Prolactin dynamics and tumour size in the prediction of surgical outcome for prolactinoma

Each of 62 females were studied for a period of between two and 72 months (mean 36 months) following the removal of a prolactinoma by transsphenoidal pituitary surgery. Our aims were to define the relationships between pre- and post-operative features, the operative findings and the functional outcome. Pre-operative serum prolactin (PRL) concentrations correlated with tumour diameter (r = 0.55, p less than 0.001). Following surgery two groups of patients were identified: Group 1, 46 spontaneously and regularly menstruating patients and Group 2, 16 patients with persistent amenorrhoea. The patients in Group 1 had significantly lower pre-operative and post-operative serum (PRL) concentrations (p less than 0.02 and p less than 0.001 respectively) and significantly greater PRL responses to thyrotrophin releasing hormone (TRH) and metoclopramide stimulation after surgery (p less than 0.001). There was not a significant difference in tumour size between the groups. Forty-four (96 per cent) of the patients in Group 1 had normal post-operative serum PRL concentrations within one week of surgery. By comparison (p less than 0.001) only 42 and 20 per cent respectively of Group 1 patients who were tested had normal TRH and metoclopramide evoked PRL secretion following surgery. Return of regular menstruation was associated with cessation of galactorrhoea in 44 patients (96 per cent) and ovulation occurred in 37 of 38 menstruating patients for whom data are available. All patients with normal TRH and metoclopramide stimulation tests menstruated spontaneously. Nevertheless most patients who menstruated did so in spite of retaining suppressed PRL responses. Of 46 patients followed to date whose serum PRL was normal one week after surgery, seven later were found to have an elevation of serum PRL outside the normal range but in only two has this been persistent. We suggest that a single measurement of serum PRL one week following transsphenoidal pituitary surgery for prolactinoma provides a good basis for deciding about the future management of patients who desire menstruation and pregnancy.     

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.     

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.     

Clinico-pathological Correlations and Long-term Follow-up of 253 United Kingdom Patients with IgA Nephropathy. A report from the MRC Glomerulonephritis Registry

The Medical Research Council's Glomerulonephritis Registry wasused to study clinicopathological correlations and renal survivalin patients with IgA nephropathy reported between 1978 and 1985.IgA nephropathy was the histological diagnosis in 9.3 per centof all renal biopsies reported to the registry during this period,and in 18.1 per cent of those with a primary glomerulonephritis.The 10-year cumulative renal survival rate accounting for censoreddata (Kaplan-Meier) was 83.3 per cent. Univariate analysis ofsurvival curves (log-rank test) found the following parametersto be significantly correlated with poor renal survival: serumcreatinine >120 µmol/l (p<0.001), hypertension(p<0.001), serum albumin <40 g/l (p<0.005), proteinuria>1 g (p<0.025), age >30 years (p<0.025), and focalmesangial proliferation (p<0.05). There was no significantdifference in renal survival between males and females. Multivariateanalysis (Cox's proportional hazards model) revealed that onlya serum creatinine of > 120 µmol/l and a serum albuminof <40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experienceof IgA nephropathy and the published European experience. IgAnephropathy is not a benign condition in the UK and patientswith impaired renal function and/or those with a reduced serumalbumin are significiantly more likely to progress to end-stagerenal failure within 10 years.     

A prospective study of serum lipoproteins after coronary artery bypass surgery

We examined the acute and long-term effects of coronary arterybypass (CABG) surgery on serum lipid, lipoprotein and apolipoproteinlevels. One series of 34 patients having CABG surgery was studiedpre-operatively and for six weeks afterwards, and another 22patients were investigated before and two years after CABG surgery.None of the patients studied received any lipid-lowering drugtherapy or specific dietary advice. In both groups, pre-operativeserum lipoprotein (a) (Lp(a)) and serum triglyceride concentrationswere raised and serum high-density lipoprotein (HDL) cholesteroland apolipoprotein Al (apo Al) were low compared to healthypeople. Acutely, there were profound decreases of 40–60%in the serum levels of cholesterol (p<0.001), low-densitylipoprotein cholesterol (p<0.05), triglycerides (p<0.01),Lp(a) (p<0.05) and apolipoprotein B (apo B) (p<0.05).There was a small decrease in serum apo A1 (p<0.05), andserum HDL cholesterol showed no change. All these variablesregained their pre-operative values within six weeks. Two yearspostoperatively, serum Lpa was 40% less than its pre-operativeconcentration (p < 0.001) and HDL cholesterol had increased(p< 0.001 ). Triglyceride levels decreased (p<0.02) whenß-blockade was withdrawn. The long-term decrease inLp(a) following surgery is unlikely to be due either to stoppingbeta-blockers or to life-style changes. Myocardial ischaemiarelieved by the operation may have been partially responsiblefor its previously raised concentration.     

