Feasibility of Telemonitoring Blood Pressure in Patients With Kidney Disease (Oxford Heart and Renal Protection Study-1): Observational Study.

BACKGROUND: Blood pressure (BP) is a key modifiable risk factor for patients with CKD, with current guidelines recommending strict control to reduce the risk of both progression of CKD and cardiovascular disease. Trials of BP lowering require multiple visits to achieve target BP which increases the costs of such trials, and in routine care BP measured in clinic may not accurately reflect usual BP. OBJECTIVE: We sought to assess whether a telemonitoring system for BP (using a Bluetooth-enable BP machine which could transmit BP measurements to a tablet device which had a bespoke app to guide measurement of BP and collect questionnaire data) was acceptable to patients with CKD, and whether patients would provide sufficient BP readings to assess variability and guide treatment. METHODS: 25 participants with CKD were trained to use the telemonitoring equipment, asked to record BP daily for 30 days, attend a study visit, and then record BP on alternate days for the next 60 days. They were also offered a wrist-worn applanation tonometry device (BPro) which measures BP every 15 minutes over a 24 hour period.Participants were given questionnaires at the one-month and three-month time points, derived from the System Usability Scale and Technology Acceptance Model. All eligible participants completed the study. RESULTS: Mean age was 58 (SD 11) years and mean eGFR was 36 (SD 13) mL/min/1.73m2. 13 out of 25 (52%) participants provided >90% of expected data and 18 out of 25 (72%) provided >80% expected data. The usability of the telemonitoring system was rated highly with mean scores of 84.9/100 (SE 2.8) after 30 days and 84.2/100 (SE 4.1) after 90 days. The coefficient of variation (CV) for variability of telemonitoring systolic BP was 9.4% (95% confidence interval [CI] 7.8 to 10.9), compared to 7.9% (95% CI 6.4-9.5) for the BPro device (P=0.05) (and 9.0% over one year in a recently completed trial with identical eligibility criteria), indicating that most variation in BP is short-term. CONCLUSIONS: Telemonitoring is acceptable to patients with CKD and provides sufficient data to inform titration of antihypertensive therapies in either a randomized trial setting (comparing different targets BPs) or routine clinical practice. Such methods could be employed in both scenarios and reduce costs currently associated with such activities.Registration ISRCTN13725286.

Using the simplified case mix tool (sCMT) to identify cost in special care dental services to support commissioning.

To commission dental services for vulnerable (special care) patient groups effectively, consistently and fairly an evidence base is needed of the costs involved. The simplified Case Mixed Tool (sCMT) can assess treatment mode complexity for these patient groups. OBJECTIVE: To determine if the sCMT can be used to identify costs of service provision. CLINICAL SETTING: Patients (n=495) attending the Sussex Community NHS Trust Special Care Dental Service for care were assessed using the sCMT. MAIN MEASURES: sCMT score and costs (staffing, laboratory fees, etc.) besides patient age, whether a new patient and use of general anaesthetic/intravenous sedation. METHOD: Statistical analysis (adjusted linear regression modelling) compared sCMT score and costs then sensitivity analyses of the costings to age, being a new patient and sedation use were undertaken. Regression tables were produced to present estimates of service costs. RESULTS: Costs increased with sCMT total scale and single item values in a predictable manner in all analyses except for 'cooperation'. Costs increased with the use of IV sedation; with each rising level of the sCMT, and with complexity in every sCMT category, except cooperation. CONCLUSION: Costs increased with increase in complexity of treatment mode as measured by sCMT scores. Measures such as the sCMT can provide predictions of the resource allocations required when commissioning special care dental services.

Mass spectrometric detection and measurement of N2-(2'-deoxyguanosin-8-yl)PhIP adducts in DNA.

