The current and future role of the Internet in patient education

The Internet technology known as the World Wide Web is rapidly emerging as the most powerful medium of mass communication this century and it can be harnessed to dispense global, cost-effective, high-quality, multimedia patient education material. This paper reviews how the Internet has progressed from delivering simple static, text-based material to sophisticated interactive Web sites based on CGI Technology. Interactive Web sites can be used to deliver health assessment questionnaires and Web-based decision-support systems can give patients advice on the emergency management of acute medical problems. The advantages and drawbacks of this new technology, including information regulation and quality are discussed. The role of the Hospital Intranet as a patient education resource is described. The paper concludes by illustrating how patients can appreciate the 3-D structure of bones and organs using virtual reality in a VRML Web environment.     

An evaluation of ruminally degradable intake protein and metabolizable amino acid requirements of feedlot calves

Ruminally degradable intake protein (DIP) and metabolizable indispensable amino acid (MIAA) requirements of feedlot steers were evaluated. Dietary treatments consisted of isocaloric 80% concentrate steam-flaked corn-based diets containing either .8% urea, 1.5% fish meal (FM), 3.0% FM, 4.5% FM, or 4.5% soybean meal (SBM). Treatment effects on characteristics of ruminal and total tract digestion were evaluated using four Holstein steers (249 kg) with cannulas in the rumen and proximal duodenum. Ruminal digestibility of OM (RDOM; P < .05) and feed N (P < .01) and microbial N flow (MNF; P < .01) to the small intestine were greater with urea as the supplemental N source. The level of DIP was closely associated (R2 = .89) with MNF. Postruminal digestibility of OM was greater (P < .05) for FM than for urea-supplemented diets, compensating for lower RDOM. There were no treatment effects (P > .10) on DOM. As the level of FM was increased, MIAA increased linearly (P < .01). Intestinal MIAA were similar (P > .10) for urea- and SBM-supplemented diets. Treatment effects on 56-d growth performance were evaluated using 100 medium-framed crossbred steers (231 kg). Daily weight gain (linear effect; P < .01), DM intake (linear effect; P < .10), feed efficiency (linear effect; P < .05), and diet NE (linear effect; P < .05) increased with level of FM supplementation. Daily weight gain (P < .10) and DM intake (P < .05) were greater for urea- than for SBM-supplemented diets. Using bovine tissue as the reference protein, the biological value (based on chemical score) of the intestinal chyme protein averaged 73%; methionine was first-limiting. There was a close association (R2 = .99) between methionine supply to the small intestine and observed/expected dietary NE. The metabolizable methionine requirement (MMETR, g/d) of medium-framed feedlot steers can be reliably predicted from measures of BW and ADG (MMETR = 1.565 + .0234ADG[268 - (29.4 x .0557BW(.75)ADG(1.097))/ADG] + .0896BW(.75)). There was a very close association (R2 = .89) between DIP and MNF (MNF = 13.7DIP - .66DIP(2) + 25.9). At maximal observed synthesis, DIP accounted for 76% of the MNF. A minimum of 100 g DIP/kg of total tract digestible OM was required to maximize RDOM and MNF.     

Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1

Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for degradation, and that substrate specificity is likely to be mediated by the F-box subunit. A screen for genetic interactions with a cdc34 mutation yielded MET30, which encodes an F-box protein. MET30 is an essential gene required for cell cycle progression and met30 mutations interact genetically with mutations in SCF components. Furthermore, physical interactions between Met30, Cdc53, Cdc34, and Skp1 in vivo provide evidence for an SCFMet30 complex. We demonstrate the involvement of Met30 in the degradation of the Cdk-inhibitory kinase Swe1. Swe1 is stabilized in met30 mutants and GST-Met30 pull-down experiments reveal that Met30 specifically binds Swe1 in vivo. Furthermore, extracts prepared from cdc34 or met30 mutants are defective in polyubiquitination of Swe1. Taken together, these data suggest that SCF-mediated proteolysis may contribute to the regulation of entry into mitosis. Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity.     

Altered properties of the branched chain amino acid-preferring activity contribute to increased cleavages after branched chain residues by the "immunoproteasome"

The multicatalytic proteinase complex (MPC, proteasome) is assembled from 14 nonidentical protein subunits. It expresses five distinct proteolytic activities, including a chymotrypsin-like activity, cleaving after hydrophobic residues, and a branched chain amino acid-preferring component (BrAAP), cleaving preferentially after branched chain residues. Exposure of cells to interferons leads to replacement of the X, Y, and Z subunits by the LMP2, LMP7, and MECL1 subunits. This "immunoproteasome" is critical to processing of certain antigens. The enzymatic basis for enhanced antigen processing has not been determined. To gain insight into this question, we examined sites and relative rates of cleavage of bonds in denatured, reduced, carboxyamidomethylated lysozyme, a 129-amino acid protein, by MPC from bovine spleen, in which the X, Y, and Z subunits are replaced by LMP2, LMP7, and MECL1. We compared cleavages to those catalyzed by MPC from bovine pituitary, which contains only the X, Y, and Z subunits. We found marked increases in the rates and number of cleavages after branched chain residues in reduced, carboxyamidomethylated lysozyme by the spleen MPC. This was largely due to accelerated cleavages of bonds after a Phi-X-Br motif, where Phi is a hydrophobic residue, X is a small neutral or polar residue, and Br is a branched chain residue. Inhibitors with these structural properties were selective and potent inhibitors of the BrAAP activity of the spleen MPC. The above findings indicate that alterations in activity and substrate specificity of the BrAAP activity are important factors underlying the altered cleavages after hydrophobic residues associated with incorporation of interferon-inducible subunits. The potential relevance of the findings to antigen processing functions of MPC is discussed.     

