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Biomedical subjects

S Weiner

Publications and source records attributed to S Weiner.

At least 37 records · Page 2Linked to original sources

Structure of the nacreous organic matrix of a bivalve mollusk shell examined in the hydrated state using cryo-TEM.

During mollusk shell formation, the mineral phase forms within an organic matrix composed of beta-chitin, silk-like proteins, and acidic glycoproteins rich in aspartic acid. The matrix is widely assumed to play an important role in controlling mineralization. Thus, understanding its structure is of prime importance. Cryo-transmission electron microscopy (Cryo-TEM) studies of the matrix of the bivalve Atrina embedded in vitrified ice show that the interlamellar sheets are composed mainly of highly ordered and aligned beta-chitin fibrils. The silk, which is quantitatively an important component of the matrix, could not be imaged within the sheets. Organic material was, however, observed between sheets. We infer that this is the location of the silk. As this material reveals no regular structure, we suggest that at least prior to mineralization the silk is in the form of a hydrated gel. This is supported by cryo-TEM structural observations of an artificial assembly of beta-chitin with and without silk. This view of the nacreous organic matrix significantly changes previous models of the matrix structure and hence hypotheses pertaining to the mechanisms by which mineral formation occurs.

Animals↗

On how proteins interact with crystals and their effect on crystal formation.

Formation of crystalline materials in biological environments is largely dominated by macromolecules whose complementarity to the surface structure is the basis for molecular pattern recognition. This complementarity may in turn result in regulation of crystal growth and morphology, or in induction of crystal nucleation. The conceptual framework for these effects is illustrated here using examples from biomineralization as well as by the immune responses during pathological crystallizations to crystalline antigens. Antibodies are shown to be a precious tool for discerning the fine details of the interactions between biological macromolecules and ordered molecular arrays, such as are present on the surfaces of crystals, monolayers and possibly cell membranes.

Antibodies↗

Comparison of the efficacy and safety of finasteride in older versus younger men with benign prostatic hyperplasia.

OBJECTIVES: To compare the efficacy and safety of finasteride 5 mg in older (65 years old or older) versus younger (45 to younger than 65 years old) men with benign prostatic hyperplasia (BPH). METHODS: The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men 45 to 78 years old with symptomatic BPH, enlarged prostates, and no evidence of prostate cancer. The endpoints included urinary symptoms, prostate volume, occurrence of acute urinary retention and/or BPH-related surgery, and safety. RESULTS: In both age cohorts, finasteride treatment led to a 51% reduction (P <0.001) in the relative risk for acute urinary retention and/or BPH-related surgery, a significant (P <0.001) and durable improvement in symptom score, and a significant (P <0.001) and sustained reduction in prostate volume. Within each age cohort, no significant differences were found between the placebo and finasteride-treated patients in the incidence of cardiovascular adverse events. Significant differences were evident between the placebo and finasteride groups in the incidence of the typical, known, drug-related adverse events, but no specific differences were associated with age. No drug interactions of clinical importance were observed in the finasteride-treated patients. CONCLUSIONS: The present analysis from PLESS demonstrates that in both older (65 years old or older) and younger men with symptomatic BPH and enlarged prostates, finasteride is highly effective in improving symptoms and reducing prostate volume in many men and in reducing the risk of acute urinary retention and BPH-related surgery. In addition, the safety profile of finasteride in both older and younger men is similar and no drug interactions of clinical importance were observed.

Aged↗

Maternal issues affecting the fetus.

Maternal disorders and exposures that affect fetal cardiac structure and function are reviewed, emphasizing fetal echocardiographic diagnosis and monitoring, and approaches for in utero therapy. Maternal diabetes, hyperthyroidism, lupus erythematosis, epilepsy, congenital heart disease, infections, and drug exposures are considered.

Diabetes Complications↗

Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency.

A 47-year-old man suffering from a bipolar disorder and intermittent myoglobinuria presented with acute rhabdomyolysis with renal failure after starting therapy with valproic acid. On morphological examination, skeletal muscle revealed increased lipid storage. Biochemically, decreased enzyme activity of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the lower limit was found. Genetic analysis detected the common Ser113Leu substitution on one allele of the CPT2 gene. We conclude that valproic acid should be avoided in patients with CPT type II deficiency.

Acetylcarnitine↗

"I can't afford that!": dilemmas in the care of the uninsured and underinsured.

