Hyperthyroidism in the Land of Graves: Results of Treatment by Surgery, Radio-iodine and Carbimazole in 837 Cases

A review of the outcome of treatment by subtotal thyroidectomy,radio-iodine and carbimazole of 837 patients with hyperthyroidismseen consecutively over the period 1954–78 inclusive ispresented. The age and sex distribution, the male to femaleratio, the ABO blood group distribution and the prevalence ofpernicious anaemia and diabetes mellitus in these patients wasalso analysed. Life-table data showed that the five-year andten-year cumulative relapse rates following a two-year courseof carbimazole (n = 162) were 56 per cent and 62 per cent; followingsurgery (n = 266), 6 per cent and 10 per cent and followingradio-iodine (n = 43), 3 per cent and 14 per cent. Five-yearand ten-year cumulative hypothyroid rates after surgery were10 per cent and 18 per cent, and after radio-iodine 10 per centand 30 per cent. Hypothyroidism did not occur after carbimazoletherapy. Of 31 patients who took carbimazole for less than twoyears (mean 11 months, range 6–19 months), 91 per centhad relapsed at five years. Of 79 patients treated for longerthan two years (mean 3.8 years, range 2–14 years), relapserates at five and eight years were 49 per cent and 62 per cent.Nine patients (3.4 per cent) suffered permanent vocal cord paralysisand five (1.9 per cent) had permanent hypocalcaemia. The male/female ratio was 9.9 to 1, with a peak female prevalencebetween 25 and 30 years and a peak male prevalence between 40and 45 years. The ABO blood group distribution among patients did not differsignificantly from the distniution in the general population(x² = 13.4, p = 0.2). Forty-seven patients (5.6 per cent) had diabetes mellitus andthyrotoxicosis whilst two patients (0.23 per cent) had diabetes,thyrotoxicosis and pernicious anaemia.     

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years(mean±SEM) with chronic renal failure of varied aetiologywere randomized to receive either a conventional low proteindiet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphatediet (providing approximately 1000 mg phosphate plus an orallyadministered phosphate binder, minimum protein intake 0.8 g/kg/day;n=30) or to control (minimum protein intake 0.8 g/kg/day, nophosphate restriction; n=32). Patients were reviewed for a minimumof 6 months before randomization and were withdrawn from thestudy if plasma creatinine exceeded 900 µmol/1, plasmaphosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an averageof 19±3 months. Mean plasma creatinine rose from 398±33to 600±50 µmol/1. Dietary protein intake was estimatedat 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05in the low phosphate and 1.14±0.05 in the controls, phosphateintake was 815±43, 1000± 47, and 1315±57mg/day, respectively. Urinary urea excretion and protein catabolicrates were significantly reduced (p<0.01) only in those onprotein restriction, at 213±9 mmol/24 hours and 0.71g/kg/day, respectively. Phosphate excretion was significantlylower (p<0.05) in both the low protein group (17.9±0.8mmol/24 hours) and the low phosphate group (18.6±1.0mmol/24 hours) compared to controls. Changes in body weight,muscle mass and serum transferrin, albumin and immunoglobulinswere comparable between the groups. Mean blood pressure followingrandomization was 150/89±3/1 (low protein), 148/87±3/1(low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall ofcreatinine clearance (ml/min/ 1.73 m²/month), by rate of deteriorationderived from reciprocal plasma creatinine against time plots(1/mmol/year) and to assess individual patient's response totreatment by two phase linear regression (‘breakpoint’)analysis of reciprocal plasma creatinine/time plots. Progressionwas analysed only in patients seen for at least 3 months followingrandomization. The rate of fall of creatinine clearance was not significantlydifferent between the groups (ANOVA): 0.56±0.08 ml/min/1.73m2/month (low protein, n=28), 0.44±0.07 (low phosphate,n=23) and 0.69±0.11 (control, n=27). In 50 patients (18low protein, 16 low phosphate and 16 control) whose rate ofprogression could be calculated before and after randomization,there was a fall in rate of progression averaging 0.18 ml/min/1.73m2/month in those on low protein diet and those on low phosphatediet, but a rise of 0.08 in the controls. These differenceswere, however, not statistically significant. Similar resultswere obtained when the rates of deterioration were calculatedfrom plasma creatinine. Significant individual improvements(p<0.01) in rates of progression by ‘breakpoint’analysis occurred in 17 patients: six on low protein, sevenon low phosphate and in four controls. Sixty-one (72 per cent)of the patients examined by this method showed no significantchange in the rate of progression while seven patients had acceleratedprogression. There was no difference in the requirement formaintenance dialysis facilities between groups. No significant benefit of protein and phosphate restrictionwas therefore demonstrated.     

