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J N Harvey

Publications and source records attributed to J N Harvey.

At least 19 recordsLinked to original sources

Diabetic nephropathy.

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Diabetes Mellitus, Type 1↗

Estimation of the prevalence of diagnosed diabetes from primary care and secondary care source data: comparison of record linkage with capture-recapture analysis.

STUDY OBJECTIVE: To compare multiple source linkage and capture-recapture analysis in determining the current age and gender specific prevalence of type 1 and type 2 diabetes in a UK white population. To assess whole population trends in diabetes prevalence and treatment by comparison with previous studies. DESIGN: Data were obtained from hospital sources and all 74 general practices in the study population. Analyses were carried out both by record linkage and by use of a two source capture-recapture model to correct for incomplete ascertainment. SETTING: County of Clwyd, North Wales: total population 418,200. MAIN RESULTS: By record linkage the age adjusted prevalence of all diabetes was 2.04 (95% confidence intervals 2.00 to 2.09)%. Using the capture-recapture method it was 2.29 (2.24 to 2.33)%. From capture-recapture data the age adjusted prevalence of type 1 diabetes was 0.40 (0.37 to 0.43)% in men and 0.28 (0.25 to 0.30)% in women; the prevalence of type 2 was 2.03 (1.97 to 2.09)% in men and 1.67 (1.62 to 1.72)% in women. These figures represent an increase compared with previous surveys. The age specific prevalence of type 2 diabetes was greater in men in a ratio of approximately 1.5:1 and there were more patients treated by diet alone. CONCLUSIONS: Record linkage using multiple sources underestimates the prevalence of diabetes compared with capture-recapture estimates. The results suggest the prevalence of known diabetes in the UK has approximately doubled in less than 20 years. There is an increasing preponderance of male patients and of patients treated currently with diet alone.

Adolescent↗

A computational study of ethylene C-H bond activation by.

It has previously been demonstrated that both [(C5Me5)Ir(PMe3)(CH=CH2)H] and [(C5Me5)Ir(PMe3)(H2C=CH2)] are formed when [(C5Me5)Ir(PMe3)] is thermolytically generated in the presence of ethylene. At higher temperatures, the vinyl hydride is converted to the eta2-ethylene adduct. Density functional theory has now been used to investigate this reaction, using the B3LYP functional, two types of basis sets (LanL2DZ and TZV*), and two models of the [(C5R5)Ir(PR3)] species (R=H and CH3). The study consists of full optimizations of local minima, first-order saddle points, and minimum energy crossing points (MECP). The experimental results are best accounted for by considering both singlet and triplet spin surfaces. The relative energies of singlet [(C5R5)Ir(PR3)(CH3)H], [(C5R5)Ir(PR3)(CH=CH2)H], and [(C5R5)Ir(PR3)(H2C=CH2)] are in good agreement with experiment, as is the calculated barrier for the conversion from the vinyl hydride to the eta2-alkene complex. However, the singlet surface alone fails to explain the experimentally observed product ratio, or the intermediate inferred from experimental isotope effect studies. Locating the MECP between singlet and triplet surfaces indicates that the thermolysis of the singlet alkyl hydride precursor directly forms triplet [(C5R5)Ir(PR3)]. The weak vanderWaals adduct of triplet [(C5R5)Ir(PR3)] and ethylene is proposed to be the key intermediate in the overall reaction. The interchanging of the available ethylene C-H bonds in this triplet sigma complex accounts for the observed kinetic isotope effects, and partitioning between alkene pi-complexation and C-H bond activation may also occur from this common intermediate. The possible role of steric factors and molecular dynamics are also discussed.

Journal Article↗

Platinum dioxide cation: easy to generate experimentally but difficult to describe theoretically.

A formal platinum(V) dioxide cation [Pt,O2](+) can be generated in the gas phase by successive oxidation of Pt(+) with N2O. The ion's reactivity is in keeping with the dioxide structure OPtO(+), rather than with [Pt,O2](+) isomers having intact O-O bonds, e.g., the dioxygen complex Pt(O2)(+) and peroxo species PtOO(+). Inter alia due to the high ionization energy of the neutral counterpart (11.2 eV), the [Pt,O2](+) cation is a rather aggressive reagent toward oxidizable neutrals. [Pt,O2](+) is even capable of activating inert substrates such as H2, CO, and CH4. Further, a sequence for the catalytic conversion CO + N(2)O --> CO2 + N2 is described with a turnover number of >100 for the catalytically active species PtOn(+) (n = 0-2). As a consequence of the high reactivity, however, the observed selectivities with most substrates are rather poor. For example, the reaction of PtO2(+) with ethane gives rise to 10 different product channels. In an attempt to analyze the structural features and different minima of the [Pt,O2](+) system, extensive ab initio studies are performed. While correlated ab initio methods describe the system reasonably well, density functional theory turns out to be much less accurate in terms of both structural and energetic descriptions.

