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.     

Abnormalities of Glucose Tolerance Following Gestational Diabetes

Glucose tolerance and insulin secretion were studied in 56 women6–12 years following a pregnancy complicated by gestationaldiabetes, and in 23 matched controls. At recall 14 women wereknown to have diabetes and five were again pregnant with recurrentgestational diabetes. The early development of diabetes wasassociated with a fasting plasma glucose >6 mmol/l duringpregnancy and with a high plasma glucose response to oral glucosewhich persisted after delivery. Obesity was predictive of non-insulin-dependentdiabetes whereas those that later required insulin were notobese. At recall, seven of the remaining 37 women were foundto have unrecognized diabetes, 13 had impaired glucose tolerance(IGT) and 17 were normal by WHO criteria using a 75 g oral glucosetolerance test. In these 37 women, fasting plasma glucose andthe glucose response to oral glucose in pregnancy were not predictiveof subsequent diabetes or impaired glucose tolerance. Obesityin pregnancy and subsequent weight gain were associated withnon-insulin-dependent diabetes and impaired glucose toleranceat recall. Insulin deficiency was observed during the oral glucosetolerance test in the diabeties (the mean±SEM ratio insulinarea: glucose area 4.1±1.3 diabetics, 10.7±1.8controls, p<0.05), whereas in the group with impaired glucosetolerance insulin levels were high and in proportion to theirhyperglycaemia (insulin area: glucose area 10.9±1.4 1GT,9.4±1.4 controls). Women with normal glucose toleranceand previous gestational diabetes had significantly lower insulinresponses than their controls, despite mild hyperglycaemia (insulinarea: glucose area 4.0±0.7 normal glucose tolerance,7.6±1.1 controls, p<0.02). Abnormalities of glucosetolerance and insulin secretion are present following a gestationaldiabetic pregnancy. Gestational diabetes identifies women atrisk for developing diabetes and impaired glucose tolerance,both of which are risk factors for premature vascular disease.     

Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion capacity

The mixed expired nitric oxide (NO) production of the lungsof patients with primary pulmonary hypertension (PPH) and normalsubjects was measured to determine the relationship betweenNO production and the diffusion capacity of the lung (KCO).Expired air was collected from eight patients with PPH and 20healthy volunteers for analysis by a chemluminescent analyser.Mean pulmonary artery pressure in the PPH patients was 59.5± 6.45 mmHg and their mean cardiac output was 2.95 ±0.35 l/min. All patients and subjects underwent measurementsof FEV1, VC and KCO. The rate of production of NO in mixed exhaledair was lower in the PPH group compared to the controls (2.85± 0.7 vs. 4.69 ± 0.35 nM/min; p<0.05). Therewas a good correlation of expired NO with the KCO (r=0.7; n=30;p<0.001). When corrected, KCO differences in exhaled NO werenot significant (p=0.09). We conclude that the low exhaled NOobserved in PPH patients is a reflection of the reduced bloodcapillary volume in these patients rather than a decreased basalproduction of NO.     

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.     

A Comparative Study of the Relative Effects of Anticonvulsant Drugs and Dietary Folate on the Red Cell Folate Status of Patients with Epilepsy

In a survey of the red cell folate status of 200 patients withepilepsy, compared to 72 controls, we found that median redcell folate levels were reduced significantly in patients treatedwith phenytoin (p<0.01) or carbamazepine (p<0.001) alone.Patients taking more than one drug had reduced levels also (p<0.001),but in patients treated with sodium valproate alone there wasno significant decrease in red cell folate levels compared tocontrols. Twenty-two per cent of patients in the group takingmore than one drug had reduced levels of red cell folate comparedwith 17 per cent of those taking carbamazepine alone, 13 percent of those taking phenytoin only, and 9 per cent of thosetaking sodium valproate only. Dietary folate intake was significantlyreduced in all the patient groups compared with controls (p<0.001for the carbamazepine and phenytoin groups, p<0.01 for thepolypharmacy and sodium valproate groups); a significant correlation,between red cell folate levels and dietary folate was not established. Significant negative relationships were established betweencarbamazepine dose (r=0.35, p<0.01) or serum level (r=-0.27,p<0.05) and red cell folate level in patients on one drugonly. The correlation between dose or serum level-of phenytoinand red cell folate level was also negative but did not reachsignificance. Our findings show that all anticonvulsant drugs interfere withfolate metabolism. While the effect is greatest with drugs whichinduce microsomal liver enzymes, low levels of folate also occurredin patients taking the non-enzyme inducer sodium valproate.Although a significant relationship between diet and red cellfolate was not established, dietary folate could be a furthercontributory factor.     