Plasmodium falciparum Hyperparasitaemia: use of Exchange Transfusion in Seven Patients and a Review of the Literature

During the last 15 years, at least 35 patients with severe falciparummalaria or babesiosis have recovered following treatment byexchange of up to 10 1 of blood. In a patient treated in Manchester,a parasitaemia of 2.10 x 10⁶ µl (42 per cent) was virtuallyeliminated over eight hours by a 3.5 litre exchange blood transfusion.However, the equipment and amounts of compatible blood requiredfor total exchange are rarely available in areas endemic formalaria and the risks of the procedure, including transfusion-relatedinfections, are high. Partial exchange transfusion with oneto two litres of blood carried out over two to seven hours,reduced Plasmodium falciparum parasitaemias of 0.33–1.48x 10⁶/µl (13–38 per cent) to 0.11–0.81 x 10⁶(4–17 per cent) in six Thai patients who were receivingintravenous quinine. The reduction in parasitaemia ranged from0.13–0.67 x 10⁶ µl (9–12 per cent) withinsix hours. During the same period, parasitaemia in 13 patientswith cerebral malaria treated with chemotherapy alone showedlittle reduction from initial levels of 0.20–1.74 x 10⁶/µl(11–42 per cent). One of the patients who were treatedwith exchange transfusion died with intractable hypotensionbefore the procedure could be completed and two others developedoliguric renal failure which was controlled by peritoneal dialysis.Partial exchange transfusion is a promising and practical alternativeto total exchange where facilities are limited. It deservesfurther assessment in the rural tropics.     

Final Outcome of Ursodeoxycholic Acid Treatment in 126 Patients with Radiolucent Gallstones

One hundred and twenty-six patients with radiolucent gallstonesin ‘functioning’ gallbladders were treated with8–10 mg ursodeoxycholic acid (UDCA) Kg/day and followedto a treatment conclusion. Complete or partial gallstone dissolutionwas achieved in 74 (59 per cent). However, only 22 achievedcomplete gallstone dissolution, as judged by two normal oralcholecystograms; ultrasonograms were performed in 16 of thesepatients, and all were normal. UDCA was stopped in 76 patients:because of cystic duct obstruction (n=12), severe biliary pain(n=13), non-response (n=25) or partial stone dissolution witharrested progress (n=26). Life-table analysis showed that completegallstone dissolution rates at four years were 25–30 percent. (two normal oral cholecystograms) and 17–19 percent (two normal oral cholecystograms plus one ultrasonogram).All patients with complete gallstone dissolution had shown partialstone dissolution at 6–12 months; of those with partialstone dissolution at six months, only 25 per cent went on tocomplete gallstone dissolution, and then always within two years.Efficacy correlated inversely with stone size but not with age,sex, obesity or on-treatment saturation indices. Acquired surfacegallstone calcification developed in 13 patients (life-tableanalysis 22±7 per cent at four years); none of thesepatients achieved complete gallstone dissolution and only fiveachieved partial stone dissolution. Thus, despite relativelyhigh partial gallstone dissolution rates, the ultimate efficacyof UDCA in achieving complete gallstone dissolution is low.     

Prognostic significance of the neutrophil count in immunocompetent patients with bacteraemia

To examine the prevalence of neutropaenia in immunocompetent,bacteraemic patients, and whether it carries an independentrisk for mortality, we surveyed 2096 bacteraemic patients withoutmalignant diseases, and who were not receiving cytotoxic drugs.The granulocyte count on the day of the first positive bloodculture was < 1 x10⁹ cells/l in 33 patients (1.7%, group1); 1.0–4.0 x 10⁹ cells/l in 154 patients (7.9%, group2); 4.0–8.0 x 10⁹ cells/l in 564 patients (29%, group3); 8.0–;20.0x10⁹ cells/; in 1034 patients (53%, group4); and >20.0x10⁹ cells/l in 163 patients (8.4%, group 5).The mortality rates in the five groups were 39.4%, 18.8%, 18.1%,25.7% and 25.8%, respectively (p=0.0001). The main pathogensin group 1 were Staphylococcus aureus in 25% of patients andPseudomonas sp. in 23%. Mortality in group 1 patients was higherthan in the other patients (odds ratio 1.4, 95% Cl 1.1–1.9).Mortality was also significantly higher in group 2 patientswith high blood urea nitrogen. The percentage of neutropaenic,septic patients without known risk factors for neutropaeniais small, but their mortality is high. Overall mortality inpatients with relative neutropaenia (1.0–4.0x10⁹ cells/l)is low, but a subgroup of patients with high blood urea nitrogenis at considerable risk for a fatal outcome. High leucocytecounts are also a marker of increased risk for mortality, butthis association is not an independent prognostic factor.     

