PubMed Health⌕ Search

Biomedical subjects

T Cundy

Publications and source records attributed to T Cundy.

At least 19 recordsLinked to original sources
PubMed2005

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment.

Camurati-Engelmann disease (CED) is a rare autosomal dominant type of bone dysplasia. This review is based on the unpublished and detailed clinical, radiological, and molecular findings in 14 CED families, comprising 41 patients, combined with data from 10 other previously reported CED families. For all 100 cases, molecular evidence for CED was available, as a mutation was detected in TGFB1, the gene encoding transforming growth factor (TGF) beta1. Pain in the extremities was the most common clinical symptom, present in 68% of the patients. A waddling gait (48%), easy fatigability (44%), and muscle weakness (39%) were other important features. Radiological symptoms were not fully penetrant, with 94% of the patients showing the typical long bone involvement. A large percentage of the patients also showed involvement of the skull (54%) and pelvis (63%). The review provides an overview of possible treatments, diagnostic guidelines, and considerations for prenatal testing. The detailed description of such a large set of CED patients will be of value in establishing the correct diagnosis, genetic counselling, and treatment.

Camurati-Engelmann Syndrome↗
PubMed2005

Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment.

OBJECTIVES: To determine the effects of once-weekly oral alendronate on indices of bone size, density and resorption in children with chronic illness being treated with glucocorticoids. METHODS: Twenty-two children with chronic illness treated with prednisone were randomized to receive 1 year's treatment with either once-weekly oral placebo or alendronate (1-2 mg/kg body weight) in a double-blind study. The main outcome measures were changes in lumbar spine and femoral shaft size and volumetric density (measured by dual energy X-ray absorptiometry) and N-telopeptide excretion (a marker of bone resorption). RESULTS: Once-weekly alendronate was well tolerated, and there were no major adverse events. In both groups bone size and bone mineral content increased through growth. Volumetric bone density of the lumbar spine increased significantly in the alendronate group (P = 0.013), but not in the placebo group. There were no differences between the groups in growth in the cortical width of the femoral shaft, but the cross-sectional moment of inertia per unit length-a derived estimate of mechanical strength-increased significantly in the alendronate group (P = 0.014) but not in the placebo group. Urine N-telopeptide excretion was suppressed significantly in the alendronate group (P = 0.007) but not in the placebo group. Height velocity was positively correlated with changes in both lumbar spine area and the total width of the femoral shaft (P = 0.015, P = 0.026, respectively). CONCLUSION: Once-weekly oral alendronate is well tolerated, suppresses bone resorption and may improve volumetric bone density at the lumbar spine and mechanical strength of the femoral shaft in children with chronic illness taking glucocorticoids. It does not affect bone growth. Larger controlled studies are needed to determine if these changes translate into reduced fracture incidence or greater peak bone mass. This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies.

Administration, Oral↗
PubMed2005

Lifetime risk of symptomatic carpal tunnel syndrome in Type 1 diabetes.

AIMS: To determine the lifetime risk of developing symptomatic carpal tunnel syndrome (CTS) in subjects with Type 1 diabetes and to investigate the effect of glycaemic control, body mass index (BMI), gender and age of onset of diabetes. METHODS: One hundred and twenty-two consecutive subjects with Type 1 diabetes seen by a single investigator, over 1-year, were questioned about previous surgery for, or current symptoms of CTS. Those with current symptoms were referred for nerve conduction studies (NCS). Those with previous surgery and/or diagnostic NCS were classified as having CTS. Lifetime risk was calculated by the Kaplan-Meier method. RESULTS: Twenty six out of 122 patients had CTS, 18 of whom (69%) had undergone median nerve decompression surgery. The predicted lifetime risk of CTS reached 85% after 54 years of Type 1 diabetes (95% confidence interval: 72-97%). The duration of diabetes was greater in those who had developed CTS than in those who had not (29 vs. 19 years, P=0.0001). In those diagnosed with diabetes before the age of 20 there was a lag time of at least 19 years before the development of CTS, whereas patients with later onset of diabetes, began to develop CTS from as early as 5 years diabetes duration. There was no demonstrable effect of glycaemic control, obesity, gender or retinopathy on the appearance of CTS. CONCLUSION: The lifetime risk of developing symptomatic CTS with Type 1 diabetes is high, and is related to age and duration of diabetes, but not to the development of microvascular complications.

Adolescent↗
PubMed2004

Paget's disease of bone in New Zealand: continued decline in disease severity.

