The Peripheral Neuropathy Prevalence and Characteristics Are Comparable in People with Obesity and Long-Duration Type 1 Diabetes.

INTRODUCTION: Peripheral neuropathy is reported in obesity even in the absence of hyperglycaemia. OBJECTIVE: To compare the prevalence and characterise the phenotype of peripheral neuropathy in people living with obesity (OB) and long-duration type 1 diabetes (T1D). PATIENTS AND METHODS: We performed a prospective cross-sectional study of 130 participants including healthy volunteers (HV) (n = 28), people with T1D (n = 51), and OB (BMI 30-50 kg/m2) (n = 51). Participants underwent assessment of neuropathic symptoms (Neuropathy Symptom Profile, NSP), neurological deficits (Neuropathy Disability Score, NDS), vibration perception threshold (VPT) and evaluation of sural nerve conduction velocity and amplitude. RESULTS: Peripheral neuropathy was present in 43.1% of people with T1D (age 49.9 ± 12.9 years; duration of diabetes 23.4 ± 13.5 years) and 33.3% of OB (age 48.2 ± 10.8 years). VPT for high risk of neuropathic foot ulceration (VPT ≥ 25 V) was present in 31.4% of T1D and 19.6% of OB. Participants living with OB were heavier (BMI 42.9 ± 3.5 kg/m2) and had greater centripetal adiposity with an increased body fat percentage (FM%) (P < 0.001) and waist circumference (WC) (P < 0.001) compared to T1D. The OB group had a higher NDS (P < 0.001), VAS for pain (P < 0.001), NSP (P < 0.001), VPT (P < 0.001) and reduced sural nerve conduction velocity (P < 0.001) and amplitude (P < 0.001) compared to HV, but these parameters were comparable in T1D. VPT was positively associated with increased WC (P = 0.011), FM% (P = 0.001) and HbA1c (P < 0.001) after adjusting for age (R2 = 0.547). Subgroup analysis of respiratory quotient (RQ) measured in the OB group did not correlate with VPT (P = 0.788), nerve conduction velocity (P = 0.743) or amplitude (P = 0.677). CONCLUSION: The characteristics of peripheral neuropathy were comparable between normoglycaemic people living with obesity and people with long-duration T1D, suggesting that metabolic factors linked to obesity play a pivotal role in the development of peripheral neuropathy. Further studies are needed to investigate the mechanistic link between visceral adiposity and neuropathy.

A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea.

The effects of treatment of obstructive sleep apnoea (OSA) on glucose metabolism have been investigated previously with conflicting results. This study evaluated the impact of nasal continuous positive airway pressure (nCPAP) treatment of OSA on insulin sensitivity. Males with moderate/severe OSA and no significant comorbidity were randomised to a therapeutic or sham nCPAP treatment group for 1 week and then reassessed. Those who received therapeutic nCPAP were further evaluated at 12 weeks. Insulin sensitivity (K(itt)) was estimated by the short insulin tolerance test. Other evaluations included blood pressure, metabolic profile, urinary catecholamines and intra-abdominal fat. In total, 61 Chinese subjects were randomised. 31 subjects receiving therapeutic nCPAP showed an increase in K(itt) (6.6+/-2.9 to 7.6+/-3.2 % x min(-1); p = 0.017), while the 30 patients on sham CPAP had no significant change, and the changes in K(itt) were different between the two groups (p = 0.022). At 12 weeks, improvement in K(itt) was seen in 20 subjects with BMI >or=25 kg x m(-2) (median (interquartile range) 28.3 (26.6-31.5); p = 0.044), but not in the nine subjects with BMI<25 kg x m(-2), or the entire group. The findings indicate that therapeutic nCPAP treatment of OSA for 1 week improved insulin sensitivity in nondiabetic males, and the improvement appeared to be maintained after 12 weeks of treatment in those with moderate obesity.

Effect of a non-adjustable oral appliance on upper airway morphology in obstructive sleep apnoea.