Haematological changes and infectious complications in anorexia nervosa: a case-control study

To determine the prevalence of haematological abnormalitiesin patients with anorexia nervosa (AN), and assess the relationshipsbetween these changes, the severity of AN and the propensityto infections, we retrospectively studied 67 patients who metthe DSM-III-R diagnostic criteria for AN. We recorded physicalfindings and routine haematological data on admission, and infectiousevents during hospitalization. The patients were compared with67 normal controls matched for age and sex. Mean haemoglobin(Hb) was normal but lower in AN patients than in controls (131± 1 9 vs. 137 + 11 g/l, p=0.03) and the prevalence ofanaemia (Hb<120 g/l) was higher in the AN group (27% vs.1.5%, p<0.0001). Patients had a lower leucocyte count (4.94+ 1.9 vs. 6.78 + 2.4 x10⁹/ l , p< 0.0001), and increasedprevalence of leucopenia ( < 4 x 10 ⁹ cells/l)(36% vs. 1.5%,p<0.0001), neutropenia (<1500x10⁶ cells/l)(17% vs. 0%,p=0.0015)and thrombocytopenia (<150x109 / l ) (10% vs. 0%, p = 0.03).Only 2 patients (3%) had pancytopenia, but 9/17 patients withanaemia (53%) also had leucopenia. There was a slight but significantcorrelation between body-mass index (BMI) and total leucocyte,neutrophil and red blood cell counts. Severe infectious complicationsoccurred in 9% of AN patients vs. 0% in controls (p = 0.01);they were more frequent with neutropenia (relative risk, 15.1:95% Cl, 10–20.2) or low (<12) BMI (relative risk, 11.6:95% Cl, 6.6–16.6) on admission. Compared with controls,AN patients thus had an increased prevalence of anaemia, leucopeniaand thrombocytopenia. The severity of AN, as assessed by BMI,correlated with leucocyte, neutrophil and red blood cell countsbut not with platelet count The risk for subsequently developingsevere infections was significantly increased when low BMI orneutropenia was found on admission.     

Evidence of oxidant injury and tubular damage in early diabetic nephropathy

Two groups of patients with insulin-dependent diabetes mellitusof >10 years duration and either persistent normoalbuminuria(group 1, n = 49; albumin excretion <30mg/day) or microalbuminuria(group 2, n = 33; albumin excretion 30–300 mg/day) wereinvestigated for evidence of free oxygen radical activity (erythrocyticsuperoxide dismutase and glutathione peroxidase) and oxidantinjury (serum malondialdehyde). Glomerular proteinuria (albu-minuria,transferrinuria), tubular proteinuria (ret-inol-binding protein)and tubular enzymuria (N-acetyl-glucosaminidase and leucineaminopeptidase) were also measured. Healthy controls (n = 38)were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration ofdiabetes and recent glycaemic control. Serum cholesterol andcreatinine were similar in all three groups. Free-radical activityand oxidant injury were significantly higher in groups 1 and2 than in controls (p< 0.001). Glomerular proteinuria, tubularproteinuria and enzymuria were significantly higher in group2 than in group 1 and controls (p<0.01). Group 1 had significantlyhigher transferrinuria, tubular enzymuria and tubular proteinuriathan controls. However, groups 1 and 2 were similar in degreeof free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damageaccompany and may even precede microalbuminuria. The presenceof these abnormalities in the absence of glomerular proteinuriafavours the hypothesis that alterations first occur in the peritubularmicrocirculation, which by causing oxidant injury and tubulardamage, may initiate diabetic nephropathy.     

