The prevention of cancer

The purpose of this review is to summarize recent functional and structural findings regarding non-collagenous matrix proteins in bone and teeth, to compare gene locations for bone and tooth matrix proteins with loci for hereditary skeletal diseases, and to present several provocative hypotheses which integrate this new information into a physiological context. Hypothesis I proposes that the molecular composition of rapidly deposited and mineralized woven bone, as well as the responsiveness of cells synthesizing woven bone to stimuli, is different from that for more slowly synthesized lamellar bone, implying the existence of distinctive osteogenic mechanisms. This review of recent research strongly supports this proposal. Briefly, the protein composition of woven bone matrix is enriched in acidic phosphoproteins BAG-75 and BSP, which are not expressed in lamellar bone, which is itself enriched in osteocalcin. De novo deposition and mineralization of woven bone occurs faster than in lamellar bone by means of a matrix-vesicle-assisted mechanism. Deposition of woven bone occurs at sites experiencing biomechanical strains higher than those experienced by lamellar bone. In addition, woven bone in metaphyseal regions is more susceptible to osteoclastic resorption after space flight, ovariectomy, and loss of weightbearing than is lamellar bone. Finally, osteoprogenitor cells responsive to parathyroid hormone reside in the metaphyseal region of long bones. Taken together, these findings suggest that Hypothesis I represents a useful paradigm for future studies. Specific functions mediated by most individual bone and tooth matrix proteins remain uncertain. A review of current literature suggests that the functionality of skeletal matrix proteins is expressed through specific binding sites composed of particular species-conserved structural motifs (Hypothesis 2). Examples include the previously recognized Asp-Ser-Ser motif of dentin phosphophoryns and the gamma-carboxyglutamic acid motif of matrix GLA protein and osteocalcin. A new polyacidic amino acid motif composed of consecutive Asp and Glu residues (n > 7) was defined in extracellular matrix components osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 on the basis of strong functional analogies with similar polyacidic stretches in divalent metal storage proteins of the endoplasmic reticulum and sarcoplasmic reticulum. These structural motifs represent prime targets for future structure-function studies in vivo and in vitro.     

Diagnosis of renovascular disease by extra- and intrarenal Doppler parameters

It is still a matter of debate as to which parameters should be used for noninvasive diagnosis of renovascular disease by renal Doppler sonography (RDS). The accuracy of RDS in the detection of renal artery stenosis (RAS) was tested in 95 consecutive, moderate to severe hypertensive patients (I-II World Health Organization [WHO] stages). Reno-aortic ratio (RAR) for peak systolic velocity (PSV) was also calculated to assist in the diagnosis of significant (>50%) RAS. Paired receiver-operating characteristic (ROC) analysis was plotted for evaluating the relationship between sensitivity and specificity for each parameter. In a subset of 57 kidneys, the influence of blood pressure and age on intraparenchymal parameters was evaluated. Measurements of maximal peak systolic velocity (PSV) at the site of stenosis, RAR for PSV, and minimum acceleration index in the main renal artery showed high accuracy (areas under the ROC curve 0.97, 0.88, and 0.80, respectively). Among intraparenchymal parameters, early systolic acceleration showed the best area under the ROC curve (0.90), but provided a low positive predictive value (29%) and was significantly influenced by blood pressure (multiple r=0.56; p=0.001). Pulsatility and resistive indices were found to be less powerful as absolute values, and both significantly influenced by blood pressure and age (multiple r=0.60 and 0.50; p=0.001, p=0.02, respectively). However, interindividual variance of intrarenal indices should be minimized by calculation of side difference, although this procedure would become misleading or impossible in patients with bilateral RAS or a single kidney, respectively. These results support the use of extraparenchymal parameters for noninvasive detection of RAS, and emphasize that intrarenal parameters cannot be considered as absolute values.     

Growth-inhibitory activities of benzofuran and chromene derivatives toward Tenebrio molitor

Growth-inhibitory activities of selected natural benzofurans (4-9), trans-cinnamic acid derivatives (10-13), chromene compounds (14 and 16), and some semisynthetic derivatives were determined in last instar larvae of Tenebrio molitor via topical administration in Me2CO. The most inhibitory of the tested compounds were 3-gamma, gamma-dimethylallyl-p-coumaric acid (10) and the benzofuran derivative 12-(p-cumaroyloxy)-tremetone (5), the former compound acting on the pupae and the latter on the last instar larvae. Several developmental deficiencies were observed, and some structure-activity relationships are discussed.     

Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator?

Several endogenous oscillators determine circadian rhythms. One, light-entrained, is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and feeding affect rhythms, we compared nocturnally active rats fed either ad libitum or for 2 hr/d during light [restricted feeding (RF)] and either with or without colchicine-induced disruption of VMN. We measured rhythms in temperature, locomotor activity, feeding, drinking, corticosterone, and the numbers of cells expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN, whereas the VMN and sPVNz lacked light/dark differences except after RF and RF plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere maintaining dark > light. By contrast, levels of corticosterone peaked before food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos activity driven by the SCN. The VMN may contain a food-entrained oscillator, and the sPVNz may integrate output from several oscillators.     

Health economics and cost implications of anxiety and other mental disorders in the United States

BACKGROUND: Mental disorders impose a multi-billion dollar burden on the economy each year; translating the burden into economic terms is important to facilitate formulating policies about the use of resources. METHODS: For direct costs, data were obtained from national household interview and provider surveys; for morbidity costs, a timing model was used that measures the lifetime effect on current income of individuals with mental disorders, taking into account the timing of onset and the duration of these disorders, based on regression analysis of Epidemiologic Catchment Area study data. RESULTS: The total economic costs of mental disorders amounted to US$147.8 billion in 1990. Anxiety disorders are the most costly, amounting to $46.6 billion, or 31.5% of the total; schizophrenic disorders accounted for $32.5 billion, affective disorders for $30.4 billion, and other mental disorders for $38.4 billion. CONCLUSIONS: Mental illnesses, especially anxiety disorders, are costly to society. Although anxiety disorders have a higher prevalence than affective disorders and schizophrenia, use of medical care services is lowest for anxiety disorders. Anxiety disorders appear to be under-recognised and untreated even though treatment interventions have been shown to be effective and can be delivered in a cost-efficient manner.     