We have reported previously that severe Paget's disease of bone had become less common at our center between 1973 and 1993. Data from several countries support the view that there are important secular trends in the prevalence and severity of Paget's disease. In this paper we describe recent trends in the demography of newly referred patients with Paget's disease to determine if the secular trend toward milder disease has continued. A database of all newly referred patients (n = 1487) with Paget's disease (1973 to 2002 inclusive, 30 years) was examined. Of these, 832 subjects (56%) had scintiscans. Plasma total alkaline phosphatase (total ALP) activity, disease extent on scintiscan, and a derived index of average ALP activity of pagetic bone were used as indices of severity. The number of new referrals with Paget's disease declined sharply from 1994 onward and is currently at half the rate seen 20 years earlier, while the mean age at presentation has progressively increased by 4 years per decade (P < 0.0001). Total ALP at diagnosis, disease extent on scintiscan, and the number of bones involved were all negatively correlated with both date of birth (P < 0.0001) and year of presentation (P < 0.0001), indicating that more recently born and presenting subjects had substantially less severe bone disease. The average activity of pagetic bone was only weakly correlated with year of presentation, but not with year of birth or age at presentation. Although there are a number of potential biases, these data are consistent with a continued secular trend to presentation in older subjects with less extensive skeletal involvement, and a declining prevalence of Paget's disease.

Alkaline Phosphatase↗
PubMed2004

Increasing prevalence of type 2 diabetes in adolescents.

OBJECTIVE: The rising prevalence of obesity in childhood and adolescence in North America has been paralleled by the emergence of type 2 diabetes in the adolescent age group. We have examined trends in the prevalence of type 2 diabetes in adolescents attending a diabetes clinic in Auckland, New Zealand. METHODS: Surveys of the prevalence of type 2 diabetes in attendees at the adolescent diabetes clinic at the Auckland Diabetes Centre were undertaken in 1996 and 2002. The proportion of type 2 diabetes in incident cases of diabetes diagnosed between these years was also calculated. RESULTS: The prevalence of type 2 diabetes was 1.8% (2/110) in 1996, and 11.0% (18/163) in 2002 (P = 0.008). Type 2 diabetes accounted for 12.5% (6/48) of incident cases of diabetes in the years 1997-1999, and 35.7% (10/28) of cases in the years 2000-2001, indicating a sharp rise in the incidence (P = 0.017) between the two periods. At diagnosis the mean age of the type 2 diabetes subjects was 15 years and the mean body mass index 34.6 kg/m2. Risk factors for cardiovascular disease were common in the subjects with type 2 diabetes: 85% had dyslipidaemia, 58% had increased albumin excretion rates and 28% had systolic hypertension. CONCLUSIONS: Obesity-related type 2 diabetes now accounts for a substantial proportion of newly recognized diabetes in the adolescent age group - and this proportion is escalating rapidly. Adverse cardiovascular risk factors are prevalent in this population. Public health measures to curtail the rise of obesity in childhood and adolescence are required urgently.

Adolescent↗
PubMed2002

Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy.

BACKGROUND: Ciguatera poisoning (CP) is worldwide the most common fish-borne illness and one of the most common forms of nonbacterial food poisoning. IV mannitol is considered the treatment of choice for CP but has not been evaluated in a double-blind randomized trial. METHODS: A prospective clinical study of 50 patients with CP on Rarotonga, Cook Islands, was conducted to better define the neurologic picture of CP and to study the effect of mannitol or normal saline under double-blind randomized conditions over a 24-hour period. RESULTS: The neurologic presentation of CP was that of a predominantly sensory, length-dependent polyneuropathy, with preferential small-fiber involvement. Motor paresis, cranial nerve dysfunction, and CNS abnormalities were absent but for a rare mild transitory cerebellar syndrome. At 24 hours, 96% of mannitol-treated patients and 92% of normal saline-treated patients had some improvement of symptoms (p = 1.0), whereas 12% and 24% of patients in each group were asymptomatic (p = 0.46). By 24 hours, the prevalence of the various polyneuropathic symptoms and signs was reduced roughly by half in both groups. Discomfort or pain along the vein used for infusion was more frequent in the mannitol group (84%) than in the normal saline group (36%) (p = 0.0015). CONCLUSION: Mannitol was not superior to normal saline in relieving symptoms and signs of CP at 24 hours in this study population but had more side effects. These results do not support single-dose mannitol as standard treatment for CP.

Adult↗
PubMed2002

Paget's disease in New Zealand: evidence for declining prevalence.