Progression of Diabetic Autonomic Neuropathy over a Decade in Insulin-Dependent Diabetics

The prognosis for diabetics with autonomic neuropathy is littleknown. We therefore studied the progress of young insulin-dependentdiabetics, first identified as having abnormal autonomic function10–15 years ago. We have shown that the mortality of diabeticswith symptomatic authonomic neuropathy is increased, but isless than previously reported. Mortality in asymptomatic diabeticswith an isolated abnormality in autonomic function tests isnot increased. The heart rate variability declines at 1.02±0.47(SD) per annum in diabetics with an initially normal heart ratevariability. While symptoms of autonomic neuropathy do not usuallyremit even over a decade, they do not commonly progress. Three groups of young insulin-dependent diabetics had heartrate variability tested between 1972 and 1977 and have beenreviewed 10–15 years later. Group A (n=49) had symptomaticautonomic neuropathy and an abnormal heart rate variability(<12), Group B (n=24) were asymptomatic yet had an abnormalheart rate variability and Group C (n=38) were asymptomaticand had a normal heart rate variability (16–26). The 10-yearsurvival in Group A (73.4 per cent) was less (P<0.05) thanin Groups B (91.7 per cent) or C (89.5 per cent) which did notdiffer from each other. The 18 Group A deaths were due predominantlyto renal failure (n=4), myocardial infarction in patients withnephropathy (n=3) and sudden unexpected death (n=3). The chiefsymptoms of autonomic neuropathy-diarrhoea, postural hypotensionand gustatory sweating, were very persistent but did not necessarilydeteriorate or become disabling in the majority of patients.The development of autonomic symptoms in asymptomatic patientswith abnormal heart rate variability was uncommon over a decade.     

Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study

Following a femoral neck fracture and vertebral compressionfractures in two patients with severe haemophilia A, bone densityand turnover were measured in 19 males with severe haemophiliaA (all HIV negative, 18/19 hepatitis C antibody positive) andin 19 age/sex matched controls. Bone density at the lumbar spine(L2–4), measured by dual energy X-ray absorptiometry,was significantly lower in the haemophiliac patients (HPs) at(mean ± SEM) 1.109 ± 0.042 g/cm² vs. 1.234 ±0.027 in controls; p = 0.018. Femoral neck density was alsolower at 0.877 ± 0.034 g/cm² (HPs) vs. 1.067 ±0.032; p< 0.0005. No significant differences were evidentbetween the groups for serum calcium, parathyroid hormone, luteinizinghormone, follicle-stimulating hormone or 1,25 dihydroxyvitaminD3, nor for fasting urinary hydroxyproline, pyridinoline ordeoxy-pyridinoline excretion. Serum total alkaline phos-phatasewas elevated in HPs at 200 ±10 U/l vs. 158 ± 8;p = 0.004. Similarly, -glutamyl transferase was elevated at42 ±7 U/l (HPs) vs. 20 ±2; p = 0.007. Serum totaltestosterone and sex-hormone-binding globulin (SHBG) were higherin HPs at 26 ± 2.5 nmol/l vs. 17.4 ± 1.6 (p =0.009) and 56 ±6 nmol/l vs. 27 ± 3 (p = 0.0005),respectively. Free androgen index, however, was lower in HPsat 44 ± 5 vs 69 ± 7; p = 0.008. These resultssuggest significant osteopenia associated with haemophilia A.This may be partly due to liver dysfunction in HPs, but otherfactors, e.g. relative immobilization, may also be relevant.     

Patterns of Insulin Dependence in an African Diabetic Clinic

SUMMARY Analysis of the age of onset of diabetes amongst insulin-treatedpatients in a large African diabetic clinic revealed a bimodaltype of distribution, 23 per cent having an age of onset before30 years and 77 per cent with onset at 30 years of age. All66 of the young insulin-treated group (21.7±4.8 years(mean±1 SD)), and a random selection of 50 older insulin-treatedpatients (49.7±10 years), were studied. The older groupwere better controlled (HbA₁ 8.4±1.7 per cent vs. 10.8±2.6per cent, p<0.001), on lower doses of insulin (49±23vs. 71±23 u/day, p<0.001) and had higher body massindex (26.0±5.6 vs. 21.8±3.5, p<0.001). SerumC-peptide (0.24±0.15 vs. 0.07±0.10 nmol/l, p<0.0001),and C-peptide/glucose ratio (2.57±2.65 vs. 0.56+0.98nmol/mmolx 10², p<0.001) were very significantly higher inolder patients. Patients with later onset disease thus had betterpreservation of pancreatic function, higher body mass indexand better glycaemic control on lower doses of insulin. Thesefeatures suggest that older insulin-treated patients could infact be ‘Type 2’ or non-insulin dependent patients,and the condition may be controllable with diet and/or oralhypoglycaemic agents, at least in some.     