Management of nevus spilus

BACKGROUND: Granulomatous gastritis is a rarely observed pathological diagnosis. This condition often mimics gastric adenocarcinoma clinically, resulting in gastric resection. However, granulomatous gastritis has long been viewed as a benign process not observed in association with adenocarcinoma of the stomach. This article describes a patient with granulomatous gastritis occurring in close proximity to an area of superficially invading gastric adenocarcinoma. METHODS: Acid-fast stains, fungal stains, standard cultures, tuberculosis cultures, and a VDRL serum test were all obtained. Both upper endoscopy and colonoscopy were performed. Chest radiographs were taken and pulmonary consultation was obtained. RESULTS: The gastric samples obtained from resection showed no evidence of foreign body reaction. The acid-fast stains, fungal stains, cultures, and VDRL were all negative. Endoscopic exams did not show granulomatous inflammation in any other part of the gastrointestinal tract. No pulmonary disease was evident on radiographic or pulmonary exam. CONCLUSION: Isolated granulomatous gastritis is a diagnosis of exclusion. The findings in this patient do not support a diagnosis of Crohn's disease, tuberculosis, sarcoidosis, syphilis, histoplasmosis, berylliosis, or foreign-body reaction. This is a unique case suggesting an association between isolated granulomatous gastritis and metaplastic mucosal changes.     

Holtzman and Harlan Sprague-Dawley rats: differences in DRL 72-sec performance and 8-hydroxy-di-propylamino tetralin-induced hypothermia

Several compounds were tested on the differential-reinforcement-of-low-rate 72-sec (DRL 72-sec) schedule, a behavioral screen to determine putative antidepressants; these compounds were evaluated in two outbred stocks of rats, Harlan and Holtzman Sprague-Dawley rats. A dose-response determination for the tricyclic antidepressants, imipramine and desipramine, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, the 5-HT2 receptor antagonist, ketanserin, the 5-HT1A receptor agonist, (+/-)8-hydroxy-di-propylamino tetralin (8-OH-DPAT) and the dopamine releasing compound, amphetamine, were assessed in both rat stocks. The two stocks of rats differed in their baseline performance on the DRL 72-sec schedule. The Harlan rats had a higher reinforcement rate and a lower response rate than the Holtzman rats. In Holtzman, but not in Harlan rats, imipramine, ketanserin, fluoxetine and 8-OH-DPAT increased reinforcement rate and decreased response rate on the DRL 72-sec schedule, confirming previous studies. However, desipramine was the only drug to increase reinforcement rate and decrease response rate in both Holtzman and Harlan rats; in Harlan rats, drugs that primarily act upon the 5-HT system, imipramine, ketanserin, fluoxetine and 8-OH-DPAT, disrupted the DRL 72-sec performance and did not increase the number of reinforcements over baseline as was seen in Holtzman rats. Amphetamine disrupted DRL 72-sec performance in both Holtzman and Harlan rats in a similar manner. The hypothermic response to 8-OH-DPAT was also assessed in the two stocks of rats; Holtzman rats had a smaller decrease in core body temperature than Harlan rats. The observed behavioral and pharmacological differences between Holtzman and Harlan rat stocks may be genetically and/or environmentally mediated.     

Risk and protective factors for children''s substance use and antisocial behavior following parental divorce

Shape memory nickel-titanium (NiTi) alloys are potential candidates for biomedical applications. However, their equiatomic composition (50 wt% Ni) is controversial, and concerns have been raised about their biocompatibility level because of the carcinogenicity potential. The relative in vitro genotoxicity of NiTi therefore was evaluated and compared to commercially pure titanium (cpTi), 316L stainless steel (SS 316L), and positive and negative controls. To do so, human peripheral blood lymphocytes were cultured in semiphysiological medium that previously had been exposed to the biomaterials. The electron microscopy in situ end-labeling (EM-ISEL) assay then was performed in order to provide quantification of in vitro chromatin DNA single-stranded breaks (SSBs). Chromosomes and nuclei were harvested and exposed to exonuclease III, which amplifies DNA lesions at 3' ends of breaks. After random priming, incorporation of biotin-dUTP was labeled by immunogold binding, which then was detected using electron microscopy. Cellular chromatin exposed to the positive control demonstrated a significantly stronger immunogold labeling than when it was exposed to NiTi, cpTi, SS 316L extracts, or the untreated control. Moreover, gold particle counts, whether in the presence of NiTi, cpTi, or the negative control medium, were not statistically different. NiTi genocompatibility therefore presents promising prescreening results towards its biocompatibility approval.     

Suprascapular neuropathy after distal clavicle excision

Two cases of suprascapular neuropathy after excision of the distal clavicle are reported. Both patients were treated successfully with neurolysis of the suprascapular nerve starting at the upper trunk of the brachial plexus. Anatomic dissections revealed that the suprascapular nerve is quite close (<1.4 cm) to the posterior aspect of the distal clavicle, within 2 to 3 cm of the acromioclavicular joint. To avoid the complication of suprascapular neuropathy that could be associated with this close relationship, it is recommended that no more than 1 cm of the distal clavicle be removed posteriorly. It is also recommended that minimal periosteal elevation should be performed on the posteroinferior border of the distal clavicle.