Halitosis and Helicobacter pylori: a possible relationship

With the aim of investigating a possible relationship between "objective" halitosis (established by sulfide levels in the breath) and Helicobacter pylori, we performed a study in 58 dyspeptic patients reported to suffer from "bad breath." Furthermore, we evaluated the effects on halitosis of eradication therapy (only for H. pylori-positive patients) and chlorhexidine antiseptic mouth rinses (in all patients). Sulfide compound assay indicated objective halitosis in 52/58 patients, 30 of whom were positive and 22 negative for H. pylori. In 19/30 eradication by double therapy provoked a decrease to below the cutoff value of sulfide levels in 15. In the other 11 of the 30 subjects, in whom H. pylori positivity persisted, halitosis parameters did not change. Chlorexidine reduced sulfides to below the cutoff value in 16/22 H. pylori-negative patients, but did not provoke any change in the 11 unsuccessfully treated H. pylori-positive subjects. In these, objective halitosis disappeared only after a successful eradication by triple therapy (9/11). Our results show a possible association between halitosis and H. pylori since bacterial eradication may resolve the symptom. Antiseptic mouthwashes may be effective only in absence of H. pylori, when halitosis may be due to oral putrefactive microbial activity. In a small number of subjects the cause and treatment of halitosis need to be clarified.     

Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism

Heterozygous mutations in the gene for the Kit transmembrane receptor have been identified recently in human piebaldism and mouse "dominant spotting." Interestingly, all of the 14 known missense mutations that cause depigmentation in these species map to the tyrosine kinase domain of the receptor, whereas none have involved the extracellular ligand-binding domain. In an attempt to detect these uncommon mutations, we screened the nine exons encoding the extracellular portion of Kit for single-strand conformation polymorphisms (SSCP) in eight piebald subjects previously reported to be negative for kinase mutations. Four of these eight kindreds proved to carry novel mutations. The first mutation, found in two apparently unrelated probands with mild piebaldism and English ancestry, substitutes an arginine for a highly conserved cysteine at codon 136. This substitution disrupts a putative disulfide bond required for formation of the second Ig-like (D2) loop of the Kit ligand-binding domain. The second mutation, detected in a piebald kindred characterized by unusually limited depigmentation, substitutes a threonine for an alanine at codon 178, a site just proximal to conserved cysteines at codons 183 and 186. The third mutation, occurring in a kindred with more extensive depigmentation, is a novel four-base insertion in exon 2 that results in a proximal frameshift and premature termination. The data strongly suggest that piebaldism can result from missense mutations in the Kit ligand-binding domain, although the resulting phenotype may be milder than that observed for null or kinase mutations. The apparent clustering of these uncommon mutations at or near the conserved cysteines for the D2 Ig-like loop further suggests a critical role for this region in Kit receptor function.     

Ambulatory urodynamics: extramural testing of the lower and upper urinary tract by Holter monitoring of cystometrogram, uroflowmetry, and renal pelvic pressures

This article elucidates the clinical applicability and state of the art of ambulatory urodynamics. Ambulatory urodynamics have evolved into practical investigations like EAC, HFM, and EAC combined with renal pelvimetry. EAC has been shown to be the method of preference if detrusor overactivity is involved. Conventional filling cystometry has proved to be an unreliable way to exclude detrusor instability. De novo instability after suspension surgery often indicates that an existing detrusor overactivity was not identified preoperatively. EAC including flowmetry has shown considerable variance in obstructive and contractility parameters in males with LUTS indicative for BPH. This raises doubt whether the clinical flow analysis is the suitable "gold standard" as advocated by the ICS. For a real break through of EAC, less complex automatic analysis is necessary. HFM is a newer method within the range of ambulatory urodynamic tests. It has not yet been completely evaluated. But, because the technique is analogous to the office flowmetry, noninvasive and very well accepted by the patients, it is expected to be widely used. This expectation is strengthened by the fact that HFM seems to show individual therapeutic efficacy of drugs, such as alpha-blockers. As a research tool to evaluate efficacy, it is far more powerful than conventional methods because of the reduction of within-patient standard deviation to about 10%. Finally, EAC combined with pelvimetry offers a promising method for the clinical evaluation of a combined dysfunction of upper and lower urinary tract.