Effects of Age,Sex, and Polycystic Disease on Progressive Bone Disease of Renal Failure

A study of 150 patients undergoing haemodialysis has shown that age had a striking effect on the radiological presentation of renal bone disease, erosions being common in the young and uncommon in older patients and vascular calcification showing opposite trends to this. Men aged 20 to 59 years had a greater tendency to develop erosions than did women in this age range. Examination of a group of 53 patients over a period of five years showed that the half time for the development of vascular calcification was 4·6 years, erosions 26·7 years, and fractures 6·9 years. Nine out of 16 polycystic patients matched for age and sex with 50 controls did not develop erosions and had consistently less vascular calcification than the controls when examined over a six-year period.     

Fat Embolism in Patients with Fractured Hips

Fat embolism was assessed at necropsy and correlated with clinical findings in the patients who died among 854 with fractured hips admitted to hospital between 1967 and August 1971. Sixteen cases of clinical importance were found, eight of which were judged to have been fatal or to have seriously contributed to death. Frequencies were as follows: 2·4 to 3·3% among 424 patients with subcapital fractures; 0·7 to 0·8% in the 405 with trochanteric fractures; 4·1 to 7% among subjects treated without operation, representing 30% of those who died within seven days; and 0·9 to 1·1% among patients treated by pinning, nailing, or nail-plating. The higher frequency in the conservatively treated group is probably related to selection of poor-risk subjects. Fat embolism was found in 6·8 to 8·0% of those with subcapital fractures treated by primary Thompson''s arthroplasty which utilizes acrylic cement, and in none of those given Moore''s prostheses for which cement is not used. Study of a larger group after Moore''s prosthesis is required to establish its lack of special risk. Fat embolism accounted for all the deaths within seven days of Thompson''s arthroplasty and for most within 14 days; it was clearly related to surgery in some cases.A possible explanation of the hazard of Thompson''s arthroplasty is that fat globule entry is enhanced by a rise of intramedullary pressure due to proximal occlusion of the reamed marrow cavity. A controlled trial of the effect of venting the marrow cavity on the frequency of fat embolism is warranted. It is possible that the acrylic monomer may also contribute to venous entry of medullary fat. The higher-age group of those with subcapital fractures and associated chronic cardiac and pulmonary disease might make them more susceptible to fat embolization than those in whom arthroplasty is also carried out for chronic hip disease.     

Operative Treatment of Terrible Triad of the Elbow via Posterolateral and Anteromedial Approaches

The aim of the study was to explore the clinical outcome of posterolateral and anteromedial approaches in treatment of terrible triad of the elbow. The study involved 12 patients with closed terrible triad of the elbow treated by posterolateral and anteromedial approaches between January 2010 and June 2012. The mechanism of injury included fall from height in 9 patients and traffic accident in 3. According to O’Driscoll classification for fractures of the ulnar coronoid, there were 11 patients with type Ⅰ and 1 with type Ⅱ fractures. According to Mason classification for fractures of the radial head, there were 3 patients with type Ⅰ, 7 with type Ⅱ and 2 with type Ⅲ fractures. All patients were followed up for 12-27 months (average 15.5 months), which showed no pain or severe pain in all patients except for 2 patients with mild pain. At the last follow-up, the mean flexion was for 125°(range, 90°-140°), the mean extension loss for 20°(range, 0°-70°), the mean pronation for 66°(range, 20°-85°) and the mean supination for 60°(range, 30°-85°). The bony union time was 8-14 weeks (average 11 weeks) and the elbows were stable in flexion-extension and varus-valgus in all patients. The elbows maintained a concentric reduction of both the ulnotrochlear and the radiocapitellar articulation. Mild heterotopic ossification of the elbow occurred in 3 patients at 6 months after operation and mild degenerative change in 1 patient at 18 months after operation. The Broberg and Morrey elbow performance score was 82 points (range, 58-98 points). The results were excellent in 6 patients, good in 4, fair in 1 and poor in 1, with excellence rate of 83.3%. The results showed that the combined posterolateral and anteromedial approaches can facilitate the reduction and fixation of terrible triad of the elbow. Repair of radial head, coronoid, medial and lateral collateral ligaments can sufficiently restore the elbow stability, allow early postoperative motion and enhance the functional recovery.     