Age and Other Determinants of Survival After In-hospital Cardiopulmonary Resuscitation

A retrospective review of 274 patients who received in-hospitalcardiopulmonary resuscitation was performed to determine whetherage is independently associated with survival to discharge.Eighty-two (29.9 per cent) of the 274 patients were resuscitatedinitially, but only 25 (9.1 per cent) were discharged alive.Survival to discharge was significantly poorer in patients aged70 years (6/175; 3.4 per cent) than in patients <70 yearsold (19/99; 19.2 per cent) (p<0.001). Severity of illness,assessed by the number of diagnoses and a multifactorial morbidityindex, did not differ between the two age groups. The best resultswere obtained with witnessed arrests, ventricular arrythmiasand resuscitation lasting less than 5 minutes; however, elderlypatients were less likely to be resuscitated in all circumstances.Age (r=–0.31, p<0.001) and the morbidity index r=–0.18,p<0.05) were independently associated with survival by multivariateanalysis. These results indicate that advanced age is an important independentdeterminant of survival after resuscitation. This should betaken into consideration when making in-hospital resuscitationdecisions.     

A Study to Assess the Efficacy of Chemoprophylaxis in the Prevention of Endoscopy-related Bacteraemia in Patients Aged 60 and Over

Five hundred and fifteen patients aged 60 and over (mean age74.7; 278 men and 237 women) underwent routine endoscopic procedures(gastroscopy, bronchoscopy and cystoscopy). Alternate patientswere given antibiotics before the procedure, as currently recommended,and blood was taken for culture from all patients within fiveminutes of completion of the procedure. Of 74 patients who underwent bronchoscopy, only one culture,from one of 37 controls was positive. Of 262 who underwent gastroscopy,cultures were negative in the 130 who received antibiotics butpositive in 13 of the 132 controls (9.8 per cent p<0.001).Cystoscopy was performed in 179; one culture was positive inthe 88 given antibiotics (1.1 per cent) compared to 25 in the91 controls (27.5 per cent; p<0.001). Bacteraemia rates appear to be low following bronchoscopy (<5per cent) but higher with gastroscopy (10 per cent) and cystoscopy(28 per cent). Chemoprophylaxis was effective in reducing theserates in this patient group.     

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.     

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.     

Iron Overload, but not Treatment with Desferrioxamine Favours the Development of Septicemia in Patients on Maintenance Hemodialysis

During a 19-month period we determined the incidence of bacterialinfection among 39 patients treated with desferrioxamine whohad end-stage renal disease and were undergoing maintenancehemodialysis. Twenty-three received desferrioxamine becauseof aluminium-related bone disease, and 16 because of iron overload.A control group of 193 patients on maintenance hemodialysisbut without desferrioxamine was used. No difference was foundin the incidence of septicemia or of all bacterial infectionsbetween the patients with aluminium-related bone disease treatedwith desferrioxamine and the control patients (0.12 vs. 0.12septicemia per patient-therapy-year, p>0.05; 0.23 vs. 0.26bacterial infections per patient-therapy-year, p>0.05). Theincidence of septicemia in patients treated with desferrioxaminefor iron overload, however, was almost three times that in thecontrol patients (0.36 vs. 0.12 septicemia per patient-therapy-year,p<0.01). To assess the effect of iron overload itself, wedetermined the frequency of bacterial infection in patientson regular hemodialysis who have never received desferrioxamine.These were subdivided into three groups according to serum ferritinlevel which indicated normal or low iron stores (Group I: serumferritin 10-330 µg1/1, n=125), moderate (Group II: serumferritin 331-1000 µg/1, n=49) or more advanced iron overload(Group III: serum ferritin 1001-2000 µg/1, n=10). Comparedto patients with normal or low serum ferritin levels (GroupI), we found a significantly higher rate of bacterial infectionamong patients in Group II compared with Group I (0.18 vs. 0.34infections per patient-therapy-year, p<0.05) and Group IIIcompared with Group I (0.18 vs. 0.58 infections per patient-therapy-year,p<0.01). These results suggest that treatment with desferrioxaminedoes not favour the development of septicemia or bacterial infectionindependently of iron overload and that iron overload itselfmay predispose patients on regular hemodialysis to bacterialinfection.     