Urinary Catecholamines in Essential Hypertension: Results of 24-hour Urine Catecholamine Analyses from Patients in the Medical Research Council Trial for Mild Hypertension and from Matched Controls

Four consecutive 24-h urine samples were collected from 134male and 134 female placebo-treated patients in the MedicalResearch Council Trial for Mild Hypertension. Similar sampleswere collected from age and sex-matched normotensive controls.On the fourth day noradrena-line excretion was 22.05 ±1.01 nmol/mmol creatinine in the hypertensives compared with22.22 ± 1.16 nmol/mmol creatinine in the controls. Adrenalineexcretion on the same day was 6.13 ± 0.33 nmol/mmol creatininein the hypertensive subjects compared with 6.32 ± 0.38nmol/mmol creatinine in the controls. There was no significantdifference for either catecholamine between the two groups.However, in the control group there was a highly significantcorrelation between excretion of adrenaline and systolic bloodpressure (r = 0.218, p = 0.0004) and between noradrenaline excretionand systolic blood pressure (r = 0.200, p = 0.001). Catecholamineexcretion and blood pressure were not significantly correlatedin the hypertensive patients. There were no significant correlationsin either group between catecholamine excretion and heart rate,caffeine intake, nicotine consumption or the Bortner self-assessmentscore of personality type. This study has found no evidenceof elevated sympathoadrenal activity in mild hypertensives.The correlations in the control group may reflect the role ofsympathoadrenal activity in acute fluctuations in blood pressureor may suggest that the level of blood pressure within the ‘normal’range depends in part on the level of sympathoadrenal activity.     

Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity?

Background  Obesity is a well-known problem in children with acute lymphoblastic leukemia (ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with intermittent dexamethasone (DEXA). Methods  Body mass index (BMI), energy intake, and physical activity were measured in 16 ALL patients on maintenance treatment and in 17 healthy controls. ALL patients were measured during (“on DEXA”) and in between (“off DEXA”) DEXA treatments. Results  In patients, the mean increase in BMI z-score was 1.4 ± 1.1. Energy intake on DEXA was higher (2,125.9 ± 476.0 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05) and energy intake off DEXA was lower (1,305.0 ± 249.4 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05), compared to healthy controls. Physical activity on DEXA was lower compared to healthy controls (30.0 ± 3.9 vs 40.0 ± 6.0 kcal kg⁻¹ 24 h⁻¹, p < 0.001 and 7,303.1 ± 4,622.9 vs 13,927.2 ± 3,822.7 steps, p < 0.05). Physical activity off DEXA was not different compared to healthy controls. Conclusion  Weight gain in patients on ALL treatment might be owing to increased energy intake and decreased physical activity during treatment with DEXA.     

Thrombin and Plasmin Activity in Diabetes Mellitus and their Association with Glycaemic Control

Abnormalities of haemostasis are common in diabetes mellitus.As indicators of fibrinolysis and coagulation, plasmin and thrombinactivity were assessed by assay of the fibrinogen peptide derivativesBß_15-42 and fibrinopeptide A respectively in 60 diabeticpatients and 50 control subjects in a cross-sectional study.Glycosylated haemoglobin (HbA₁) correlated with Bß_15-42(r=0.26, p<0.05) and fibrinopeptide A (r=0.30, p<0.05)in the diabetic patients suggesting that poor glycaemic control(i.e high HbA₁ levels) was associated with depressed plasminand enhanced thrombin activity. Compared to controls, fibrinopeptideA levels were increased in diabetics (p<) irrespective ofsex or type of diabetes. Bß_15-42 levels were normalin diabetic females but increased in diabetic men (p<0.001)possibly secondary to the activation of coagulation. These resultssuggest that in diabetes mellitus activation of coagulationis the dominant haemostatic abnormality and that better glycaemiccontrol could influence in-vivo plasmin and thrombin activityfavourably.     