Journal Article↗

Population-based survey and analysis of trends in the prevalence of diabetic nephropathy in Type 1 diabetes.

AIMS: To determine the prevalence of the various stages of diabetic nephropathy in Type 1 diabetes in a population-based survey. To make direct comparison with results from previous published studies to assess current trends. METHODS: Identification of all Type 1 patients using a population-based diabetes register. Urine samples for albumin assay were obtained at clinic visit and by postal request. Prevalence rates were calculated specifically for direct comparisons with previously published surveys. RESULTS: This study and European data from the 1990s show a clear reduction in the cumulative prevalence of microalbuminuria and established nephropathy compared with surveys from Copenhagen (1985), Pittsburgh (1986-8) and Boston (1992). In North Wales in 1999 the overall cumulative prevalence of microalbuminuria was 27.2% (95% confidence interval (CI) 24.3-30.1%) and established nephropathy was 9.6% (7.7-11.5%). Comparisons with data from EURODIAB and from Spain indicated similar results, although the prevalence of microalbuminuria was lower in North Wales than in the EURODIAB study. Significantly lower rates of nephropathy were seen in more recent Swedish cohorts. Diabetic nephropathy remains more common in males. Microalbuminuria before 10 years duration of diabetes was seen at all post-pubertal ages. CONCLUSIONS: Rates of nephropathy in Europe in the 1990s are lower than a decade ago. Modern methods of management are therefore associated with demonstrable benefit at the population level. The lowest rates of nephropathy are associated with optimum glycaemic control in Swedish data, indicating the importance of metabolic in addition to haemodynamic factors.

Albuminuria↗

The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy.

The changes in renal kallikrein synthesis through normal pregnancy and its relation to aldosterone excretion and the glomerular filtration rate was investigated. Overnight urinary kallikrein and aldosterone excretion rates and glomerular filtration rate were measured at 18 weeks, 34 weeks, term and postpartum in normal human pregnancy. Kallikrein excretion was raised at 18 weeks compared with the nonpregnant state (P < 0 x 001) but was significantly reduced at term. The reduction in renal kallikrein was not due to falling aldosterone concentration, which increased in the third trimester, compared with 18 weeks (P = 0 x 002) and remained elevated at term compared with the nonpregnant state (P < 0 x 001). Glomerular filtration rate remained elevated at term despite the reduced kallikrein excretion rate. These data are consistent with the hypothesis that increased aldosterone production is one factor responsible for increased kallikrein synthesis which contributes to elevated glomerular filtration rate in early pregnancy. Other factors clearly inhibit renal kallikrein production at term. In the face of plasma volume expansion associated with increased mineralo-corticoid production, the effects of reduced kallikrein synthesis at term on glomerular perfusion and reabsorption of sodium by the distal tubule may predispose to blood pressure elevation in late pregnancy.

Aldosterone↗

A systematic review of drug induced ocular reactions in diabetes.

AIMS: To conduct a systematic review of drug induced adverse ocular effects in diabetes to determine if this approach identified any previously unrecognised adverse drug effects; to make a preliminary assessment of the feasibility of this approach in identifying adverse drug reactions; and to assess the current accessibility of this information to prescribing physicians. METHODS: Literature search of online biomedical databases. The search strategy linked eye disorders with adverse drug reactions and diabetes. Source journals were classified as medical, pharmaceutical, diabetes related, or ophthalmological. It was determined whether the reactions identified were recorded in drug datasheets and the British National Formulary. RESULTS: 63 references fulfilled the selection criteria, of which 45 were considered to be relevant to the study. The majority of these were case reports but cross sectional surveys, case-control and cohort studies, and review articles were also identified. 61% of the reactions were not recorded in the British National Formulary and 41% were not recorded in the datasheets. 55% appeared in specialist ophthalmology journals. CONCLUSIONS: This is a feasible approach to the identification of adverse drug reactions. Adverse reactions not listed in the most commonly used reference sources were found. The majority were published in specialist ophthalmology journals which might not be seen by prescribing physicians.