Endocrine Function, Psychiatric and Clinical Consequences in Patients With Macroprolactinomas After Long-term Treatment With the New Non-ergot Dopamine Agonist CV205-502

Although bromocriptine is the mainstay of treatment of macroprolactinomas,its therapeutic usefulness may be limited by poor tolerance,lack of consistent reduction in serum prolactin levels and tumoursize, and the necessity for multiple dosing. Consequently newdopamine agonists have been developed, including the long actingnon-ergot agonist CV205–502 which has been shown to dateto be consistently effective in reducing serum PRL levels andcausing tumour shrinkage. Twelve patients were treated for periods of up to 24 monthswith CV205–502 in doses ranging from 0.075 mg to 1.65mg once daily. Clinical and psychiatric assessments, biochemicalparameters, tumour size determination, and anterior pituitaryfunction tests were performed regularly. Tumour shrinkage wasnoted in all patients, and varied from 11 per cent reductionto complete disappearance of tumour. Prolactin levels becamenormal in seven patients and were reduced by more than 90 percent in the remaining five. Normal menstruation resumed in sixof the eight women, one of whom conceived after one year oftherapy; libido returned in all patients. Psychiatric complicationsoccurred in three patients necessitating withdrawal of therapyin one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5±0.1 to 1.0±0.1mmol/l at 12 months (p=0.006), and cholesterol fell from 6.3±0.4to 5.3±0.3 mmol/l (p=0.04). The mean TSH response 20min following TRH injection fell from 14.3±2.9 to 8.7±1.3mU/l at 2 months (p=0.027). There was a significant increasein the peak growth hormone response to the insulin stress testfrom basal median (25th–75th centiles) values of 15 (4.4–25.5)mU/l to 24.5 (9–37) mU/l at 2 months (p<0.01) and 31(19.3–63.5) at 12 months (p<0.005). CV205–502 is highly effective in the medical managementof patients with macroprolactinomas, reducing prolactin levelsand tumour size and restoring normal anterior pituitary function.It is, however, associated with the important side effects ofweight loss and pychiatric complications which should be drawnto the attention of clinicians.     

Percutaneous Transluminal Angioplasty for Atheromatous Renal Artery Stenosis - Blood Pressure Response and Discriminant Analysis of Outcome Predictors

Percutaneous transluminal angioplasty was performed in 39 consectivepatients with atheromatous renal artery stenosis associatedwith hypertension. The mean blood pressure before angioplastywas 191/107 mm Hg and this had dropped to a mean of 167/90 mmHG at the patient's most recent visit, representing a significantfall in both systolic (p<0.01) and diastolic pressures (p<0.001).The mean serum creatinine was 166.7 µmol/l before percutaneoustransluminal angioplasty and 155.3 µmol/1 at the mostrecent visit (not statistically significant. The mean numberof anti-hypertensive drugs fell from 2.4 to1.9 after percutaneoustransluminal angioplasty (p<0.05). Three patients (eightper cent) were ‘cured’ (diastolic blood pressure<90 mm Hg without medication), 25 (64 per cent) had ‘improved’(diastolic blood pressure <109 mmHg, with a fall of morethan 15 per cent) and 11 (28 per cent) had not improved. Logisticdiscriminant analysis showed that pre-percutaneous transluminalangioplasty diastolic blood pressure, age, serum creatinineand smoking habit together correctly predicted the outcome ofpercutaneous transluminal angioplasty in 90 per cent of patients,with four ‘false positives’ and no ‘falsenegatives’. Ten patients suffered, a total of 12 seriouscomplications related to the procedure: one death in acute renalfailure, one myocardial infarction, one severe hypotension,just after the procedure, one deep vein thrombosis, one episodeof transient ischaemia of the toes and seven groin haematomas.Thus percutaneous transluminal angioplasty for atheromatousrenal artery stenosis rarely ‘cures’ hypertension,but improved blood pressure control is often achieved, albeitat the expense of troublesome complications. A prospective,randomized trial is needed to establish whether or not the improvementis due directly to percutaneous transluminal angioplasty.     