When patients lack sufficient health care insurance, financial matters become integrally intertwined with biomedical considerations in the process of clinical decision making. With a growing medically indigent population, clinicians may be compelled to bend billing or reimbursement rules, lower standards, or turn patients away when they cannot afford the costs of care. This article focuses on 3 types of dilemmas that clinicians face when patients cannot pay for needed medical services: (1) whether to refer the individual to a safety net provider, such as a public clinic; (2) whether to forgo indicated tests and therapies because of cost; and (3) whether to reduce fees by fee waivers or other adjustments in billing. Clinicians' responses to these dilemmas impact on quality of care, continuity, safety net providers, and the liability risk of committing billing violations or offering nonstandard care. Caring for the underinsured in the current health care climate requires an understanding of billing regulations, a commitment to informed consent, and a beneficent approach to finding individualized solutions to each patient care/financial dilemma. To effect change, however, physicians must address issues of social justice outside of the office through political and social activism.

Cost Control↗

A transmission electron microscope study using vitrified ice sections of predentin: structural changes in the dentin collagenous matrix prior to mineralization.

The assembly of the collagenous organic matrix prior to mineralization is a key step in the formation of bones and teeth. This process was studied in the predentin of continuously forming rat incisors, using unstained vitrified ice sections examined in the transmission electron microscope. Progressing from the odontoblast surface to the mineralization front, the collagen fibrils thicken to ultimately form a dense network, and their repeat D-spacings and banding patterns vary. Using immunolocalization, the most abundant noncollagenous protein in dentin, phosphophoryn, was mapped to the boundaries between the gap and overlap zones along the fibrils nearest the mineralization front. It thus appears that the premineralized collagen matrix undergoes dynamic changes in its structure. These may be mediated by the addition and interaction with the highly anionic noncollagenous proteins associated with collagen. These changes presumably create a collagenous framework that is able to mineralize.

Animals↗

Effect of an antirotation resistance form on screw loosening for single implant-supported crowns.

STATEMENT OF PROBLEM: The gold screw of the single tooth implant-supported restoration has frequently been reported to exhibit the problem of screw loosening. PURPOSE: This in vitro study considered an antirotation resistance form with an increased moment arm length as a strategy to increase the net effect of the retaining screw preload. MATERIAL AND METHODS: Three groups examined included (a) standard abutments (3 mm), (b) modified standard abutments (3 mm) with 4 milled (1 x 1 mm) notches placed equidistant around the periphery, and (c) Estheticone abutments (1 mm). Crown castings of 2% gold-palladium-based alloy were made using plastic and resin patterns molded to fit inside a quarter-inch socket wrench. For testing, each specimen consisted of a 15-mm endosseous threaded implant analog, its abutment (20 N force) and crown casting (10 N force) screwed together and securely clamped in a vise. A clockwise shear (rotational) force was applied using a manual torque driver and the torque recorded to failure of the gold screw or loosening of the abutment screw. RESULTS: Analysis revealed that the dislodging force for groups (b) and (c) was similar (69.6 and 71.0 N.cm, respectively), whereas group (a) (standard implant external hex) demonstrated that the smallest moment arm required a significantly smaller dislodging force (21.3 N.cm). CONCLUSION: These findings suggest that the addition of an antirotation resistance form increased the length of the moment arm, thereby increasing the effect of preload and reducing the problem of screw loosening.

Analysis of Variance↗

Bone fractures.

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Biomechanical Phenomena↗

Bending and fracture of compact circumferential and osteonal lamellar bone of the baboon tibia.

Lamellar bone is common among primates, either in the form of extended planar circumferential arrays, or as cylindrically shaped osteons. Osteonal bone generally replaces circumferential lamellar bone with time, and it is therefore of much interest to compare the mechanical properties and fracture behavior of these two forms of lamellar bone. This is, however, difficult as natural specimens of circumferential lamellar bone large enough for standard mechanical tests are not available. We found that as a result of treatment with large doses of alendronate, the lateral sides of the diaphyses of baboon tibia contained fairly extensive regions of circumferential lamellar bone, the structure of which appears to be indistinguishable from untreated lamellar bone. Three-point bending tests were used to determine the elastic and ultimate properties of almost pure circumferential lamellar bone and osteonal bone in four different orientations relative to the tibia long axis. After taking into account the differences in porosity and extent of mineralization of the two bone types, the flexural modulus, bending strength, fracture strain and nominal work-to-fracture properties were similar for the same orientations, with some exceptions. This implies that it is the lamellar structure itself that is mainly responsible for these mechanical properties. The fracture behavior and morphologies of the fracture surfaces varied significantly with orientation in both types of bone. This is related to the microstructure of lamellar bone. Osteonal bone exhibited quite different damage-related behavior during fracture as compared to circumferential lamellar bone. Following fracture the two halves of osteonal bone remained attached whereas in circumferential lamellar bone they separated. These differences could well provide significant adaptive advantages to osteonal bone function.

Journal Article↗

Changes in marginal gap size of provisional resin crowns after occlusal loading and thermal cycling.

