Health-care providers' views of menopause and its management: a qualitative study.

OBJECTIVE: This study aimed to explore Australian health-care providers' knowledge of menopause and its consequences, and their views about menopause-related health care. METHODS: This was a cross-sectional qualitative study of Australian general practitioners (GPs), gynecologists (GYs) and pharmacists (PHs). Recruitment was ultimately achieved through professional networks and cold calling. RESULTS: There were equal numbers of GPs, GYs and PHs, and equal numbers of males and females in each group. All participants demonstrated sound understanding of menopause and its consequences. A strong theme was recognition of high usage of complementary and alternative medicines (CAMs) by women for menopausal symptoms. Most participants highlighted lack of efficacy evidence for most CAMs, but the majority of GPs and PHs considered CAMs to 'have a role'. Most supported menopausal hormone therapy (MHT) when symptoms impaired quality of life. Limitations to comprehensive care included knowledge gaps and lack of time. CONCLUSIONS: Australian health-care providers appeared knowledgeable about menopause, but uncertain about its management. MHT prescription appeared limited to women with severe symptoms despite lifestyle modification and a trial of CAMs. The upskilling of clinicians providing care for women at midlife, with respect to the indications for and prescribing of MHT, urgently needs to be addressed.

Comparing surface properties of melanoma cells using time of flight secondary ions mass spectrometry.

Various techniques have been already reported to differentiate between normal (non-malignant) and cancerous cells based on their physico-chemical properties. This is relatively simple when studied cancerous cells originate from distant stages of cancer progression. Here, studies on chemical properties of two closely related human melanoma cell lines are presented: WM115 melanoma cells were taken from the vertical growth phase while WM266-4 from the skin metastatic site of the same patient. Their chemical properties were studied by two techniques, namely time-of-flight secondary ion mass spectra (ToF SIMS) and photothermal microspectroscopy (PTMS), used to record mass and photothermal spectra of cells, respectively. In our approach, independently of the spectra type, its full range, i.e. masses and wavenumbers within the range 0-500 kDa and 500-4000 cm-1, underwent a similar methodology for principal component analysis (PCA). PCA outcome shows results groupped depending on the sample type (either WM115 or WM266-4 cells). The results are independent of the method applied to study chemical properties of melanoma cells, indicating that cancer-related changes are large enough to be identified with these techniques and to differentiate between cells originating from vertical growth phase and skin metastatis.

The development of microthermal analysis and photothermal microspectroscopy as novel approaches to drug-excipient compatibility studies.

The use of microthermal analysis as a novel means of assessing chemical incompatibility between drugs and excipients is assessed using magnesium stearate and acetylsalicylic acid as a model system. Localised thermomechanical analysis (L-TMA), localised differential thermal analysis (L-DTA), nanosampling, thermally assisted particle manipulation (TAPM) and photothermal microspectrometry (PTMS) are developed as a means of allowing extremely small quantities of drug and excipient to be heated in close proximity to each other. Differential scanning calorimetry (DSC), hot stage microscopy (HSM) and temperature controlled attenuated total internal reflection (ATR) FTIR were used as supportive techniques. L-TMA and macroscopic TMA of magnesium stearate indicated that the endothermic DSC peak normally associated with melting does not correspond to significant liquefaction. An optimised method for detecting the interaction at a particulate level of scrutiny was developed whereby the drug is placed on the excipient surface via TAPM and the construct heated, allowing the interaction to be detected in both the L-TMA and L-DTA signal. PTMS allowed spectra to be obtained on nanogram-sized samples and also allowed the interaction to be detected. The study has therefore demonstrated the potential for using TAPM with PTMS for studying interactions at an individual particle level.

Macrophages, lymphocytes and major histocompatibility complex (HLA) class II antigens in adult human sensory and sympathetic ganglia.

We report an immunocytochemical study of sensory and autonomic ganglia from ten adult human subjects aged 18-83 years without peripheral nerve disease using monoclonal antibodies to macrophages, lymphocytes and human leukocyte (HLA) class II antigens. All ganglia and their associated nerve roots were found to contain a population of resident macrophages which accounted for 5-20% of the cells present. These macrophages and, in addition, many Schwann cells and satellite cells, gave reactions for HLA class II antigens in all cases. Very low numbers of CD3 and CD8 lymphocytes were also regularly detectable in sensory and autonomic ganglia. The resident macrophages may have important immunological and trophic functions. Their possible role in the development of immune-mediated peripheral nerve disease deserves further study.

The inhibition of bovine herpesvirus-1 by methyl 2-pyridyl ketone thiosemicarbazone and its effects on bovine cells.

Methyl 2-pyridyl ketone thiosemicarbazone (MPKT) was found to inhibit bovine herpesvirus-1 (BHV-1) at an ED50 concentration of approximately 5-10 microM. Several virus strains were shown to have similar sensitivity to the drug and serial passage of virus in the presence of MPKT failed to yield resistant progeny. There was evidence for toxic effects on cells at drug concentrations similar to those required to inhibit virus and passage of cells in low concentrations of MPKT gave results suggesting cumulative toxicity. Pre-incubation of cells in the presence of MPKT produced a residual antiviral effect. Taken together, these observations cast doubt on the selectivity of the drug for BHV-1, at least in the bovine system under test.

Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain.

Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection.

The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study.

To elucidate the cellular mechanisms of tissue injury in paraneoplastic states, tissues from two patients with small cell carcinoma of the lung and paraneoplastic neurological syndromes were studied. One patient had encephalitis with ganglionitis, and the other ganglionitis. Immunocytochemistry on brain and ganglia was performed using monoclonal and polyclonal antibodies. The majority of the inflammatory cells in brain and ganglia were T-cells, of both helper and cytotoxic subtypes. There were more macrophages in the inflammatory infiltrate of ganglia than in the brain of encephalitis. Major histocompatibility complex class I and II antigen expression was greater in the mononuclear cells in brain than in ganglia. There was no evidence of complement deposition and little evidence for antibody synthesizing cells. Our findings suggest a T-cell-mediated immune attack in paraneoplastic ganglionitis and encephalitis, with a greater role for macrophages in ganglionitis.

Two new microscopical variants of thermomechanical modulation: scanning thermal expansion microscopy and dynamic localized thermomechanical analysis

We describe two ways in which thermomechanical modulation may be used in conjunction with scanning thermal microscopy, in order to distinguish between different components of an inhomogeneous sample. The sample is subjected to a modulated mechanical stress, and the heating is supplied locally by the probe itself. Scanning thermal expansion microscopy is an imaging mode, in which an imposed localized temperature modulation is used to generate thermal expansion, which in turn produces mechanical strain and gives thermal expansion contrast images. We present results using two types of active thermal probe. For polymer/resin samples, the depth of material contributing to the measured thermal expansion is typically a few micrometres. Under certain conditions we observe a reversal in contrast as the frequency of the temperature modulation is increased. In dynamic localized thermomechanical analysis, the modulated stress is applied directly, and accompanied by a localized temperature change, as used in other forms of localized thermal analysis. The resulting modulated lateral force signals are obtained. The glass transition of polystyrene is detected, and shows a significant variation with frequency. The amplitude or phase signal may be used to obtain image contrast for inhomogeneous samples.

Micro-thermal analysis: scanning thermal microscopy and localised thermal analysis.

Micro-thermal analysis combines the imaging capabilities of atomic force microscopy with the ability to characterise, with high spatial resolution, the thermal behaviour of materials. The conventional AFM tip is replaced by a miniature heater/thermometer which enables a surface to be visualised according to its response to the input of heat (in addition to measuring its topography). Areas of interest may then be selected and localised thermal analysis (modulated temperature calorimetry and thermomechanical analysis) carried out. Localised dynamic mechanical measurements are also possible. Spatially resolved chemical analysis can be performed using the same basic apparatus by means of pyrolysis gas chromatography-mass spectrometry or high-resolution photothermal infrared spectrometry.

An investigation into the use of micro-thermal analysis for the solid state characterisation of an HPMC tablet formulation.

The use of micro-thermal analysis (microTA) as a novel means of differentiating between components in a model tablet formulation is described. This technique involves a modification of atomic force microscopy (AFM) such that the standard AFM tip is replaced with a Wollaston wire, thereby allowing the probe to act as a thermistor and temperature probe. Consequently it is possible to map not only the topology but also the thermal conductivity of the sample. Furthermore, it is possible to apply a heating signal to the material and thereby to perform thermal analysis on highly localised regions of the sample. Compacts were prepared comprising ibuprofen, HPMC E4M prem and 1:1 mixes of the two components and analysed using a microTA micro-thermal analyser. The surface topology and conductivity images of the three systems are reported. In addition, the ability of the technique to perform thermal analysis on highly specific regions of the sample is described. The method was able to differentiate between the components of the sample on the basis of micro-thermomechanical experiments. The implications of the use of the technique for the study of pharmaceutical tablets is discussed.

Detection of high levels of canine herpes virus-1 neutralising antibody in kennel dogs using a novel serum neutralisation test.

It is widely held that only cells of canine origin support canine herpesvirus-1 (CHV-1) replication and, that cytopathic effect (CPE) develops relatively slowly. Here we show that mink fetal lung cells (NBL-7 cell line) are permissive for CHV-1 and can be used to produce a sensitive test for neutralising antibody by plaque reduction in the presence of complement. The test was applied to the investigation of CHV-1 virus neutralising antibody levels in three kennel populations. The results showed that 26 out of 28 dogs were neutralising antibody positive (titre >/=2), and, 11 out of 28 had titres of >/=1024. The serum samples were analysed by enzyme linked immunoassay (ELISA); 27 out of 28 were graded as ELISA IgG positive (titre >/=500) and 26 of 28 were graded as ELISA IgM positive (titre >/=50).