Prevalence of Persistent Cough During Long-term Enalapril Treatment: Controlled Study Versus Nifedipine

The prevalence and severity of cough during long-term enalapriltreatment were examined by comparing a cohort of 136 hypertensivepatients who started treatment with enalapril with consecutiveage and sex-matched patients who commenced nifedipine therapyduring the same period. Cough and other symptoms were assessedby a questionnaire designed to avoid bias towards reportingcough. After a mean of 27 months' treatment patients on enalaprilhad an excess of persistent cough (16 per cent, 95 per centCI 7–25, p < 0.01), voice change (14 per cent, 95 percent CI 2–27, p < 0.05) and sore throat (10 per cent,95 per cent CI –0.1 to 20.3 per cent, p < 0.01) whencompared to nifedipine-treated patients. The cough was usuallydry, moderate or severe, paroxysmal, and troublesome at night.Cough tended to be more common in women (23 per cent vs. 7.2per cent), non-smokers, and at higher doses of enalapril, butwas not related to age, duration of treatment, or chronic respiratorydisease. Dry cough commonly persists as a troublesome side-effectduring long-term enalapril treatment, and is often associatedwith voice change and sore throat.     

The Determinants of Early Nephropathy in Insulin-dependent Diabetes Mellitus: A Prospective Study Based on the Urinary Excretion of Albumin

A four-year prospective study of the factors predicting albuminuriawas carried out in 172 normotensive, insulin-dependent diabeticpatients without overt nephropathy. Urinary albumin excretionwas estimated as the urinary albumin:creatinine ratio (U_A/U_C)in an early morning sample. Multivariate analysis showed thatU_A/U_C on the return visit was positively associated with theU_A/U_C (p<0.001) and glycosylated haemoglobin (HbA₁; p<0.001) at initial examination; weaker associations were foundwith a history of hospital admission (p<0.05) and smoking(p<0.05), and with treatment of blood pressure (p<0.05).Neither initial blood pressure, heart rate, nor creatinine clearancewere significant predictors of the U_A/U_C. Two patients diedfrom coronary heart disease, both of whom had raised albuminexcretion at initial examination. Eleven (6.8 per cent) of the160 patients who were studied repeatedly developed macroalbuminuria(U_A/U_C >45.5 mg/mmol): they had a significantly higher initialU_A/U_C (p<0.005), HbA₁ (p<0.05) and a greater frequencyof retinopathy (p<0.05) than patients matched for age, sexand duration of diabetes who did not develop macroalbuminuria.Simultaneous measurements of the U_A/U_C and HbA₁ should be usedwhen screening for microalbuminuria in diabetets mellitus: patientswith a high U_A/U_C(e.g. >3.5 mg/mmol) and HbA₁ (e.g. >13 per cent) should be closely monitored even when blood pressureis normal.     

