A High Energy X-ray Diffraction Study of Amorphous Indomethacin.

Amorphous pharmaceuticals often possess a wide range of molecular conformations and bonding arrangements. The x-ray pair distribution function (PDF) method is a powerful technique for the characterization of variations in both intra-molecular and inter-molecular packing arrangements. Here, the x-ray PDF of amorphous Indomethacin is shown to be particularly sensitive to the preferred orientations of the chlorobenzyl ring found in isomers in the crystalline state. In some cases, the chlorobenzyl ring has no preferred torsional angle in the amorphous form, while in others evidence of distinct isomer orientations are observed. Amorphous samples with no preferred torsion angles of the chlorobenzyl ring are found to favor enhanced inter-molecular hydrogen bonding, and this is reflected in the intensity of the first sharp diffraction peak. These significant variations in structure rule out amorphous Indomethacin as a possible standard for x-ray PDF measurements. At high humidity, time resolved PDF's for >40 h reveal water molecules forming hydrogen bonds with Indomethacin molecules. A simple linear hydrogen bond model indicates that water molecules in the wet amorphous form have similar hydrogen bond strengths to those found between Indomethacin dimers or chains in the dry amorphous form.

Distribution effects on 1H double-quantum MAS NMR spectra.

The effect of a distribution in the (1)H-(1)H dipolar coupling on (1)H double-quantum (DQ) magic angle spinning (MAS) nuclear magnetic resonance (NMR) spinning sideband patterns is considered. In disordered or amorphous materials a distribution in the magnitude of the (1)H-(1)H dipolar coupling is a realistic possibility. Simulations of the (1)H DQ MAS NMR spinning sideband spectra were performed with the two-spin approximation. These simulations reveal that a dipolar coupling distribution can greatly affect the DQ spectral shape and behavior of the DQ build-up. The spectral line shapes are quantified by measurement of the relative intensities of the DQ sidebands. These variations in the (1)H DQ NMR spectra are evaluated as a function of the width of the dipolar coupling distribution. As an example, the experimental DQ spinning sideband spectrum for a hydrated polyoxoniobate containing 15 H(2)O molecules per hexaniobate cluster, are better simulated with a distribution of dipolar couplings opposed to a single coupling constant.

Risk factors for lyme disease in Chester County, Pennsylvania.

OBJECTIVE: To identify factors associated with increased or decreased risk of infection for Lyme disease in Chester County, Pennyslvania. METHODS: The authors designed an unmatched case-control study involving 294 incident cases reported to the Chester County Health Department in 1998 and 449 controls selected by random digit dialing. All case and control participants were interviewed by telephone. RESULTS: Age is a risk factor for Lyme disease for groups aged 10-19 years old and 50 years or older. Sex was not a risk factor. Incidence of Lyme disease in a rural setting was three times the incidence in an urban setting. Increased risk also was associated with living in single family homes, homes with yards or attached land, woods on the land, signs of tick hosts seen on the land, and homes within 100 feet of woodland. Gardening for more than four hours per week was also a risk factor, but most other outdoor activities were not. Twice as many participants took protective measures against tick bites before outdoor employment than those who merely ventured into the yard or land associated with the home. Only checking for ticks during outdoor activity and the use of repellents prior to outdoor activities outside the yard were unequivocally associated with a reduced risk of Lyme disease. CONCLUSIONS: It is important to increase public awareness about the risk of acquiring Lyme disease from ticks in the immediate environment of the home.

Evaluation of bovine viral diarrhea virus control using a mathematical model of infection dynamics.

A mathematical model for infection with bovine viral diarrhea virus (BVDV) was created comprising a series of coupled differential equations. The model architecture is a development of the traditional model framework using susceptible, infectious and removed animals (the SIR model). The model predicts 1.2% persistent infection (within the range of field estimates) and is fairly insensitive to alterations of structure or parameter values. This model allows us to draw important conclusions regarding the control of BVD, particularly with respect to the importance of persistently infected (PI) animals in maintaining BVD as an endemic entity in the herd. Herds without PI animals are likely to experience episodic reproductive losses at intervals of two to three years, unlike herds with PI animals which will not see such marked episodic manifestations of infection. Instead, these herds will experience an initial peak of disease which will settle to low-level chronic reproductive losses. The model indicates that vaccine coverage for herd immunity (to avoid episodic manifestations of disease) need be only 57% without PI animals, although 97% coverage is required when PI animals are present. Analysis of model behavior suggests a program of detection and removal of PI animals may enhance the effectiveness of a vaccine program provided these animals are in the herd for 10 days or less. The best results would be seen with PI animals in the herd for 5 or fewer days.