STATEMENT OF PROBLEM: Resin materials used for provisional crowns tend to develop enlarged marginal gaps over time. With the advent of new interim resin materials in dentistry that are used for longer clinical periods, controlled comparative analysis of the structural stability of these materials in the oral environment is required. PURPOSE: This study analyzed marginal gap size changes resulting from occlusal loading and thermal cycling and related these results to material properties. MATERIAL AND METHODS: Groups (n = 10) of provisional crowns were made using 4 resin materials (Jet-relined, Snap-relined, Snap-unrelined, Alike-unrelined). Specimens were first fabricated on a metal master die and fitted with and relined on the master die to standardize pretreatment marginal gap size. Custom die stems were fabricated from a low-fusing alloy (Cerroblend) and cemented with Tempbond cement. The samples were treated with occlusal loading (50,000 cycles, 40 N, 4 Hz) and thermocycling (8, 000 cycles, 5 degrees C to 60 degrees C). Measurements of marginal gaps were recorded before and after treatment. RESULTS: The mean changes in marginal gap sizes were Jet-relined, 152.1 microm +/- 69. 6; Snap-relined, 548.9 microm +/- 168.3; Snap-unrelined, 446.6 microm +/- 91.8; and Alike-unrelined, 43.9 microm +/- 48.7. Two-way ANOVA revealed a significant difference between groups (F=51.758, df 3,1, P</=.0001). Tukey/Kramer (P </=.01 level) indicated a significantly larger gap increase for the Snap-relined and Snap unrelined groups. CONCLUSION: There were significant differences between different brands of resin materials used for provisional crowns. Each must be evaluated individually for stability in the oral environment.

Analysis of Variance↗

The effect of a cholecystokinin agonist on masseter muscle activity in the cat.

The CCK(B) agonist, pentagastrin, has been shown to induce anxiety in human subjects. Similarly, in the cat model, pentagastrin facilitates the expression of hypothalamically activated emotional behavior. Because hypothalamically mediated emotional behavior is also accompanied by increased EMG activity in the jaw muscles, these experiments were designed to examine the combined effects of administration of pentagastrin with activation of hypothalamically mediated emotional behavior upon jaw muscle EMG activity. Electrodes were carefully lowered through previously placed guide tubes overlying the hypothalamus until a behavioral site was identified. Following the establishment of a stable threshold current for eliciting an emotional behavioral response, the skin overlying the ipsilateral masseter muscle was shaved and cleaned with alcohol, and surface electrodes were attached. The EMG was recorded, amplified, digitized, and stored in a microcomputer for analysis. Mean power frequencies (MPF) and latencies for behavior were calculated for baseline prior to infusion of all drugs. Following this, the effects of intravenous administration of pentagastrin and the CCK(B) antagonist LY288513 on the MPF were determined. The infusion of the CCK(B) agonist, pentagastrin (0.77, 1.92, and 3.84 microg/kg), decreased MPF in a time-related manner. The effects of pentagastrin 1.92 microg/kg were blocked by the CCK(B) antagonist, LY288513 (6.54 microg/kg). In addition, the infusion of LY288513 alone increased MPF. These results are surprising in that pentagastrin's anxiogenic properties would appear to make it likely to facilitate motor activity, not suppress it.

Animals↗

Lamellar bone: structure-function relations.

The term "bone" refers to a family of materials that have complex hierarchically organized structures. These structures are primarily adapted to the variety of mechanical functions that bone fulfills. Here we review the structure-mechanical relations of one bone structural type, lamellar bone. This is the most abundant type in many mammals, including humans. A lamellar unit is composed of five sublayers. Each sublayer is an array of aligned mineralized collagen fibrils. The orientations of these arrays differ in each sublayer with respect to both collagen fibril axes and crystal layers, such that a complex rotated plywood-like structure is formed. Specific functions for lamellar bone, as opposed to the other bone types, could not be identified. It is therefore proposed that the lamellar structure is multifunctional-the "concrete" of the bone family of materials. Experimentally measured mechanical properties of lamellar bone demonstrate a clear-cut anisotropy with respect to the axis direction of long bones. A comparison of the elastic and ultimate properties of parallel arrays of lamellar units formed in primary bone with cylindrically shaped osteonal structures in secondary formed bone shows that most of the intrinsic mechanical properties are built into the lamellar structure. The major advantages of osteonal bone are its fracture properties. Mathematical modeling of the elastic properties based on the lamellar structure and using a rule-of-mixtures approach can closely simulate the measured mechanical properties, providing greater insight into the structure-mechanical relations of lamellar bone.

Animals↗

Peritubular dentin formation: crystal organization and the macromolecular constituents in human teeth.