BACKGROUND: To evaluate the effect of oral appliance (OA) on upper airway morphology and its relationship with treatment response in subjects with obstructive sleep apnoea (OSA). METHODS: Symptomatic OSA subjects were recruited. Non-adjustable OA was custom made. Variables examined at baseline and while wearing the device at 2 months included polysomnographic data, computed tomographic measurements of upper airway cross sectional area at level of velopharynx (VA) and hypopharynx (HA), upper airway volume, and cephalometric parameters. Treatment outcome was based on post-treatment apnoea-hypopnoea index (AHI). RESULTS: Forty patients were recruited and 23 (7 women) completed the study. They were middle-aged (49, 40-58 years) (median, interquartile range) and overweight (BMI 26, 23.3-29.5 kg/m2), with moderate OSA (AHI 26.4, 14.1-36). The overall post treatment AHI was 8.4 (2.4-12.5), with 14 (61%) patients showing good response (AHI<10), and the other 9 patients showing moderate response (>50% reduction in AHI but still 10). OA decreased the cross-sectional area of the HA (P=0.046), showed a trend of decreasing the ratio of cross-sectional area of the HA to cross-sectional area of the VA (P=0.053) and significantly increased the overall upper airway volume (P=0.006, n=11). No significant relationship between upper airway parameters and treatment outcome was identified. CONCLUSIONS: OA altered upper airway morphometry towards a profile consistent with decreased propensity to collapse, which may thus have contributed to improvement of OSA.

A negative search for a paramyxoviral etiology of Paget's disease of bone: molecular, immunological, and ultrastructural studies in UK patients.

Paget's disease of bone is a common bone disease characterized by increased and disorganized bone remodeling at focal sites throughout the skeleton. The etiology of the disease is unresolved. A persistent viral infection has long been suggested to cause the disease. Antigen and/or nucleic acid sequences of paramyxoviruses (in particular measles virus [MV], canine distemper virus [CDV], and respiratory syncytial virus [RSV]) have been reported in pagetic bone by a number of groups; however, others have been unable to confirm this and so far no virus has been isolated from patients. Here, we reexamined the question of viral involvement in Paget's disease in a study involving 53 patients with established disease recruited from seven centers throughout the United Kingdom. Thirty-seven patients showed clear signs of active disease by bone scan and/or histological assessment of the bone biopsy specimens and 12 of these had not received any therapy before samples were taken. Presence of paramyxovirus nucleic acid sequences was sought in bone biopsy specimens, bone marrow, or peripheral blood mononuclear cells using reverse-transcription polymerase chain reaction (RT-PCR) with a total of 18 primer sets (7 of which were nested), including 10 primer sets (including 3 nested sets) specifically for MV or CDV. For each patient at least one sample was tested with all primer sets by RT-PCR and no evidence for the presence of paramyxovirus RNA was found in any patient. In 6 patients, bone biopsy specimens with clear histological evidence of active disease tested negative for presence of measles and CDV using immunocytochemistry (ICC) and in situ hybridization (ISH). Intranuclear inclusion bodies, similar to those described by others previously, were seen in pagetic osteoclasts. The pagetic inclusions were straight, smooth tubular structures packed tightly in parallel bundles and differed from nuclear inclusions, known to represent MV nucleocapsids, in a patient with subacute sclerosing panencephalitis (SSPE) in which undulating, diffuse structures were found, arranged loosely in a nonparallel fashion. In the absence of amplification of viral sequences from tissues that contain frequent nuclear inclusions and given that identical inclusions are found in other bone diseases with a proven genetic, rather than environmental, etiology, it is doubtful whether the inclusions in pagetic osteoclasts indeed represent viral nucleocapsids. Our findings in this large group of patients recruited from throughout the United Kingdom do not support a role for paramyxovirus in the etiology of Paget's disease.

Absence of measles virus and canine distemper virus transcripts in long-term bone marrow cultures from patients with Paget's disease of bone.

The presence of intranuclear inclusions in pagetic osteoclasts with similar characteristics to those seen in some slow viral diseases has lead to the hypothesis that Paget's disease is caused by a similar infection. Bone marrow aspirates from seven patients with hemipelvic Paget's disease were taken from both sides of the pelvis and cultured under identical conditions. RNA was extracted after approximately 2 weeks of culture and reverse transcriptase-linked polymerase chain reaction used to investigate the expression of measles and canine distemper virus RNA. We were unable to detect the presence of measles virus (MV) or canine distemper virus (CDV) transcripts in bone marrow cultures from either affected or unaffected sites in any of our patients. The results of this study do not support a role for MV or CDV in the pathogenesis of Paget's disease of bone.

Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0.75) was observed when PTH was lagged by 1.5 h in healthy individuals, suggesting that changes in phosphate precede changes in PTH concentration. PTH/CT(x) and PTH/PINP showed maximum correlation when CT(x) (r = 0.68) and PINP (r = 0.71) were lagged by 3 h. In AGHD patients, compared to controls the maximum correlation between PTH/phosphate (r = 0.88, P = 0.007), PTH/CTx (r = 0.61, P = 0.027), and PTH/PINP (r = 0.65, P = 0.028) was observed when the lag time was reduced by 1.5 h in all variables, with changes in PTH and phosphate occurring at concurrent time points. Our data suggest decreased end-organ sensitivity to the effects of PTH in AGHD patients, resulting in a significantly lower NcAMP, low bone turnover, and higher calcium excretion in the presence of significantly higher PTH concentrations. We have also demonstrated that changes in serum phosphate precede those of PTH, which in turn precede changes in bone resorption and formation in healthy individuals. This relationship was altered in AGHD patients. These results suggest a possible role for GH in regulating PTH secretion and the bone remodeling process.

Hodgkin's disease with primary manifestation in the liver.

We describe a patient with HD presenting with hepatomegaly and impaired liver function and discuss the differential diagnosis and histologic diagnosis of HD in the liver.

The relationship between mediastinal lymph node attenuation with parenchymal lung parameters in silicosis.

OBJECTIVE: Attenuation changes on computed tomography (CT) in mediastinal lymph nodes (LN) may be related to lung alterations and functional impairment in silicosis. DESIGN: CT and clinical data of 41 (64.2 +/- 8.3 years) males with silicosis were retrieved. Attenuation type (calcified, hyperdense, normodense) and calcification pattern (central, eccentric, dense, eggshell, speckled) of mediastinal LN were evaluated; LN attenuation of uncalcified LNs quantified on CT in six LN stations. Nodular profusion (CT-NP) and progressive massive fibrosis (CT-PMF) were graded. Relationships between LN, CT, lung function and clinical parameters were determined. RESULTS: LN sites were paratracheal (n = 39), subcarinal (n = 39), tracheobronchial (n = 37), aortopulmonary (n = 37), hilar (n = 27), and peri-oesophageal (n = 21). LNs were calcified, hyperdense and normodense in 107, 85 and 54 LN stations, respectively. Uniformly calcified LN was most common, followed by speckled calcification. Central, eccentric and eggshell calcification was rare. CT-NP scores > or = 16 were associated with higher LN attenuation and number of calcified LN stations than CT-NP scores < 16. PMF had no influence over LN morphology or calcification pattern. LN attenuation correlated with CT-PMF (r = 0.36, P = 0.01), CT-NP (r = 0.54, P < 0.001) and DLCO/VA (r = -0.33, P = 0.02). CONCLUSION: Uniformly calcified and hyperdense LNs are common in silicosis, and eggshell LN calcification is rare. There are associations between LN attenuation and lung function impairment, and CT grades of nodular profusion and PMF.

Diabetes Mellitus in a Malaysian Teaching Hospital: Prevalence of Diabetes Mellitus and Frequency of Testing for Hypercholesterolaemia, Proteinuria and HbAlc.

We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the diagnoses on admission to diabetes, and the frequency of testing for HbA1c as a marker of long-term glycaemic control, proteinuria, and hypercholesterolaemia. In addition, patients with raised laboratory plasma glucose without a know history of diabetes mellitus, were studied to see if these had been further evaluation. The overall prevalence of diabetes in our hospital was 25.% with the highest prevalence found (37.8%) on medical wards. 10.5% of admissions were due directly to diabetes and a further 58.9% of patients were admitted with illness which were significant related to diabetes. Overall testing rates for HbA31c, proteinuria, and hypercholesterolaemia were less than ideal (51.6, 73.4 and 45.% respectively). Less than 50% of patients without previously diagnosed diabetes but with high plasma glucose values had further evaluation for diabetes. In conclusion, this study has detected a high overall prevalence of diabetes among inpatients in an urban Malaysian hospital. Rates of testing for HbA51c, proteinuria, and hypercholesterolaemia, are disappointingly low, as is further evaluation of patients without known diabetes, but with elevated glucose values. More effective measures to improve the delivery of inpatient diabetes care are needed.

The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer.

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer. Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination. Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91 versus 58%) at detecting these lesions, but less specific (26 versus 50%). A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.

Paget's disease of bone.

Paget's disease of bone is a relatively common condition in the UK affecting up to 5% of the population over the age of 55 years with particularly high prevalence in the North West of England. The majority of those affected are asymptomatic. Its precise cause remains unknown, and until recently, choice of treatment of this sometimes painful and debilitating disease has been limited. In this article, we review various aspects of this disease, concentrating particularly on recent advances in our understanding of its aetiology and its treatment.

Treatment of severe proliferative retinopathy and diabetic maculopathy.