Metabolic Studies in Kidney Stone Disease

Patients with kidney stones (n=59) and healthy controls (n=31)collected a 24-hour urine sample and later underwent a 6-hour‘fast and load’ test in which an oral calcium loadwas taken after 2 hours. In the 24-hour urine sample, mean calciumexcretion was higher in patients than controls, while mean urate,oxalate and citrate levels were similar. The patients had higherlevels of fasting plasma calcium, serum calcitriol and fastingurinary calcium, and lower levels of plasma phosphate than didthe controls. Following the calcium load, plasma and urinarycalcium increased similarly in both groups. Serum parathyroidhormone (PTH) levels were similar in both groups and decreasedsimilarly following the calcium load. Multiple linear regression, relating the presence or absenceof stone formation to all variable, found the only variablessignificantly related to stone formation to be plasma levelsof calcium (p<0.001) and phosphate (p=0.001) and fastingurinary area (p<0.001), and 24-hour urinary calcium excretion(p<0.05). Urinary oxalate and citrate were not related tostone formation. The data do not support the hypothesis thatprimary stimulation by calcitriol produces a normal fastingplasma calcium level, with an exaggerated increase after anoral calcium load. The findings instead suggest an abnormalityof parathyroid cell ‘set point’, such that PTH secretioncontinues until the plasma calcium level is a little higherand the phosphate a little lower than in controls.     

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.     

Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic D-glucose in euglycaemic clamped diabetic patients and healthy controls. 2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 +/- 1.0 to 304.1 +/- 1.6 mosmol/kg, mean +/- SEM, P less than 0.001) and controls (288.6 +/- 0.9 to 305.7 +/- 0.6 mosmol/kg, P less than 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 +/- 0.3 to 7.7 +/- 1.5 pmol/l, P less than 0.001; controls 0.5 +/- 0.1 to 6.5 +/- 1.0 pmol/l, P less than 0.001) and thirst ratings (diabetic patients 1.0 +/- 0.2 to 7.1 +/- 0.5 cm, P less than 0.001; controls 1.8 +/- 0.4 to 8.0 +/- 0.5 cm, P less than 0.001) in both groups. 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls. 4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = +0.89, controls r = +0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion. 5. Hypertonic D-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 +/- 0.2 to 20.1 +/- 1.2 mmol/l, P less than 0.001) and healthy controls (4.3 +/- 0.1 to 19.3 +/- 1.2 mmol/l, P less than 0.001) but did not change plasma vasopressin or thirst ratings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Androgenic Status and Sexual Function in Males with Rheumatoid Arthritis and Ankylosing Spondylitis

The pituitary-testicular axis was investigated in 31 males withrheumatoid arthritis (age range 19–60 years, median 55years) and 33 males with ankylosing spondylitis (age range 22–55years, median 37 years) and compared with a control group of95 normal male volunteers. Using analysis of covariance, patientswith rheumatoid arthritis showed significantly lower serum testosterone(p<0.05) and derived free testosterone (p<0.01) concentrationsand significantly higher serum LH and FSH concentrations (p<0.05)compared with controls. All patients had normal serum prolactinand cortisol concentrations. Serum testosterone correlated withESR, haemoglobln concentrations and rheumatoid factor titres(r<–0.448, p<0.02; r=0.440, p<0.02; r<–0.360,p<0.05 respectively) in the rheumatoid patients. Althoughthere was a significant negative correlation between ESR andhaemoglobin concentrations (p<0.005) in the patients withankylosing spondylitis, neither variable correlated with serumtestosterone concentrations. There was no association betweentesticular dysfunction and the presence of extraarticular featuresof rheumatoid arthritis. Ten patients (33 per cent) with rheumatoidarthritis and four (13 per cent) with ankylosing spondylitisadmitted to periods of impotence while 15 (50 per cent) of theformer and 12 (39 per cent) of the latter had periods of decreasedlibido. There was no evidence for increased rates of infertilityin either group.     