Circulating S100A12 Levels Are Associated with Progression of Abdominal Aortic Calcification in Hemodialysis Patients

Vascular calcification is an important factor associated with mortality in dialysis patients. Recently, soluble receptor for advanced glycation end product (sRAGE) and extracellular RAGE binding protein S100A12 (EN-RAGE) have been reported to be involved in the process of vascular calcification. Therefore, we investigated whether sRAGE and S100A12 are useful indicators of progression of abdominal aortic calcification in hemodialysis (HD) patients. We analyzed annual changes in vascular calcification score (VCS) for up to 4 years, compared to clinical and biological parameters in 149 HD patients. VCS was assessed annually using plain X-ray images of the lateral lumbar spine. The progression group was defined as patients with an increase in VCS more than 1 point each year on average during the observation period. Time-averaged concentrations were also evaluated to examine the association between biological parameters and changes in VCS. The patients had a mean age of 58.59 ± 12.93 years; 53.7% were male, and 45% were diabetic. The VCS increased in 55 patients; the mean increase was 1.60 ± 2.91 points. In a stepwise multivariate logistic analysis, we found that higher levels of S100A12 were significantly associated with progression of VCS (odds ratio [OR], 2.622; 95% confidence interval [CI], 1.371–5.016; P = 0.004). The relationship between sRAGE and VCS was not statistically significant (OR, 0.644; 95% CI, 0.302–1.374; P = 0.255). Our findings suggest that serum levels of S100A12 are associated with progression of abdominal aortic calcification in HD patients, independent of sRAGE level.     

Factors protective against retinopathy in insulin-dependent diabetics free of retinopathy for 30 years

To investigate which factors might protect against the development of retinopathy 40 insulin-dependent diabetics who had remained free from retinopathy despite diabetes of long duration (mean±1 SD 30±10 years) were compared with 40 patients who had background and 47 who had proliferative retinopathy (mean durations of disease 16±5 and 19±5 years respectively). The three groups had had similar mean ages at onset of diabetes. The mean of all postprandial blood glucose measurements at hospital clinics from diagnosis of diabetes to detection of retinopathy, or to the most recent negative eye examination, was 9·9±2·1 mmol/l (178±38 mg/100 ml) in the group with no retinopathy, 11·8±2·1 mmol/l (213±38 mg/100 ml) in those with background retinopathy, and 12·4±2·1 mmol/l (223±38 mg/100 ml) in those with proliferative retinopathy (p <0·0001). This difference was not reflected in present concentrations of haemoglobin A_1C, probably because glycaemic control had been improved after the development of retinopathy. In the groups with background and proliferative retinopathy there were significant negative correlations between mean blood glucose concentrations and the number of years that had elapsed from diagnosis of diabetes to detection of retinopathy, suggesting that the development of both grades of retinopathy depends on the degree and duration of glycaemic exposure.The patients with no retinopathy had attended clinic more frequently (p <0·025), more of them had required emergency hospital treatment for hypoglycaemia (p <0·0025), and they tended to have had a lower prevalence of hyperglycaemic coma than the other groups. Although mean percentage ideal body weight and diastolic blood pressure were lower in the patients with no retinopathy at the time of study, mean body weight, blood pressure, and the prevalence of smoking in the years before the development of retinopathy had been similar in all groups, suggesting that these did not influence the development of retinopathy.     

A new urethral catheter

A new balloon catheter for women with a flexible urethral portion that conforms to the shape of the closed urethra was tested. In sheep control catheters caused epithelial destruction, which was absent with the conformable catheter. A 12 week crossover trial compared control catheters in 52 long stay geriatric patients. Eighty two out of 91 conformable catheters were rated as comfortable compared with 68 of 87 control (p=0·006). The average length of time in situ was 15·9 days for the conformable catheter compared with 12·9 days for the control (p=0·001). The average number of bypasses a week with the conformable catheter was 1·1 compared with 1·3 for the control; this difference was not significant. Examination of 249 used catheters showed significantly fewer with intraluminal obstruction with struvite among the conformable than control catheters (1 (0·8%) versus 15 (11·5%); p<0·001).This new catheter for women is a substantial improvement over the Foley catheter and (except in urethral stricture) is suitable for all forms of drainage.     

