cells (FSC) is described, since previous studies suggested that these unique cells might function as phagocytes in the regulation of FGF. In both rat strains, vascularization of the AP commenced in 16d fetuses. In 15-20d fetuses, dense foci of immunopositivity for extracellular FGF were apparent at sites of capillary penetration adjacent to partially disrupted, immature gonadotropes. Localization of FGF was first detected in immature gonadotropes in 18d fetuses and persisted in the cytosol of a subpopulation of gonadotropes thereafter. In 15d fetuses, FGF was localized within the cytosol intimately associated with the peripheral-facing plasma membranes of all cells of the adenohypophysis, and persisted to variable degrees in later fetal stages. Localization of FGF within nuclei of AP parenchymal cells was evident only in 16-17d fetuses. Although the ontogeny of FGF and vascularization of the AP was very similar in both rat strains, the ontogeny of FSC differed markedly. In both strains, follicular lumens contained FGF during late fetal and early postnatal development. However, both electron microscopy and immunostaining for S-100 marker protein revealed that the postero-lateral edges of the AP of F344 rats often lacked FSC when compared to SD rats, a situation which could compromise regulation of FGF by FSC at the AP periphery in that strain, and thereby contribute to the neovascularization from systemic blood vessels known to occur in that strain during prolactinoma formation.

Neural network for quadratic optimization with bound constraints.

A recurrent neural network is presented which performs quadratic optimization subject to bound constraints on each of the optimization variables. The network is shown to be globally convergent, and conditions on the quadratic problem and the network parameters are established under which exponential asymptotic stability is achieved. Through suitable choice of the network parameters, the system of differential equations governing the network activations is preconditioned in order to reduce its sensitivity to noise and to roundoff errors. The optimization method employed by the neural network is shown to fall into the general class of gradient methods for constrained nonlinear optimization and, in contrast with penalty function methods, is guaranteed to yield only feasible solutions.

Relaxation network for Gabor image decomposition.

The so-called "simple cells" in layer IV of feline primary visual cortex have been shown to have Gabor function spatial receptive field profiles (RFP's). Since Gabor functions are not mutually orthogonal, the decomposition of an image into Gabor function coefficients is usually performed by minimising some measure of the error between the original image and that reconstructed from the coefficients. A cortical relaxation model is proposed which performs this minimisation implicitly, and is used to examine the biological relevance and feasibility of reconstruction error minimisation.

Pars distalis vasculature: Discovery Shuttle STS-29 rats compared to ground-based antiorthostatic rats.

The anterior pituitary glands of male, adult Long Evans rats carried 5 days in the Space Shuttle Discovery (STS-29) have been compared with two groups of ground-based controls. All of the animals were part of a study (SE82-08) into the effects of gravity versus a microgravity environment on fracture healing. All had sustained a right, mid-shaft fibular osteotomy. The duration of the study was 10 days, and animals in all groups were weight bearing for the 5 days prior to shuttle lift off. The three experimental groups consisted of four rats each: flight (F) and two ground-based control groups, weight bearing (WB) and suspended (S). The suspension group was in a Holton/Sweeney head-down suspension apparatus (antiorthostatic) for the final 5 days of the study. The anterior pituitary glands of F and WB rats were essentially identical. The vasculature and parenchymal cells appeared unaffected in both instances. However, the anterior pituitary glands of S rats were dramatically altered. The vasculature was widely expanded with proteinaceous deposition covering the lumenal endothelial surfaces, and entrapping numerous platelets and aggregates of red blood cells. Parenchymal cells were highly vacuolated, occasionally with membranous vacuoles, but most often revealing large, clear cytoplasmic zones unlined by any membranes. Whereas profiles of exocytosis were numerous in F rats, and present in WB rats, they were essentially absent in S rats. These results indicate that weightlessness over a 5-day flight period does not influence the structural integrity of the anterior pituitary gland and may in fact promote secretory granule release. However, the head-down tilt model, frequently used to study fracture repair under conditions that mimic weightlessness, has a profound impact on the vasculature of the anterior pituitary gland which then affects the structural and functional characteristics of the parenchymal cells.

Effect of protein dose on serum glucose and insulin response to sugars.