Lipoprotein(a) as a determinant of the severity of angiographically defined carotid atherosclerosis

We measured fasting serum lipids, lipoproteins, apolipoproteinsand lipoprotein(a) [Lp(a)] in 49 Caucasian patients with transientischaemic attacks undergoing carotid angiography. The severityof extracranial cerebrovascular disease was assessed visuallyby a highly reproducible grading system that focused on theinternal carotid artery and carotid bifurcation. Compared witha healthy reference group, patients had significantly higherserum concentrations of: total cholesterol (mean ± SD),6.2 ± 1.6 vs. 5.6 + 1.0 mmol/l, p = 0.02; apolipoproteinB, 1.4 ±0.5 vs. 1.2±0.3g/l, p = 0.03; triglyceride[geometric mean(95% Cl)], 2.02(1.75–2.32) vs. 1.66(0.67–4.06)mmol/l, p = 0.03; and Lp(a), 0.33(0.26–0.42) vs. 0.17(0.40–0.76)g/l, p <0.001. Regression analysis showed that of the lipoprotein-relatedvariables, only Lp(a) was significantly related to the severityof carotid artery disease (p = 0.04) in the patients; this associationremained significant after adjusting for age, sex, blood pressure,and a history of stroke. Serum Lp(a) concentration was significantlyhigher in patients with carotid artery disease severity scoreabove the median value of the sample population compared withthose below the median: 0.45 vs. 0.24 g/l (95% Cl for difference0.35–0.88), p = 0.01. Elevated serum Lp(a) is a significantdeterminant of the extent of carotid atherosclerosis and maybe useful in identifying patients most at risk of stroke.     

Endocrine crises. Diabetes insipidus

Normal water balance with strict maintenance of plasma osmolality depends on appropriate water conservation (controlled by ADH release and action) and additional water intake if required (triggered by the awareness of thirst). Central nervous system pathology (including trauma) commonly involves the hypothalamus and pituitary stalk, leading to impaired osmoreceptor function or diminished ADH production or release, resulting in diabetes insipidus (with potentially life-threatening abnormalities in fluid and electrolyte status). Assessment of the relationships between plasma and urine osmolality and plasma ADH levels will usually lead to an accurate diagnosis. Central diabetes insipidus is effectively treated with replacement of free water deficits and exogenous ADH analogues.     

Mean platelet volume in diabetes mellitus

We measured mean platelet volume (MPV) in patients with diabetesmellitus, compared with MPV in non-diabetic control subjects.Mean MPV was significantly increased in the diabetic subjects(8.9 ± 0.07 fL, mean ± SEM) compared with nondiabeticsubjects (8.0 ± 0.05) (p < 0.001). Since plateletsize is a determinant of platelet function, with larger plateletsbeing more reactive per unit volume, we believe platelets mayplay a part in the micro- and macro-vascular complications ofdiabetes mellitus.     

Mean platelet volume in diabetes mellitus

We measured mean platelet volume (MPV) in patients with diabetesmellitus, compared with MPV in non-diabetic control subjects.Mean MPV was significantly increased in the diabetic subjects(8.9 ± 0.07 fL, mean ± SEM) compared with nondiabeticsubjects (8.0 ± 0.05) (p < 0.001). Since plateletsize is a determinant of platelet function, with larger plateletsbeing more reactive per unit volume, we believe platelets mayplay a part in the micro- and macro-vascular complications ofdiabetes mellitus.     

Haemostatic Changes in the Loin Pain and Haematuria Syndrome: Secondary to Renal Vasospasm?

Twenty-five patients (seven male, 18 female) were diagnosedas having the loin pain and haematuria syndrome. Presentingsymptoms were either loin pain alone or pain associated withmacroscopic or microscopic haematuria, and were longstanding,having been present for mean of 9.3 years in males, and 10 yearsin females. Ten patients described symptoms of passing gravelor renal stones but these were only demonstrated radiologicallyin two patients. Investigation of all patients showed anatomicallynormal renal tracts, normal renal function, and no significantproteinuria. Phase-contrast microscopy during episodes of haematuriarevealed dysmorphic red cells in all 10 patients studied. Renalbiopsies were performed in 20 patients and showed no glomerularpathology, but arteriolar and arterial hyalinosis was seen in13 of 20 (65 per cent), fibro-elastosis in larger vessels ineight of 20 (40 per cent) and red blood cells in tubules in13 of 20 (65 per cent) patients. The histological appearancein vessels was similar to that seen in cyclosporin A nephrotoxicityand would be consistent with the hypothesis that regional vasospasmoccurs in the cortical circulation. Haematological studies in22 patients, when compared with age and sex matched controls,showed the presence of circulating platelet aggregates, elevationof plasma ß-thromboglobulin (p < 0.001), and increasedplatelet aggregation in response to serotonin and ADP (p <0.05 and p < 0.03, respectively). Plasma concentrations ofD dimer (p < 0.02) and C-reactive protein (p < 0.03) werealso significantly elevated in the patient group. There wasno deterioration of renal function during a mean observationperiod of 3.7 years and no patients developed proteinuria. Treatmentwas largely supportive; seven patients with intractable loinpain underwent surgical denervation with the relief of painin four.     