Surgical Treatment of Severe Attacks of Ulcerative Colitis,with Special Reference to the Advantages of Early Operation

The management and outcome of 258 severe attacks of ulcerative colitis from 1952 to 1969 has been reviewed. If remission did not occur during an initial course of intensive medical treatment, including administration of corticosteroids, operation (generally ileostomy with proctocolectomy or subtotal colectomy) was performed. This took place some 12 to 17 days after admission as a rule during the years 1952-63, but usually within five to seven days from 1964 to 1969.Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4·8% in the former and 0·7% in the latter, the operative mortality 20·0 and 7·0%, and the overall mortality 11·3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32·5%) than in the second (11·1%). The immediate mortality of all such operations was 11·6%; in cases with perforation it was 28·6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18·5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37·1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn''s disease in 17 instances.     

Effect of manganese on calcification of bone

1. Young mice were maintained on a basal diet composed of meat, which is poor in both manganese and calcium. 2. The addition of small amounts (2·5–5·0mg./kg. of meat) of manganese improved weight gain and calcification of bone and decreased incorporation of injected radiocalcium into bone. 3. Prolonged treatment with larger amounts (10·0–25·0mg./kg. of meat) of manganese depressed growth, induced defective calcification of bone and increased incorporation of radiocalcium into bone.     

Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

Experimental studies suggested that statins attenuate vascular AT₁ receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00154024","term_id":"NCT00154024"}}NCT00154024     

Impact of Renal Sympathetic Denervation on Left Ventricular Structure and Function at 1-Year Follow-Up

Background

Catheter-based sympathetic renal denervation (RDN) is a recent therapeutic option for patients with resistant hypertension. However, the impact of RDN in left ventricular (LV) mass and function is not completely established. Our aim was to evaluate the effects of RDN on LV structure and function (systolic and diastolic) in patients with resistant hypertension (HTN).

Methods and Results

From a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up echocardiogram were included in this analysis. Mean age was 65±7 years, 48% were males, 71% had type 2 diabetes. Most had hypertension lasting for more than 10 years (90%), and were being treated with a median number of 6 anti-hypertensive drugs, including 74% on spironolactone. At 1-year, there was a significant decrease both on office SBP (176±24 to 149±13mmHg, p<0.001) and DBP (90±14 to 79±11mmHg, p<0.001), and also in 24h ABPM SBP (150±20 to 132±14mmhg, p<0.001) and DBP (83±10 to 74±9mmHg, p<0.001). There was also a significant decrease in LV mass from 152±32 to 136±34g/m² (p<0.001), an increase in LV end diastolic volume (93±18 to 111±27 mL, p = 0.004), an increase in LV ejection fraction (65±9 to 68±9%, p = 0.001) and mitral valve E deceleration time (225±49 to 247±51ms, p = 0.015) at 1-year follow up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups.

Conclusions

In this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and ABPM blood pressure and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up.     

Exchangeable and Total Body Potassium in Patients with Chronic Renal Failure

Total body potassium determined by whole-body monitoring and exchangeable body potassium estimated with ⁴³K were measured simultaneously in 12 patients with stable chronic renal failure. Values for the exchangeable potassium were obtained after equilibration periods of 24, 48, and 64 hours. The exchangeable body potassium, expressed as a percentage of the total body potassium (mean ± S.E. of mean), gave values of 60·7 ± 3·3%, 83·6 ± 2·7%, and 85·9 ± 2·7% at 24, 48, and 64 hours respectively. It seems that the equilibration between radioactive and native potassium is incomplete after 24 hours; and that exchangeable potassium measured at this time is not an accurate index of the status of total body potassium in such patients. Furthermore, the finding that the value at 64 hours is significantly less than found in healthy subjects suggests that the exchangeable potassium is a smaller fraction of the total body potassium in patients with chronic renal failure.     

Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients

The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9·0 (95% confidence interval 2·2 to 80·0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14·5 (95% confidence interval 1·9 to 112·3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol.Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients.     