Comparative Electropharmacological Actions of Some Constituents from Ginkgo biloba Extract in Guinea-pig Ventricular Cardiomyocytes

Effects of the constituents from Ginkgo biloba extract (GBE)on the action potentials and the ionic currents in guinea pigventricular cardiomyocytes were investigated using whole-celland current-clamp techniques. The constituents, ginkgolidesA, B, C and quercetin, had depressant effects at 0.1–3µMon the action potential configuration. Ginkgolide A (1–3µM) prolonged the action potential (action potential duration:APD) at 75% and 90% repolarizations (APD₇₅ and APD₉₀). However,ginkgolides B and C at low concentrations prolonged APD, butat higher concentrations (>1 µM) shortened APD. Quercetinat 3 µM prolonged the APD, but not at the lower concentrations.These constituents also inhibited the V_max. The resting potentialwas unaffected. In voltage-clamp experiments, ginkgolides Aand B (0.1–3 µM) markedly and concentration-dependentlyincreased the Ca²⁺ current (I_Ca) and the delayed rectifier K⁺current (I_K), and decreased the inwardly rectifying K⁺ current(I_K1). On the other hand, ginkgolide C failed to affect theI_Ca but increased the I_K by 14.0 ± 2.3% (n = 6, P <0.05) at 1 µM. Quercetin inhibited I_Ca, and enhanced I_Kbut decreased I_K1. These responses to the constituents werealmost reversible (80–90% of control) after a 10- to 20-minwashout. These results indicate that even at acute administrations,these constituents produce the effective actions on the APDand the underlying ionic currents in cardiomyocytes. Each constituentdoes not exhibit a uniform response, although GBE acts as anet.     

Abnormal Platelet Function and Ultrastructure in Fulminant Hepatic Failure

Evidence in favour of an acquired platelet defect in fulminanthepatic failure has been provided by studies of in vitro plateletaggregation with adenosine diphosphate (ADP). Platelets fromsix patients required a higher concentration (threshold concentration)of ADP to reach second phase aggregation than those from controls(12·3 compared with 2·2x10^–6 M). Plateletsfrom another six patients failed to show second phase aggregationat the highest concentration of ADP used (3·2x10^–6M). The degree of aggregation at a fixed concentration (3·2x^–6M) was significantly less than in controls (34·2 percent compared with 57·5 per cent). Capillary bleedingtimes correlated positively with the abnormalities of plateletaggregation. In crossover studies, platelet poor plasma fromthese patients did not inhibit platelet aggregation in controls,nor did platelet poor plasma from controls enable patients'platelets to reach second phase aggregation suggesting thatfactors other than the plasma were responsible for this abnormalplatelet function. Some relationship between the severity of hepatic necrosis andplatelet dysfunction can be deduced as platelet function wasnormal in 16 patients with virus hepatitis or liver damage followingparacetamol overdose who were ill enough to warrant hospitaladmission, but who did not develop fulminant hepatic failure. Electron microscopy of platelets from patients with fulminanthepatic failure showed many structural abnormalities includingnumerous pseudopods, vacuoles and blurred plasma membranes.Most striking were the numbers of platelets showing microtubules,and the increased microtubular content per platelet. As patientsrecovered from fulminant hepatic failure, platelet functionimproved and platelets with normal ultrastructure appeared amongstthe abnormal ones. The abnormal-looking platelets may be responsible for the abnormalitiesof platelet function, but kinetic studies are required to elucidatetheir source and fate.     

Improvements in glycaemic control and cardiovascular risk factors in a cohort of patients with type 1 diabetes over a 5-year period