Peritubular dentin (PTD) is a relatively dense mineralized tissue that surrounds the tubules of coronal tooth dentin. It is composed mainly of crystals of carbonated apatite together with a small amount of collagen. Its mode of formation has been investigated by studying the relatively dense particles isolated from a powdered preparation. Electron microscopic examination of the PTD particles, including 3-dimensional image reconstruction and electron diffraction, shows that the organization of the crystals of PTD is very similar to that of the adjacent intertubular dentin (ITD). The latter contains relatively large amounts of collagen and the carbonated apatite crystals are closely associated with the collagen matrix. The proteins present in the PTD particles are soluble after decalcification and stain with Stains All. The principal protein has higher molecular weight and a quite different amino acid composition than the phosphophoryns of the intertubular dentin. The interface between the PTD and the ITD shows structural continuity. These data show how two distinct carbonated apatite-based mineralized tissues can be organized and formed contiguously within the same organ by utilizing different sets of matrix proteins.

Adult↗

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial.

OBJECTIVE: To test the hypothesis that systemic sclerosis (SSc) patients taking high-dose D-penicillamine (D-Pen) would have greater softening of skin, lower frequency of renal crisis, and better survival than patients taking low-dose D-Pen. METHODS: Seventeen centers enrolled 134 SSc patients with early (< or =18 months) diffuse cutaneous scleroderma into a 2-year, double-blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus low-dose D-Pen (125 mg every other day). All 134 patients were followed up for a mean+/-SD of 4.0+/-1.1 years to assess the frequencies of new-onset scleroderma renal crisis (SRC) and mortality. RESULTS: Sixty-eight patients completed 24 months of drug treatment. The course of the modified Rodnan skin thickness score in the 32 high-dose and the 36 low-dose D-Pen completers was not different at 24 months: the skin score dropped 4.8+/-10.3 (mean+/-SD) units in the high-dose group and 6.9+/-8.4 units in the low-dose group (P = 0.384 by t-test; favoring low-dose D-Pen) from 20.4+/-10.3 in the high-dose and 19.9+/-6.6 in the low-dose D-Pen group at study entry. The incidences of SRC and mortality were not different (P > 0.38 by Cox proportional hazards and by chi-square test) in the 66 high-dose patients (8 developed SRC and 8 died) compared with the 68 low-dose patients (10 developed SRC and 12 died). Of the 20 adverse event-related withdrawals, 80% occurred in the high-dose D-Pen group. CONCLUSION: The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Adult↗

Correlates of the disability index of the health assessment questionnaire: a measure of functional impairment in systemic sclerosis.

OBJECTIVE: To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine). METHODS: The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of < 18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone > 10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. RESULTS: The mean (+/-SD) HAQ-DI score at entry was 1.04 +/- 0.67. Fifty-three percent of patients had HAQ-DI scores > or = 1.0 (signifying moderate-to-severe functional impairment). Multivariate logistic regression demonstrated that impaired fist closure > or = 23 mm (OR 4.24, 95% CI 1.68-10.70), reduced handspread < or = 175 mm (OR 4.5, 95% CI 1.80-11.24), joint tenderness count > or = 1.0 (OR 2.93, 95% CI 1.16-7.40), age > or = 43 years (OR 2.44, 95% CI 1.01-5.95), platelet count > or = 330,000/mm3 (OR 2.30, 95% CI 0.96-5.57), and female sex (OR 2.43, 95% CI 0.77-7.73) were the most important correlates of HAQ-DI scores > or = 1.0. CONCLUSION: Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced hand-spread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores > or = 1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory measures of SSc disease involvement. Abnormal HAQ-DI scores may support patient claims of functional impairment, help to focus physician attention on implementing measures to reduce functional impairment, and be useful in reflecting the disease course over time.

Adolescent↗

Cellular control over spicule formation in sea urchin embryos: A structural approach.

The spicules of the sea urchin embryo form in intracellular membrane-delineated compartments. Each spicule is composed of a single crystal of calcite and amorphous calcium carbonate. The latter transforms with time into calcite by overgrowth of the preexisting crystal. Relationships between the membrane surrounding the spiculogenic compartment and the spicule mineral phase were studied in the transmission electron microscope (TEM) using freeze-fracture. In all the replicas observed the spicules were tightly surrounded by the membrane. Furthermore, a variety of structures that are related to the material exchange process across the membrane were observed. The spiculogenic cells were separated from other cell types of the embryo, frozen, and freeze-dried on the TEM grids. The contents of electron-dense granules in the spiculogenic cells were shown by electron diffraction to be composed of amorphous calcium carbonate. These observations are consistent with the notion that the amorphous calcium carbonate-containing granules contain the precursor mineral phase for spicule formation and that the membrane surrounding the forming spicule is involved both in transport of material and in controlling spicule mineralization.

Animals↗