The prevalence rate of Paget's disease in New Zealand is believed to be among the highest in the world, but recent data suggest that it may have decreased in recent decades. We estimated the current prevalence of Paget's disease in subjects of European origin (>55 years of age) in two New Zealand cities (Dunedin and Auckland) based on review of nearly 2000 pelvic radiographs. Prevalence rate increased with age (p = 0.022) and was higher in men (p = 0.014), but there was no significant difference between the two cities. The Dunedin data were compared with a 1983 survey from the same city, and prevalence was approximately half its previous level (p = 0.012). In Auckland, the prevalence of an isolated raised plasma alkaline phosphatase level (>150 U/L, normal range <120 U/L) was estimated in over 80,000 blood samples processed at a community laboratory. The prevalence of "biochemical Paget's disease," as assessed by this surrogate marker, was very similar to that observed in the radiographic survey in Auckland for subjects <80 years of age, but not for older subjects. We conclude that the prevalence of Paget's disease in New Zealand has declined over the past two decades, indicating that there are important environmental determinants in its development. Biochemical estimates of the prevalence of Paget's disease agree well with radiographic estimates, except in the elderly. The method used herein offers an alternative way of determining the prevalence of Paget's disease.

Aged↗
PubMed2002

The osteodystrophy of mucolipidosis type III and the effects of intravenous pamidronate treatment.

Mucolipidosis type III (ML III; McKusick 252600) is a rare lysosomal storage disease in which skeletal involvement is prominent, in particular the destruction of vertebral bodies and the femoral heads. We describe studies in two siblings with ML III that suggest the presence of a distinct metabolic bone disorder. Biochemical indices of bone turnover were increased, and transiliac bone biopsy demonstrated both trabecular osteopenia and marked subperiosteal bone resorption. Intravenous pamidronate treatment given monthly for a year was well tolerated and produced dramatic clinical effects, with reduction in bone pain and improvements in mobility, despite incomplete suppression of bone resorption as assessed by biochemical, radiographic and histological criteria. Bisphosphonate therapy may have an important role in the management of bone pain in ML III, as it does in the related lysosomal disorder of Gaucher disease.

Absorptiometry, Photon↗
PubMed2002

Congenital anomalies in the offspring of women with type 1, type 2 and gestational diabetes.

AIM: To determine the frequency of major congenital anomalies in the offspring of women with gestational diabetes (GDM), classified according to their postpartum glucose tolerance status. METHODS: A prospective study of pregnancies in women with Type 1 diabetes (n = 221), Type 2 diabetes (n = 317) and GDM (n = 1822) between 1985 and 2000 (15 years). Congenital anomalies were detected by antenatal ultrasound or postnatal examination. RESULTS: The frequency of major congenital anomalies in the offspring was 5.9% (95% confidence interval (CI) 3.2-9.8) for women with Type 1 diabetes; 4.4% (95% CI 2.4-7.3) for women with Type 2 diabetes; and 1.4% (95% CI 0.9-2.0) for women with GDM. Two hundred and thirty-seven women with GDM (13%) had diabetes diagnosed on early (6-week) postpartum glucose tolerance testing. The frequency of major congenital anomalies in their offspring was 4.6% (95% CI 2.3-8.2), compared with 0.9% (95% CI 0.5-1.5) for the remainder of the GDM group (P < 0.0001). CONCLUSIONS: GDM is not a homogeneous group with regard to the risk of major congenital anomalies. In those with diabetes on early postpartum testing, who are likely to have had unrecognized Type 2 diabetes antedating their pregnancy, the rate of major congenital anomalies is the same as for women with established Type 1 or Type 2 diabetes. In the remainder of the GDM group, the rate does not differ from the non-diabetic background rate.

Blood Glucose↗
PubMed2002

Hypertensive disorders of pregnancy in women with Type 1 and Type 2 diabetes.