Plasma TSH and Serum T-4 Levels in Long-term Follow-up of Patients Treated with 131I for Thyrotoxicosis

In February 1972 58% of patients euthyroid after iodine-131 therapy given for thyrotoxicosis between 1954 and 1966 had a high plasma TSH (>7·4 μU/ml) and 42% a normal plasma TSH level. A group of 69 of the euthyroid patients with high plasma TSH levels (25·0±2·0 μU/ml) in 1972 were re-examined 15 and 24 months later. The mean plasma TSH in the 66 patients remaining euthyroid at 15 months was 22·6±1·8 μU/ml, while three patients had become hypothyroid. At 24 months 64 of the patients were still available for study, of whom 61 remained euthyroid with a mean plasma TSH of 21·6±2·0 μU/ml, and a further three had become hypothyroid.All of a group of 61 of the euthyroid patients with normal plasma TSH levels (4·0±0·2 μU/ml) in 1972 remained euthyroid at 24 months with a mean plasma TSH of 4·1±0·3 μU/ml, though the plasma TSH level had become slightly raised in three.The mean serum T-4 level in the euthyroid patients with a high plasma TSH was significantly lower, though still in the normal range, than that in the euthyroid patients with a normal plasma TSH both in 1972 and in 1974.Since no patient with a normal plasma TSH level after iodine-131 treatment six to 18 years earlier for thyrotoxicosis developed hypothyroidism over a two-year period, the follow-up of such patients need not be so rigorous as that of similarly treated euthyroid patients with raised plasma TSH levels in whom hypothyroidism developed at the rate of 5% per year.     

Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study

Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early post-menopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial. Treatment with hormones significantly reversed the vertebral bone loss. The net gain in vertebral bone density amounted to 6·4% a year with continuous supplementation and 5·4% a year with sequential supplementation; the net gain in forearm bone density was lower (3·6% with continuous and 3·7% with sequential supplementation).Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones, administered over several years, are needed.     

Is dialysis hypotension caused by an abnormality of venous tone?

The role of peripheral vascular tone in the development of hypotension induced by dialysis was investigated in eight patients undergoing haemodialysis with acetate or bicarbonate buffered fluid. Each patient had two sessions of dialysis with acetate fluid and two with bicarbonate fluid in the order acetate, bicarbonate, bicarbonate, acetate or bicarbonate, acetate, acetate, bicarbonate. Mean arterial blood pressure fell at a mean rate of 3·9 mm Hg/hour during dialysis with acetate fluid and 1·4 mm Hg/hour during dialysis with bicarbonate fluid. The rate of fall was significantly greater during dialysis with acetate fluid compared with bicarbonate fluid. Heart rate increased by a mean rate of 2·6 beats/min/hour during dialysis with both acetate and bicarbonate fluid. Vascular resistance in the forearm increased at a rate of 3·6 units/hour during dialysis with acetate fluid and 4·5 units/hour during dialysis with bicarbonate fluid, but the venous bed of the forearm dilated. The index of venous tone rose at a mean rate of 0·23 ml/100 dl over 40 mm Hg/hour during dialysis with acetate fluid and 0·20 ml/dl over 40 mm Hg/hour during dialysis with bicarbonate fluid.Inappropriate peripheral venodilatation may be important in the development of hypotension induced by dialysis.     

Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy

Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.     

Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal urinary albumin excretion (<30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion >300 mg/24 h). Ten non-diabetic subjects matched for sex, age, and physical activity served as controls. Oxygen uptake was similar in the four groups at rest and during a 75 W workload. Maximal oxygen uptake was also similar in the control subjects and group 1 (median 41·7, (range 29·1-53·0) ml/kg/min v 38·5 (26·6-59·2) ml/kg/min, respectively), but was significantly lower in group 2 (27·7 (13·9-44·3) ml/kg/min) and group 3 (26·8 (22·6-36·7) ml/kg/min). The difference in maximal oxygen uptake between groups 1 and 2 was 10·8 ml/kg/min (95% confidence interval 3·6 to 23·4 ml/kg/min) and between groups 1 and 3, 11·7 ml/kg/min (4·9 to 22·5 ml/kg/min). These differences were not explained by differences in metabolic control or the degree of autonomic neuropathy.Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established.