To clarify the effects of protein on insulin and glucose response to sugars, 14 healthy normal-weight males and females were fed test meals containing 0, 15.8, 25.1, 33.6, and 49.9 g protein along with approximately 58 g carbohydrate. Serum samples were obtained at fasting time zero and 15, 30, 60, and 120 min postprandial. Mean areas of the glucose curves above fasting decreased with increasing protein dose. Protein-containing meals produced significantly lower (p less than 0.01) areas than the protein-free meal and the relationship between blood glucose area and protein dose was significant (p less than 0.001). Protein-containing meals produced significantly greater (p less than 0.01) insulin areas compared with the protein-free meal. However, no differences in insulin areas among the protein-containing meals were observed. These data support previous studies showing a blood glucose moderating and insulin-enhancing effect of protein ingestion.

Novel 1,3-bis(aryloxy)propanes as leukotriene D4 antagonists.

The synthesis and structure-activity relationships of a number of 1,3-bis(aryloxy)propanes, which are in vivo antagonists of LTD4 in the guinea pig, are described. One of these compounds, 4 (Wy-44,329), was not only approximately equipotent with the standard 1 (FPL 55712) in the LTC4 (ID50 = 0.17 and 0.23 mg/kg iv, respectively) and LTD4 (ID50 = 0.11 and 0.15 mg/kg iv, respectively) challenge models but also possessed greater potency in the ovalbumin challenge model (ID50 = 0.47 mg/kg and 4.1 mg/kg iv, respectively) and a longer duration of action. This compound was a competitive LTD4 antagonist on guinea pig ileum (pA2 = 9.4) and possessed mediator release (rat PCA, ID50 = 0.26 mg/kg iv) and 5-lipoxygenase (IC50 = 32 microM vs. 5-HETE) inhibitory activities.

Repletion and depletion of serum alpha and beta carotene in humans with carrots and an algae-derived supplement.

A 10-day low-carotene diet phase (LCD), followed by a 7-day treatment phase (TP) and then another LCD, was adhered to by 32 adult human subjects. Serum alpha carotene (SAC) and serum beta carotene (SBC) levels were examined using HPLC and found to have decreased 44.7% and 35.8% respectively in the first LCD. Alpha and beta carotene, from algae-derived capsules and raw carrots, significantly increased SAC and SBC levels during the TP. Half-lives of SAC and SBC averaged 7.8 days and 12.4 days respectively during the two LCD. Serum vitamin A remained unchanged throughout the study.

Multivitamin-mineral supplementation: effects on blood chemistries of college-age women.

Forty-two female college students, age 18-29 yr. and consuming nutritionally balanced meals in the college cafeteria participated. Subjects discontinued all vitamin-mineral supplements (VMS) for 17 days and were randomly assigned to one of two treatments, either a placebo, or VMS supplying the United States Recommended Daily Allowance (USRDA) of all vitamins, zinc, iron, iodine, copper, and 60% of the USRDA of calcium, 50% of magnesium and 45% of phosphorus. Treatments were consumed for 77 days. Fasting pre-and post-treatment blood chemistries were compared. VMS yielded significant increases (p less than 0.05) in serum vitamin B-12 (+25.05 pg/ml), vitamin C (+0.35 mg/dl) and folate (+7.40 ng/ml). No significant changes (p greater than 0.05) in hematological or other blood chemistries were observed. Significant decreases in the number of below-normal serum indicators of vitamin status (p less than 0.05) and iron status (p less than 0.005) were seen with VMS. No significant changes were seen with placebo (p greater than 0.05).

Simultaneous determination of vitamins B1, B2, B6, and niacinamide in multivitamin pharmaceutical preparations by paired-ion reversed-phase high-pressure liquid chromatography.

A high-pressure liquid chromatographic procedure for the simultaneous determination of vitamins B1, B2, B6, and niacinamide in multivitamin pharmaceutical preparations was developed and evaluated. The method uses paired-ion reversed-phase partition chromatography for baseline separation of the four water-soluble vitamins. This method was applied to the analysis of a multivitamin and multivitamin-multimineral tablets, and a technique was developed to reduce vitamin adsorption by the minerals. The results obtained by this method were compared with those obtained by the official methods. It was concluded that this method is fast, accurate, specific, and suitable for routine quality control use.