AIMS: Hypertensive disorders in pregnancy are common in women with Type 1 diabetes and can be associated with adverse fetal outcomes, but little is known about hypertension in pregnancy in women with Type 2 diabetes. The aim of this study was to compare the incidence and outcomes of, and risk factors for, hypertension in pregnancy in women with Type 1 and Type 2 diabetes. METHODS: One hundred consecutive singleton pregnancies in women with Type 2 and 100 in women with Type 1 diabetes were studied. Hypertension in pregnancy was classified according to Australasian Society for the Study of Hypertension in Pregnancy guidelines. Outcomes of pregnancy examined included birth weight, rates of caesarean section, premature delivery and special care unit admission, and perinatal mortality. RESULTS: The overall incidence of hypertension in pregnancy was similar in Type 2 and Type 1 diabetes (41% vs. 45%), but the distribution of subtypes differed (P = 0.028). Women with Type 2 diabetes had more chronic hypertension (diagnosed at < 20 weeks gestation), but less preeclampsia than women with Type 1 diabetes. Hypertension in pregnancy was strongly associated with a number of adverse outcomes, but the impact of hypertension was significantly less for Type 2 diabetes than it was for Type 1 (premature delivery, P < 0.005; admission to Special Care Unit, P < 0.01; caesarean section, P = 0.05). This was, in part, because the frequency of adverse outcomes was greater in women with preeclampsia. Nulliparity, poor glycaemic control at presentation, and early pregnancy blood pressure and not smoking were risk factors for hypertension of similar magnitude in both types of diabetes. Significant effects of duration of diabetes and obesity were not seen in Type 2 subjects, but were in Type 1 (P < 0.01, P < 0.05, respectively). Early pregnancy albumin excretion rate was increased more frequently in Type 2 subjects than in Type 1 (P < 0.035), but was less strongly associated with the development of preeclampsia (P < 0.035). CONCLUSIONS: The incidence of hypertension in pregnancy is similar in Type 2 and Type 1 diabetes, but the different population characteristics are reflected in a significantly different pattern of types of hypertension. Hypertension has less impact on adverse outcomes in Type 2 diabetes. Some risk factors for hypertension also differ between Type 2 and Type 1 diabetes.

Adult↗
PubMed2001

Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.

It has been claimed that the bisphosphonate space, a scintigraphic technique which simultaneously estimates bone uptake and renal clearance of bisphosphonate, can be used to predict the dose of bisphosphonate required to induce biochemical remission in Paget's disease. In a prospective study of 15 newly diagnosed patients with Paget's disease, bisphosphonate space measurements were made prior to treatment with intravenous clodronate. Treatment with clodronate 0.6 g was given four times weekly until the alkaline phosphatase (ALP) suppressed below the upper level of the reference range (120 u/l) or reached a plateau, and the cumulative dose required (1.8-7.8 g) was calculated. Overall, the bisphosphonate space correlated poorly with the total dose requirement (r = 0.441, P = 0.100), but the relationship was weakened by an outlier, who had the poorest renal function. Excluding this subject improved the correlation coefficient (r = 0.852, P <0.0001). The relationship between dose requirement and log10 initial ALP was not as strong (r = 0.672, P <0.01). However, for both ALP and the bisphosphonate space the 95% prediction intervals were wide. We conclude that the bisphosphonate space does relate to dose requirements for intravenous bisphosphonates, but that it is unreliable when renal function is poor, and may not offer much gain over the pretreatment ALP levels. Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement.

Aged↗
PubMed2001

LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.

In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Genomewide search in familial Paget disease of bone shows evidence of genetic heterogeneity with candidate loci on chromosomes 2q36, 10p13, and 5q35.

Paget disease of bone (PDB) is a common disorder characterized by focal abnormalities of increased and disorganized bone turnover. Genetic factors are important in the pathogenesis of PDB, and previous studies have shown that the PDB-like bone dysplasia familial expansile osteolysis is caused by activating mutations in the TNFRSF11A gene that encodes receptor activator of nuclear factor kappa B (RANK); however, linkage studies, coupled with mutation screening, have excluded involvement of RANK in the vast majority of patients with PDB. To identify other candidate loci for PDB, we conducted a genomewide search in 319 individuals, from 62 kindreds with familial PDB, who were predominantly of British descent. The pattern of inheritance in the study group as a whole was consistent with autosomal dominant transmission of the disease. Parametric multipoint linkage analysis, under a model of heterogeneity, identified three chromosomal regions with LOD scores above the threshold for suggestive linkage. These were on chromosomes 2q36 (LOD score 2.7 at 218.24 cM), 5q35 (LOD score 3.0 at 189.63 cM), and 10p13 (LOD score 2.6 at 41.43 cM). For each of these loci, formal heterogeneity testing with HOMOG supported a model of linkage with heterogeneity, as opposed to no linkage or linkage with homogeneity. Two-point linkage analysis with a series of markers from the 5q35 region in another large kindred with autosomal dominant familial PDB also supported linkage to the candidate region with a maximum LOD score of 3.47 at D5S2034 (187.8 cM). These data indicate the presence of several susceptibility loci for PDB and identify a strong candidate locus for the disease, on chromosome 5q35.

Chromosome Mapping↗