Capillary column gas chromatography-electron-capture mass spectrometry (GC-MS) and microbore liquid chromatography-positive ion electrospray mass spectrometry (LC-MS) have been used to measure the carcinogenic, food-derived, heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) adducted at C-8 of deoxyguanosine in DNA. For GC-MS analysis, PhIP was released from adducted DNA by alkaline hydrolysis and analysed as the di(3,5-bistrifluoromethylbenzyl) derivative, while for LC-MS analysis, the nucleoside N2-(2'-deoxyguanosin-8-yl)PhIP was generated by enzymic digestion of DNA and analysed intact. A deuterated analogue of N2-(2'-deoxyguanosin-8-yl)PhIP was used as an internal standard in both assays, which each had a limit of quantification of 200 pg/500 microg DNA. The two methods were used to analyse DNA extracted from h1A2v2 cells and HCT116 cells that had been exposed to PhIP.

Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers.

1. The in vitro metabolism of n-hexane was studied in rat liver, lung, brain and skeletal muscle microsomes and in microsomes prepared from cell lines expressing human cytochrome P-450 2E1 or 2B6. The hydroxylated metabolites of n-hexane were quantified by gas chromatography-mass spectometry. 2. Rat liver and extensor digitorum longus (EDL, fast-twitch skeletal muscle) microsomes and the CYP 2B6 microsomes produced the pre-neurotoxic metabolite of n-hexane, 2-hexanol as a major metabolite in contrast to the other rat tissues examined. 3. Inhibition of 2- and 3-hexanol production from n-hexane by rat lung microsomes using metyrapone, an inhibitor of cytochrome P-450 2B1 activity, resulted in almost complete inhibition of lung microsomal activity. 4. Production of all three hexanols was significantly increased with phenobarbital-induced rat liver microsomes, with a 10-fold increase in 2- and 3-hexanol production. A slight increase in 2-hexanol production with phenobarbital-induced rat EDL and brain microsomes was observed. No increase in n-hexane metabolism was noted following induction with beta-naphthoflavone or with ethanol.

An investigation into the role of rat skeletal muscle as a site for xenobiotic metabolism using microsomes and isolated cells.

1. The role of skeletal muscle microsomes as a site of extrahepatic xenobiotic metabolism using n-hexane as a model substrate was investigated. The observed cytochrome P450-dependent metabolism was compared with that found with liver, and brain microsomal fractions. 2. Rat skeletal muscle microsomes metabolised n-hexane to 1-, 2- and 3-hexanol at rates 40-300 times lower than observed with rat liver microsomes. 3. Fast-twitch extensor digitorum longus muscle (EDL) microsomes had twice as much n-hexane hydroxylase activity as the slow-twitch soleus and furthermore the EDL microsomes produced 2-hexanol, a bioactivation product of n-hexane, as a major metabolite. 4. Metabolism of hexane to 1-, 2- and 3-hexanol and 2-hexanon was demonstrated in cultured rat myoblasts. 5. Ethoxyresorufin and pentoxyresorufin O-dealkylation were not detected in either muscle microsomes or myoblasts although immunocytochemical localisation studies were suggestive of the presence of cytochrome P-450. 6. In conclusion, rat skeletal muscle has a low level of xenobiotic metabolism activity. The relevance to neuromuscular toxicity of n-hexane is discussed.

Heterocyclic amines: evaluation of their role in diet associated human cancer.

1. Heterocyclic amines are formed in parts per billion levels when meat is cooked. 2. The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food. 3. We have shown that MeIQx and PhIP, both in vitro and in vivo, are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines. 4. MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt, we have shown that PhIP induces a characteristic mutational 'fingerprint'. 5. MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.

Temporal changes in LH and testosterone and their relationship with the first antler in red deer (Cervus elaphus) stags from 3 to 15 months of age.

Blood samples were taken from six tame red deer stags at 3-15 months of age once a month from a jugular catheter every 30 min for 24 h to investigate hormonal secretion during puberty and during growth of the pedicle and first antler. All plasma samples were analysed for LH and testosterone concentrations and the resultant data were analysed using the PULSAR pulse detection routine. In addition each stag was injected wih gonadotrophin-releasing hormone (GnRH; 20 ng/kg body weight) after the above samples had been taken and the bleeding regimen was continued for a further 2 h. Body weight, antler size and status (i.e. whether the stags had a pedicle or antler) were also recorded. The pulsatile secretion of LH could be considered to have occurred in three phases. The first of these was one of development, with the LH pulse frequency increasing to 8 pulses/24 h, the second a phase of regression, with a decrease in LH pulse frequency to 2 pulses/24 h, and finally a second phase of development characterized by increased LH pulse frequency to 12 pulses/24 h. Testosterone secretion generally followed the same pattern. During the period before the permanent bony pedicles grew, there were less than five LH pulses/24 h. When the pedicles were growing, LH and testosterone pulsatile secretion increased but the pulse frequency of both hormones fell during velvet antler growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile growth hormone, insulin-like growth factors and antler development in red deer (Cervus elaphus scoticus) stags.