Lupus Nephritis: Clinical and Pathological Correlation

Overall patient survival of 83 and 65 per cent at five and 10years respectively from onset of nephritis was similar to otherrecently published series. In contrast to the latter, the severeproliferative group had a significantly worse outcome than theother proliferative groups (p<0.01) and only patients inthis group progressed to end-stage renal failure. Haematuria was more common (p<0.05) in the severe group andthere was a striking correlation between histologic activityassessed semiquantitatively (Table 1) and urinary red cell count(p<0.001). There was no correlation between serum creatinine,proteinuria or chronic lesions with urinary red cell count.In contrast to a previous study there was no correlation betweenthe presence of hyaline thrombi on initial biopsy and subsequentdevelopment of glomerular sclerosis. Although the value of renal biopsy has been questioned, we suggestthat it remains a most important investigation in the managementof lupus nephritis. Determination of urinary red cell count provides a most usefulmonitor of disease activity and response to treatment.     

Hereditary Complement Deficiency in Survivors of Meningococcal Disease: High Prevalence of C7/C8 Deficiency in Sephardic (Moroccan) Jews

The prevalence of complement deficiency was studied among 111survivors of sporadic menin-gococcal disease located throughthe medical records of 10 Israeli hospitals. There were 11 patientswith CH₅₀=0: one with systemic lupus erythematosus and 10 withhereditary terminal complement deficiency (four with homozygousC7 and six with C8 deficiency). There was no hereditary complementdeficiency among 39 Ashkenazi subjects as against 18 per centamong 38 Sephardi subjects and 40 per cent among 15 of Moroccanancestry (p<0.05). The age at first presentation of meningococcaldisease in complement deficient patients was 14.7+7.6, yearscompared with 8.1+10.9 in the non-deficient patients (p<0.25).None of the complement deficient patients had meningitis belowthe age of 5 years vs. 49 per cent of non-deficient subjects.Recurrent meningitis was observed in 40 vs. 4 per cent (p<0.01)and meningitis in siblings in 40 vs. 2 percent respectively(p<0.001). In addition to the 10 propositi, 11 non-propositussiblings were identified with severe complement deficiency (sixwith homozygous C7 and five with C8 deficiency). Seven of thenon-propositi had no history at all of meningitis or any otherserious systemic disease, underlining the relatively favourableprognosis of terminal complement deficiency. With increasingfamiliarity with the clinical features of this hereditary disease,it is possible now to identify on clinical grounds patientswith meningococcal disease with a high likelihood of terminalcomplement deficiency.     

Study of Lupus Nephritis in Males

Clinical and pathological findings were studied in 23 male patientswith lupus nephritis who were followed up for a period of 41±36months after renal biopsy. Age at renal biopsy was 31±14years and 19 patients (83 per cent) were between 15 and 50 yearsold. C3 and C4 levels were below normal in 23 (100 per cent)and 16 (70 per cent) respectively, CH₅₀ was <25 u/ml in 67per cent, and antinuclear and anti-DNA antibodies were foundin 87 per cent and 82 per cent respectively. Serum albumin levelincreased from 2.9±0.8 g/dl to 3.7±0.8 g/dl duringthe follow up period (p<0.01), while urinary protein decreasedfrom 2.0±2.3 g/day to 1.4±2.5 g/day. There wasa significant improvement in the degree of haematurai (p <0.01),but serum creatinine levels showed no change (mean 1.5 mg/ml).Active proliferative lupus nephritis of, moderate or severedegree was observed in 65 per cent of patients at the initialbiospsy. A trend to regression in this activity was seen inmost serial biopsies, but the chronicity index showed a slightincrease. These data demonstrate that systemic lupus erythematosusin males, in comparison to our previous report of the diseasein female patients, is accompanied by more active nephritis,but that is follows a benign course with therapy.     

Nephrotic Range Proteinuria - A Good Predictive Index of Disease in IgA Nephropathy?