Chlorpropamide↗

Hyperthyroidism and radio-iodine therapy in a district general hospital.

A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.

Adult↗

Renal excretion of kallikrein and eicosanoids in patients with type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function.

Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption (derived from lithium clearance) and renal excretion rates of kallikrein, prostaglandin E2 and systemic and renally-derived metabolites of prostacyclin and thromboxane A2 were measured in patients with Type 1 (insulin-dependent) diabetes mellitus and in normal subjects. Diabetic patients with glomerular hyperfiltration had greater active kallikrein and prostaglandin E2 excretion than patients with normal glomerular filtration rate or than normal control subjects. Both active kallikrein and prostaglandin E2 excretion correlated directly with glomerular filtration rate. Active kallikrein excretion correlated directly with the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto prostaglandin F1 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, thromboxane B2, 2,3 dinor thromboxane B2 and 11-dehydro thromboxane B2 excretion were not different between the groups. This study confirms in man our previous finding of increased renal kallikrein production in the hyperfiltering streptozotocin-diabetic rat model. Given that kinins generated by kallikrein are extremely potent vasodilators and stimulate the renal production of eicosanoids that also regulate glomerular function, our findings suggest that increased kallikrein activity and prostaglandin E2 production may contribute to renal vasodilatation and hyperfiltration in human diabetes. The localization of kallikrein in the distal connecting tubule makes it plausible that altered sodium transport in the distal tubule may be a signal to increase generation of kallikrein.

Adult↗

Endocrine dysfunction in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found.

Child↗

Oncogenous osteomalacia and malignancy.

An example of oncogenous osteomalacia is described in association with the rate mesenchymal chondroblastoma. The tumour was characterized with a variety of immunohistochemical antibodies which confirmed its mesenchymal origin. Despite several surgical excisions of local recurrence, plasma 1,25-dihydroxyvitamin D3 concentrations (off treatment) indicate continued tumour activity and the continuing need for vitamin D therapy. This case and two others briefly discussed illustrate some of the difficulties in diagnosis and in achieving a cure in cases of oncogenous osteomalacia. Oncogenous osteomalacia in association with any malignant tumour is rare, there being eight previously recorded cases. Details of these cases are briefly reviewed for comparison. Despite undoubted malignancy our patient has survived 30 years from presentation indicating the benefits of aggressive surgical management.

Adult↗

Glomerular and tubular proteinuria in type 1 (insulin-dependent) diabetic patients with and without retinopathy.

We compared the urinary excretion of albumin, transferrin, N-acetyl-beta-D-glucosaminidase and alpha-1-microglobulin in 78 Type 1 (insulin-dependent) diabetic patients: 39 with retinopathy and 39 without. The two groups were matched for age, sex and duration of diabetes. The patients with retinopathy had increased excretion (median and range) of albumin [1.7(0.3-399.1) versus 1.0(0.3-116.6) mg/mmol creatinine, P less than 0.05], transferrin [114.2 (4.1-37126.2) versus 33.4 (1.0-4176.7) micrograms/mmol creatinine, P less than 0.01] and N-acetyl-beta-D-glucosaminidase [23.8 (1.1-119.1) versus 15.0 (0.1-65.1) mumol/h/mmol creatinine, P less than 0.05] but not alpha-1-microglobulin. Transferrin excretion correlated with albumin excretion. The prevalence of increased transferrin excretion (transferrinuria) was greater than that of microalbuminuria in patients both with and without retinopathy (P less than 0.01 in both cases). Urinary transferrin seems likely to be predominantly of glomerular origin and merits prospective longitudinal evaluation as a potential index of the microangiopathic process.

Acetylglucosaminidase↗

Renal hyperfiltration states: relationship to kallikrein and kinins.

Animal models and humans with glomerular hyperfiltration and hyperperfusion secondary to diabetes or high protein diet show increased renal production of kallikrein and kinins. Acute aminoacid infusion or ingestion also raises GFR, RPF and urinary kinins. Treatment with aprotinin or a kinin receptor antagonist reverses or prevents hyperfiltration in these rat models.

Animals↗