Plasma samples taken every 30 min over a 26-h period each month from six 4- to 15-month-old red deer stags were analysed for GH. In addition, two samples taken at 10.00 and 22.00 h were analysed for insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II). A concentrate diet was available ad libitum. Food intake, body weight and antler status were recorded. Concentrations of GH were analysed using the PULSAR peak detection routine. Secretion of GH was pulsatile in every month of sampling, but the pattern of pulsatility differed seasonally. During the autumn and early winter (April-June in the Southern hemisphere) GH pulses were frequent and of low amplitude. In contrast, GH pulses in spring (August-September) were of high amplitude and high frequency resulting in a high mean level of GH circulating in the plasma. In early summer (November) the GH pulse amplitude was much lower and pulse frequency fell. There was a rise in GH pulse frequency not accompanied by an increase in GH pulse amplitude in summer (December-January). GH pulse amplitude seemed to be the main determinant of mean GH plasma level. Secretion of IGF-I was raised 1 month after peak monthly mean GH secretion. There was little consistent relationship between concentrations of IGF-II and mean daily GH. Concentrations of GH correlated positively and significantly with liveweight gain and antler growth rate with a delay of 1 month. Significantly positive correlations between concentrations of IGF-I, liveweight gain and antler growth rate were observed. It is considered that the spring and summer (September-December) seasonal acceleration of liveweight gain and antler development in stags could be a consequence of high winter/early spring (August-September) GH pulse frequency and amplitude resulting in increased concentrations of IGF-I, particularly in October.

Plasma LH and testosterone responses to gonadotrophin-releasing hormone in adult red deer (Cervus elaphus) stags during the annual antler cycle.

Eight adult red deer stags were given an i.v. injection of synthetic gonadotrophin-releasing hormone (GnRH) on seven occasions at various stages of the antler cycle, namely hard antler in late winter, casting, mid-velvet growth, full velvet growth, antler cleaning and hard antler both during the rut and in mid-winter. The stags were allocated at random on each occasion to one of four doses, i.e. 1, 3, 10 or 95 micrograms GnRH. Blood samples were taken before GnRH injection and for up to 2 h after injection. Pituitary and testicular responses were recorded in terms of plasma LH and testosterone concentrations. There was an increase in plasma concentration of LH after the GnRH injection in all stags at all stages of the antler cycle. Dose-dependent responses of LH to GnRH in terms of area under the curve were apparent at all stages of the antler cycle. The lowest responses were recorded at casting, during velvet antler growth and at the rut sampling. The pattern of testosterone response reflected the inter-relationship of the antler and sexual cycles with very low testosterone responses occurring at casting and during velvet antler growth. The responses were higher at antler cleaning and then increased to a maximum at the rut before declining to reach their nadir at casting. The results are consistent with a hypothesis that the antler cycle, as a male secondary sexual characteristic, is closely linked to the sexual cycle and its timing is controlled by reproductive hormones. Low plasma concentrations of testosterone, even after LH stimulation, are consistent with the hypothesis that testosterone is unnecessary as an antler growth stimulant during growth.

The effect of gastro-intestinal parasitism on the temporary dentition of lambs.

The temporary dentitions of 18 to 39-week-old lambs with a very light or a very heavy parasite burden are compared. The heavily parasitised lambs developed longer temporary incisors which tended to protrude further forward in relation to the upper dental pad. They showed absolute hypocalcaemia and hypoalbuminaemia and relative hypophosphataemia and hypoproteinaemia and in the alveolar bone of the mandible there was a reduction in ash and matrix densities and matrix mineralisation. The incisor protrusion and lengthening may have been a consequence of the loss of supporting bone, but inappetance was likely to have been a factor contributing to the lengthening.