A combined retrospective and prospective study of 86 patientswith IgA nephropathy was conducted to determine whether thelevel of proteinuria was a good predictive index of progressivedisease. The patients fell into three groups: Group A, 31 patientswith proteinuria of less than 1g/day, Group B, 31 patients withproteinuria of 1 to 3.5g/day; and Group C, 24 patients withproteinuria of more than 3.5 g/day. The groups are comparablein age of presentation, sex ratio, and duration of study andshowed no difference in serum creatinine levels, creatinineclearance, incidence of hypertension or incidence of impairedrenal function. Compared with the patients in the other groups,those in Group C did not have increased incidence of progressivedisease. Nevertheless, they have a higher incidence of nephroticsyndrome (p<0.001), a lower incidence of macroscopic haematuria(p<0.05), lower serum albumin (p<0.05) and heavier proteinuria(p<0.01). Severity of proteinuria had no significant correlationwith the severity of renal histopathologic changes. Clinicalobservations divided the 24 patients with nephrotic range proteinuriainto three well-defined groups with different prognoses. Sixpatients had progressive disease with decreasing proteinuria.Five of these remained hypertensive and their initial renalbiopsy showed advanced pathologic changes. Thirteen patientshad persistent proteinuria although the renal function remainedunchanged. Three of these were treated with steroid but failedto respond, and their renal histopathologic changes were usuallymoderate. The remaining five patients showed good response tosteroid treatment although two became steroid-dependent. Theirrenal histopathology showed mild alteration. Our findings suggestthat severe proteinuria in IgA nephropathy does not inevitablyindicate a poor prognosis.     

The Relationship Between Long-term Glycaemic Control and Diabetic Nephropathy

Urine albumin excretion was studied by two widely accepted methodsin 210 patients with insulin-dependent diabetes mellitus andrelated to the mean of serial glycosylated haemoglobin (HbA₁)measurements made every 3 months during the previous 6 years.Microalbuminuria (albumin excretion rate > 20 µg/min)was present in 9.5 per cent of patients when defined by a 24-hourcollection and 8.1 per cent of patients when defined by a timedovernight urine sample. Those with microalbuminuria, as estimatedfrom a timed overnight urine sample, had a longer duration ofdiabetes but otherwise did not differ in age, duration of diabetesor arterial blood pressure from patients whose albumin excretionrate was 20 µg/min or less irrespective of the methodof urine collection. The mean and the most recent HbA₁ levelsdiffered significantly between the normal and the microalbuminuriagroups when defined by the 24-hour albumin excretion rate (p<0.001,p<0.01), but no significant difference between these groupswas found when albumin excretion rates were calculated fromthe timed overnight urine sample. Albumin excretion rate, examinedin relation to mean HbA₁, increased significantly with worseningglycaemic control whether measured over 24 hours or overnight(p<0.05, p< 0.01). These findings support an associationbetween glycaemic control and microalbuminuria, but the correlationis weak, dependent on the method of urine collection and isjust as good for a relatively short-term as for a long-termmeasure of average blood glucose.     

Antibodies to Cardiolipin in Stroke: Association with Mortality and Functional Recovery in Patients Without Systemic Lupus Erythematosus

Antibodies to cardiolipin were measured in 100 consecutive patientswith first ever stroke, on admission and at three and six monthsafter the acute event. One hundred healthy, age-and sex-matched,British elderly individuals were also screened for antibodiesto cardiolipin as a control group. Elevated levels of anticardiolipin antibody (i.e. 5SD abovethe laboratory control mean) were present in none of the controlgroup, but in 21 per cent of the patients with stroke. Thirteenof these 21 patients (62 per cent) died within three months,compared to 17 (21.5 per cent) of the seventy-nine patientswithout elevated levels of anticardiolipin antibodies (p<0.001).Six of the eight survivors with persistently elevated anticardiolipinantibodies had significant residual disability following stroke(Barthel score 0–9) compared to 11 of the 62 without (p<0.001).Two patients with initially raised anticardiolipin antibodieswho became independent at six months showed a progressive declinein the level of these antibodies to normal. The presence of high levels of anticardiolipin antibody didnot correlate with other recognized prognostic indices of stroke,except for incontinence. No correlation was noted between levelsof antibody to cardiolipin, antinuclear factor, antibody todouble-stranded DNA and C-reactive protein, either in the strokepatients or in the elderly control population. Hypertensionwas significantly more common in the patients with high anticardiolipinantibodies than in the rest of the patients in the stroke population(p=0.33). There was no correlation between levels of anticardiolipinantibody and age. Anticardiolipin antibody may be consideredas an independent prognostic marker for both mortality and clinicaloutcome after acute stroke.