Strict blood glucose control, early detection and surveillance of diabetic retinopathy by means of validated screening programmes, and judicious use of laser photocoagulation can greatly reduce the risk of visual loss in diabetes. Some patients however, have aggressive neovascular disease resistant to laser treatment, or present at a late stage with advanced fibroproliferative disease, and may progress rapidly to blindness. In the elderly with Type 2 disease, diabetic maculopathy is more common and requires a different therapeutic approach. The present article describes two diabetic patients and discusses the management of patients with severe proliferative retinopathy or diabetic maculopathy.

Incidence of diaphragmatic paralysis following supraclavicular brachial plexus block and its effect on pulmonary function.

Thirty unpremedicated ASA physical status 1-3 patients aged between 18 and 69 years, scheduled for upper limb surgery, received a conventional supraclavicular brachial plexus block using a nerve stimulator and bupivacaine 0.375% 0.5 ml.kg-1. Spirometric measurements of pulmonary function and ultrasonographic assessments of diaphragmatic function were made before the block and at 10-min intervals after injection until full motor block of the brachial plexus had developed. Complete paralysis of the ipsilateral hemidiaphragm occurred in 50% of patients. Seventeen per cent of patients had reduced diaphragmatic movement and the rest (33%) had no change in diaphragmatic movement. Those with complete paralysis all showed significant decreases in pulmonary function, whereas those with reduced or normal movement had minimal change. All patients remained asymptomatic throughout, with normal oxygen saturation on room air.

Confluent hepatic fibrosis in monozygotic twins.

The MRI and CT features of confluent hepatic fibrosis (CHF) are reported in two 6-year-old twins. This is the first case report in children of this little known entity, which may mimic mass lesions, and the first to describe an association of CHF with anti-tuberculous drugs.

Disseminated zoster, hyponatraemia, severe abdominal pain and leukaemia relapse: recognition of a new clinical quartet after bone marrow transplantation.

Reactivation of varicella-zoster virus (VZV) is one of the commonest complications after stem cell transplantation, and often presents with atypical manifestations. We describe two unusual cases of occult disseminated zoster in allogeneic stem cell transplant recipients, presenting as severe abdominal pain and syndrome of inappropriate antidiuretic hormone secretion/hyponatraemia, and accompanied by leukaemia relapse. There was complete clinical recovery with high-dose aciclovir and intravenous immunoglobulin. Prompt treatment of leukaemia relapse also resulted in complete remission. A possible immunological link between concurrent breakdown of immune control of VZV and leukaemia is discussed.

Adult croup: a rare but more severe condition.

We report the first adult patient with virologically confirmed croup caused by parainfluenza virus type 3 and review 10 cases of adult croup described in the English-language literature. Circumstantial evidence of viral infection was present in only 1 other case, in which there was a rise in antibody titer against influenza B virus. Ten patients (91%) required intensive care support. None of the 11 patients died. A comparison was also made between the 11 adults with croup and 43 children hospitalized with severe croup described in a representative paper published in 1984. Adult croup represents an apparently more severe disease entity than pediatric croup.

Mature teratomas of the adrenal gland: imaging features.

BACKGROUND: We describe the imaging features of three, histologically confirmed, mature teratomas of the adrenal gland not described previously in the radiologic literature and discuss the differential diagnosis of lipomatous tumors of the adrenal gland. METHODS: Computed tomographic (n = 3), magnetic resonance imaging (n = 1), and sonographic (n = 1) features were reviewed retrospectively and the findings correlated with gross pathology and histology. RESULTS: There were two females (age 8 and 18 years) and one male (age 17 years). Tumor size ranged from 5 to 11 cm (mean = 7.3 cm). All tumors were well circumscribed and contained fat components. Calcification was demonstrated in two tumors and was the predominant component in one. Only one was cystic. CONCLUSION: The radiologic features of these tumors were typical of mature teratomas occurring elsewhere in the body. This should be considered in the differential diagnosis of lipomatous tumors of the adrenal gland, especially in children and adolescents.

Ultrasonography of intra-abdominal cystic lesions in the newborn.

Intra-abdominal cystic lesions are increasingly recognized in the newborn because of the advent of routine antenatal ultrasonography. As these lesions are often asymptomatic or non-specific in clinical presentation in the newborn, imaging by ultrasonography has an important role in diagnosis. We present a pictorial review of the commonly encountered intra-abdominal cystic lesions in the newborn, with emphasis on ultrasonographic features that can aid differentiation between the various lesions.