Background: Management of patients with type 1 diabetes in theUK has changed over the past 20 years. The targets for glycaemiccontrol, blood pressure and cholesterol are lower. We examineda cohort of patients with type 1 diabetes who have been throughthese changes to assess their effects. Design and Methods: A cohort of patients with type 1 diabeteswho attended a secondary care outpatient diabetes clinic between1991 and 1996 were reviewed in 2001and 2006. Comparison is madebetween current biophysical markers and those obtained in 2001. Results: Only 81.9% (n = 214) of the original cohort attendedin 2006. These patients had an average duration of diabetesof 23.46 (SD ± 8.06) years. There were 134 male patients(62.62%). In these patients HbA1c had reduced by 0.4% (absolutereduction); a relative reduction of 4.41% (P = 0.0001). Statisticallysignificant reductions in diastolic blood pressure (74–68mmHg) and total cholesterol (5.37–4.62 mmol/l) occurred.However, weight (75.04–82.31 kg) and BMI (25.32–27.72kg/m²) significantly increased. There was no statistically significantchange in insulin dose (units/kg), serum creatinine, urinaryACR or systolic blood pressure. Conclusions: An urban setting, mobile population and patientnon-attendance can complicate modern diabetes care. Despitethese difficulties, input by the diabetes team working withthe patients can achieve small improvements in Hba1c and cardiovascularrisk factors by increased use of long acing insulins, metformin,statins and blood pressure medication.     

Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a multi-centre trial

Thirty-one patients with visceral leishmaniasis (VL) causedby Leishmania infantum received liposomal amphotericin B (AmBisome)in a multi-centre study. Ten immunocompetent patients (six children)received 1–1.38 mg/kg/day for 21 days, and ten (nine children)received 3 mg/kg/day for 10 days. All were cured without significantadverse events and without relapse during 12–24 monthsof follow-up. Eleven immunocompromised adults, including sevenco-infected with HIV (four with AIDS) received 100mg (1.38–1.85mg/kg) daily for 21 days. All were initially considered cured,but eight relapsed clinically and parasitologically at 3–22months. Liposomal amphotericin B is a new, safe and effectivedrug for the treatment of VL.     

Efficacy and tolerability of eperisone and baclofen in spastic palsy: a double-blind randomized trial

Introduction  Few trials have compared different central muscle relaxants in the treatment of spastic palsy. This head-to-head phase 3 trial compares oral eperisone, a central muscle relaxant with a promising activity in spasticity therapy, and oral baclofen. Methods  Patients (>18 years) with moderate to severe spastic palsy were eligible in this double-blind, randomized study; they received eperisone 300 mg/ day or baclofen 60 mg/day for 6 weeks. The efficacy evaluations included: functional analysis (Pedersen’s scale, muscular tone, joint range of motion, 10-meter walking time); physiological and pathological reflexes; and electromyography (Hmax/Mmax amplitude ratio and the Wartenberg test). Physicians and patients globally assessed treatment efficacy. Results  Both eperisone (n=40) and baclofen (n=40) significantly improved functionality of lower limbs versus baseline (eperisone: −9.1%, P<0.01; baclofen: −8.3%, P<0.05), but only eperisone improved this parameter in the upper limbs (−7.8%, P<0.01 vs. −6.3%, P=NS). Both drugs reduced muscular tone from week 2. Only eperisone improved the joint range of motion (−32.5%, P<0.01 vs. −14.6%, P=NS). Both treatments reduced the 10-meter walking time (eperisone: −20.2%, P<0.01; baclofen: −24.0%, P<0.01); this effect was evident at week 2 with eperisone only. Both drugs improved reflexes. Eperisone and baclofen decreased the Hmax/Mmax amplitude ratio (eperisone: −30.0%, baclofen: −18.6%; P<0.01 for both). Eperisone increased the number of leg oscillations at the Wartenberg test (P<0.05) while baclofen increased the velocity of leg falling (P<0.01). For tolerability, no differences were observed between eperisone and baclofen in any parameters. Eperisone was judged as “good“ by a higher number of physicians and patients than baclofen. Eighteen adverse events, most of mild intensity, were reported with eperisone and 27 with baclofen. Conclusion  Eperisone 300 mg/day and baclofen 60 mg/day, administered orally, are effective and well-tolerated drugs in the treatment of spastic palsy. However, eperisone might be associated with some additional clinical benefits when compared with baclofen.     

Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid Overactivity and are at Increased Risk of Developing Overt Hyperthyroidism

The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (4–12)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism.     

