Initial experience of clinical pharmacology and clinical pharmacy interactions in a clinical pharmacokinetics consultation service

International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.     

Cytochemical studies of metaphase chromosomes by flow cytometry

The cytochemical properties of metaphase chromosomes from Chinese hamster and human cells were studied by flow cytometry. This technique allows precise quantitation of the fluorescence properties of individual stained chromosome types. Chromosomes were stained with the following fluorescent DNA stains: Hoechst 33258, DAPI, chromomycin A3, ethidium bromide, and propidium iodide. The relative fluorescence of individual chromosome types varied depending on the stain used, demonstrating that individual chromosome types differ in chemical properties. Flow measurements were performed as a function of stain and chromosome concentration to characterize the number and distribution of stain binding sites. Flow analysis of double stained chromosomes show that bound stains interact by energy transfer with little or no binding competition. For most hamster chromosomes, there is a strong correlation between relative fluorescence and stain base preference suggesting that staining differences may be determined primarily by differences in average base composition. A few hamster chromosome types exhibit anomalous staining which suggests that some other property, such as repetitive DNA sequences, also may be an important determinant of chromosomal staining.     

An evaluation of procedures used in staging carcinoma of the cervix

A review of 227 cases of invasive carcinoma of the cervix was undertaken to determine the efficacy of procedures using in the staging of this disease. All patients had a pretreatment chest radiography and intravenous pyelogram. 96.5% had pretreatment cystoscopy, 98.6% had pretreatment proctoscopy, and 92% had a pretreatment barium enema. These patients were retrospectively staged on the findings of physical examination only. Each additional procedure was then evaluated by comparison with the initial staging. Cystoscopy and chest film findings each would have changed the clinical stage in fewer than 1% of cases, barium enema in 1.4%, and proctoscopy in 2.2%. No patient had a positive barium enema without a positive proctoscopy, while two patients had positive proctoscopies with negative barium enemas. The overall yield of positive findings by pretreatment intravenous pyelography was 7.3%. Lymphangiography, although inconsistently done, yielded positive findings in all stages. Chest radiographs, intravenous pyelography, proctoscopy, and lymphangiography are recommended as part of the pretreatment workup of patients with carcinoma of the cervix. Routine barium enema is no longer recommended, and cystoscopy is only recommended in patients with clinical stage IIB disease or greater.     

GENOMIC HARDWIRING AND PHENOTYPIC PLASTICITY OF TERPENOID-BASED DEFENSES IN CONIFERS

Over evolutionary history, conifers have faced a myriad of threats from phloem- and xylem-feeding insects, defoliating insects, and fungal pathogens. Among the trees defenses, terpenoids appear to play a major role by harming, disabling, deterring, repelling, or otherwise reducing the fitness of potential invaders. Each of the three classes of terpenoids in conifers, monoterpenes, sesquiterpenes, and diterpenes, are composed of a large number of representative compounds. In most cases, the presence of a particular terpenoid compound in the oleoresin or volatile emissions from a specific conifer can be accounted for by the expression of one of many committed terpene synthase (TPS) genes. However, while each TPS may produce one or a few major products, many produce a variety of minor products with relatively constant component ratios in the product blends. TPS genes exist in conifers in large and functionally diverse, yet monophyletic, gene families. Within these gene families, new biochemical functions of TPS appear to have evolved by gene duplication and changes in the amino acid sequence of the enzymes active site. In addition, TPS genes may be differentially expressed prior to, during, and following attack by insects or pathogens. Thus, while the production of any particular terpenoid is hardwired into a conifers genome, these trees have the capacity to change the mixture of terpenoids in oleoresin secretions and volatile emissions. Anatomical changes may also accompany induced terpenoid production, supplementing the plasticity of the molecular and biochemical events.     

Pancreatic cancer screening. Analysis of the problem and the role of radionuclide imaging

The clinical, surgical, and pathologic findings in a five year prospective study of 192 patients referred with a high probability of pancreatic cancer are reported. We have defined the requirements of any pancreatic imaging procedure as its ability to distinguish a normal pancreas from pancreatic cancer or chronic pancreatitis and the capability of detecting tumors less than 5 cm in diameter. There was a 47 percent incidence of pancreatic disease (27 percent pancreatic cancer and 20 percent chronic pancreatitis). Prospective radionuclide imaging as routinely performed was found to be of little clinical value in this patient population; it was neither specific nor sensitive to pancreatic cancer or chronic pancreatitis. Preliminary data with longitudinal multiplane emission tomography show an improved diagnostic accuracy and the ability to detect resectable tumors, but its efficacy needs to be prospectively compared with other screening tests on a carefully defined patient population.     

The formation of different phases of CuxTe and their effects on CdTe/CdS solar cells

Material studies and device applications of Cu_xTe in an NREL-developed CdTe solar cell structured as glass/Cd₂SnO₄/ZnSnO_x/CdS/CdTe are presented. The Cu_xTe primary back contact was formed by evaporating a Cu layer with various thicknesses at room temperature on HNO₃/H₃PO₄ (NP) solution etched CdTe layer. A post-annealing was then followed. The structural evolution and electrical properties of Cu_xTe were investigated. Cu/Te ratio and post-annealing temperature are two processing parameters in this study. The Cu_xTe phases are mainly controlled by the Cu/Te ratio. After a post-annealing at a low temperature, such as 100 °C, no Cu_xTe phase transformation from its as-deposited phase was observed. A post-annealing treatment at a higher temperature, such as 250 °C, can reveal the stoichiometric Cu_xTe phases based on the Cu/Te ratio used in the devices. But a post-annealing at a further higher temperature, such as 400 °C, resulted in a complicated Cu_xTe phase appearance. CuTe, Cu_1.4Te, and Cu₂Te are three major phases detected by X-ray diffraction (XRD) for different Cu thickness application annealed at 250 °C. Application of Cu thicker than 60 nm degrades open-circuit voltage (V_oc) and shunting resistance (R_sh), but increases series resistance (R_s). The correlation between device performance and the Cu_xTe back contact illustrates that the process used for forming the Cu₂Te back contact failed to produce good fill factor (FF) and also introduced higher barrier height. The best device was observed for a back contact with a mixed Cu_1.4Te and CuTe phases.