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.     

Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP–1) and its inhibitor (TIMP–1) in DCM patients

Summary Left ventricular dilation and myocardial remodeling are hallmarks of dilated cardiomyopathy (DCM). It is assumed that left ventricular dilation is caused by the disintegration of the collagenous network by increased collagenolytic activity of matrix metalloproteinases (MMPs) and their adequate tissue inhibitors (TIMPs). In this study the myocardial MMP–1 and TIMP–1 mRNA expressions were investigated by using real–time quantitative PCR analysis from right septal endomyocardial biopsies of patients with dilated cardiomyopathy (n = 46) and control subjects (n = 11). The volume density (Vv%) of collagen was measured morphometrically. Classification was done according to LV diameters [left ventricular enddiastolic diameter (LVEDD, cm) calculated to body surface area (BSA, m²)] into three DCM groups: group I (LVEDD–BSA > 2.7–3.0 cm/m²), group II ( > 3.0–3.6 cm/m²), group III ( > 3.6 cm/m²), controls (< 2.7 cm/m²). Compared with controls, the MMP–1 expression in patients with DCM was significantly increased (119.2 ± 45.2 vs. 1.3 ± 0.4; p < 0.001) as was TIMP–1 expression (9.6 ± 1.2 vs. 1.3 ± 0.4; p < 0.01). Moreover the MMP–1 and TIMP–1 expression varied according to LV diameter: group I (MMP–1: 8.7 ± 3.5; p = 0.33; TIMP– 1: 4.5 ± 1.2; p < 0.01); group II (MMP–1: 211.4 ± 86.0; p < 0.001; TIMP–1: 12.5 ± 1.9 ; p < 0.001); group III (MMP–1: 38.8 ± 22.6; p < 0.01; TIMP–1: 8.1 ± 1.7; p < 0.001). Compared with controls, the collagen level in DCMPt. was significantly increased: 5.0 ± 0.6 vol% vs 1.2 ± 0.2 vol% p < 0.001 and correlates with LV diameter. This study reveals that the overexpression of MMP–1, which is associated with an increased ratio of MMP–1/TIMP–1 in DCM, indicates an activated collagenolytic system while replacement fibrosis is accumulating. The MMP–1 overexpression is mainly found in moderately dilated DCM hearts (group II) indicating the dynamic process of LV dilation and the importance of collagenases in the early phase of LV remodeling.     

Malaria prophylaxis: identifying risk groups for non-compliance

To investigate behaviour in the use of drug prophylaxis againstmalaria and the risk factors for noncompliance, 507 Europeanor North American travellers returning from endemic areas werestudied retrospectively at Berlin in a 11-year periad from 1980to 1990. Compliance was significantly correlated with shortertravel duration: the group with good compliance stayed 37.2±38.5days (mean±SD) in contrast to 69.8±93.5 days inthe group of patients with no compliance (p = 0.00001). Olderpatients were significantly more compliant than patients aged<55 years (20/27 compliant at >54 years vs. 175/476 at< 55 years; p = 0.0001 ). Compliance was significantly affectedby travel destination (Southern and East African regions; p= 0.0054), age (< 15 and < 55 years, respectively; p =0.0001), and reason of travel (package tours; p = 0.0001). CARTanalysis confirmed logistic regression analysis with respectto age and travel type, and revealed that patients using onlyone information source were significantly more compliant thanthose using two or more information sources. Travel agencieswere nearly as well informed as Institutes of Tropical Medicine,but family doctors had a significant incidence of giving wrongadvice. This study should enable medical personnel dealing withprophylactic advice against malaria to identify patients athigh risk for noncompliance, and to educate them more carefullythan other travellers regarding antimalarial drug prophylaxis.