Immunological and Psychological Benefits of Aromatherapy Massage

This preliminary investigation compares peripheral blood cellcounts including red blood cells (RBCs), white blood cells (WBCs),neutrophils, peripheral blood lymphocytes (PBLs), CD4⁺, CD8⁺and CD16⁺ lymphocytes, CD4⁺/CD8⁺ ratio, hematocrit, humoralparameters including serum interferon- and interleukin-6, salivarysecretory immunoglobulin A (IgA). Psychological measures includingthe State–Trait Anxiety Inventory (STAI) questionnaireand the Self-rating Depression Scale (SDS) between recipients(n = 11) of carrier oil massage and aromatherapy massage, whichincludes sweet almond oil, lavender oil, cypress oil and sweetmarjoram oil. Though both STAI and SDS showed a significantreduction (P < 0.01) after treatment with aromatherapy andcarrier massage, no difference between the aromatherapy andcontrol massage was observed for STAI and SDS. Aromatherapy,in contrast to control massage, did not significantly reduceRBC count or hematocrit. However, aromatherapy massage showeda significant (P > 0.05) increase in PBLs, possibly due toan increase in CD8⁺ and CD16⁺ lymphocytes, which had significantlyincreased post-treatment (P < 0.01). Consequently, the CD4⁺/CD8⁺ratio decreased significantly (P < 0.01). The paucity ofsuch differences after carrier oil massage suggests that aromatherapymassage could be beneficial in disease states that require augmentationof CD8⁺ lymphocytes. While this study identifies the immunologicalbenefits of aromatherapy massage, there is a need to validatethe findings prospectively in a larger cohort of patients.     

Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension

In a double-blind, double-dummy, randomized, multi-centre study,the effects of bendroflumethiazide vs. enalapril on blood pressure,glycaemic control, lipoprotein concentrations and albuminuriawere compared in non-proteinuric, hypertensive type 2 diabeticpatients; they were treated for 20 weeks with either bendroflumethiazide2.5–5.0 mg (n=59) or enalapril 10–20 mg (n=55).Age, fasting plasma glucose, HbA_1c and BMI were similar in thegroups. Systolic and diastolic blood pressure were reduced inboth groups. Bendroflumethiazide was accompanied by minor butsignificant elevations in fasting plasma glucose and serum C-peptide.HbAic was increased during both treatments. Lipoproteins andurinary albumin/creatinine ratio were stable. Bendroflumethiazidecaused a decrease in serum potassium and an increase in serumurate. No significant correlations were observed between thedecline in blood pressure and changes in the metabolic riskfactors. Baseline levels of age, sex, BMI, blood pressure orurinary albumin/creatinine ratio were not related to changesin blood pressure, metabolic parameters or urinary albumin/creatinineratio.     

Prevalence of chronic kidney disease stages 3-5 among acute medical admissions: another opportunity for screening

Background: Early identification of chronic kidney disease (CKD)can help delay or prevent its progression, but the opportunitiesfor systematic screening of patients are not well defined. Aim: To define the prevalence of CKD Stages 3–5 and relatedanaemia among acute medical admissions. Design: Retrospective analysis. Methods: We studied all acute medical admissions to a majorLondon teaching hospital during one year. The lowest creatinine,highest haemoglobin (Hb) and average mean corpuscular volume(MCV) were determined for 3 months before and after admission.Patients were categorized as CKD Stages 3–5 if the highestestimated GFR (eGFR) was <60 ml/min/1.73 m². CKD-relatedanaemia was diagnosed if these patients had Hb <11 g/dl withnormal MCV. Results: A total of 6073 patients were studied: male 49.0%,age 65.4 ± 19.6 years (mean ± SD), creatinine82.7 ± 46.7 µmol/l, eGFR 89.1 ± 32.5 ml/min/1.73m², Hb 13.6 ± 1.73 g/dl, MCV 87.7 ± 7.2 fl. Therewas an inverse correlation between eGFR and age (r² = 0.5; P< 0.001). Males were younger than females (63.5 ±18.4 years vs. 67.3 ± 20.5) and had higher eGFR (93.6± 34.1 vs. 84.7 ± 30.2 ml/min/1.73 m²; P <0.001). A total of 743 patients (12.2%) had raised creatinine>110 µmol/l, however using eGFR <60 ml/min/1.73m², 1075 patients (17.7%) were identified. The patients werecategorized as follows: Stage 3: 950 (15.6%), Stage 4: 100 (1.7%),Stage 5: 25 (0.4%). Ninety-nine (9.2%) of the 1075 patientshad normocytic anaemia. Conclusions: We have found a high prevalence of CKD Stages 3–5(17.7%) among acute medical admissions, of whom 9.2% had a relatedanaemia. Our findings highlight an important opportunity (amongstthe 1.9 million acute medical admissions annually in England)for detecting patients with CKD.