Acute renal failure due to leptospirosis: clinical features and outcome in six cases

Six cases of severe leptospiral infection with renal failure are described. Five of the six patients had acute oliguric renal failure requiring dialysis. Renal function recovered over three weeks and by two months all patients had plasma creatinine levels less than 200 mumol/litre. The initial diagnosis of leptospirosis depended on clinical and epidemiological features because serological confirmation was not possible during the first week of the illness. All the patients had either high risk occupations or a history of exposure to external sources of infection. All had fever, myalgia, jaundice and muscle tenderness. Although bilirubin levels were high (greater than 350 mumol/litre in five) the elevations of aspartate transaminase and alkaline phosphatase levels, and prolongations of prothrombin times were relatively slight. Thrombocytopenia occurred in five of the six cases. Leptospira complement fixation tests were weakly positive or negative on admission in five cases but rose to significant levels subsequently. Penicillin treatment resulted in Jarisch-Herxheimer reactions in three cases. The important complications were: upper gastro-intestinal haemorrhage (five cases), thrombocytopenia less than 30 000 platelets/mm3 (four cases), atrial fibrillation (three cases), drowsiness with asterixis (four cases). All six patients were seriously ill and required intensive supportive therapy. All survived.     

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.     

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.     

Experience in the Management of Hypertension with Unilateral Chronic Pylkonephritis: Results of Nephrectomy in Selected Patients

We report the experience of a aregional centre serving a populationof 3 millions in the management of patients with hypertyansionand unilateral scarred kidneys between 1972 and 1981. Thirtyone patients with hypertension and unilateral scarred kidneysbetween 1972 and 1981. Thiry one patients were studied, fifteenhavfe been subjected to nephrectomy and sixteen managed conservatively. The medically and surgically treated patients differed onlyin that the diseased kidney was smaller, 7.7±1.9 vs 9.9±1.7cm, (p<0.01), and systolic blood pressure higher, 224±34vs 198±30 mm Hg, (p=0.05), in the surgically treatedgroup. Following hephrectomy blood present pressure was normal withoutdrugs in four patients, control was made easier in only five.Serum creatinine did not increase folowing nephrectomy, buthad increased significantly at the time of the most recent followup in the medically treated patients (89 ± 20 to 102± 32 µmol 1–1, p < 0.05 ). We conclude that nephrectomy is of value in the management ofsome patients with unilateral chronic pyelonephritis and neednot results in loss of renal function. Renal vein renin studiesmay be helpful in selecting patients for surgery but examinationof the effect of nephrectomy in patients without differencesin renal vein is necessary to establish this. ^*Present address: Medical College, Berhampur 4, Ganjam, Orissa,India.     

Polyarteritis and the Kidney

We report data on 43 patients with polyarteritis affecting thekidneys. The majority (41 patients) had renal histological evidenceof microscopic polyarteritis. Although most patients (30 of43) had significant renal impairment at the time of diagnosis(serum creatinine >250 µmol/l) only five had a symptom,macroscopic haematuria, that directed attention to the kidneys.In the majority of patients in whom data was available therewas rapid deterioration in renal function between presentationand diagnosis. Renal function at diagnosis was worse in patientsaged over 50 of whom 20 out of 29 had a serum creatinine greaterthan 500µmol/l compared with only four of 14 patientsaged less than 50. The prognosis was worse in patients over50 (41 per cent died), in patients with a serum creatinine higherthan 500 µmol/l (54 per cent died) and in patients treatedwith intravenous methylprednisolone, (four also had intravenouscyclophosphamide) (38 per cent died). The major cause of deathwas sepsis and the actuarial one-year survival was 62 per cent.These results suggest that our approach to treatment shouldbe modified towards lessening immunosuppression in older patientsand in patients with renal failure at diagnosis.     

Ganciclovir Treatment for Cytomegalovirus Infection in Immunocompromised Patients With Renal Disease

The safety and efficacy of a 10-day course of ganciclovir therapywas assessed in 17 consecutive patients with proven cytomegalovirusinfection. The patients were receiving immunosuppressive therapyfor a variety of non-malignant renal conditions, including renaltransplantation (seven patients), small vessel vasculitis (sixpatients), systemic lupus erythematosus (three patients) andGoodpasture's disease (one patient). Fifteen patients were pyrexialat the time of their cytomegalovirus infection. Twelve patientshad pneumonitis manifesting as a pulmonary parenchymal infiltrateor a reduction in gas transfer. Fourteen patients had a significantlymphopenia (lymphocyte count <1x10⁹/l), nine were leucopenic(white cell count <3.5xtimes 10⁹/l) and nine had abnormalliver biochemistry. One patient had an infection of the ileumand one an infection of the larynx. All these disease manifestationsresponded completely to a single course of ganciclovir therapy.There were no clinical relapses and no side effects were observed. Ganciclovir is a safe and effective therapy when administeredearly in the course of cytomegalovirus infection in immunosuppressedpatients with renal impairment.     

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.     

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.     

Use of Liver Function Tests as Predictors of Rifampicin Metabolism in Cirrhosis

Normal subjects taking rifampicin regularly, show a fall inserum and urinary drug concentrations from enzyme inductionand increased biliary excretion. In cirrhosis, hepatocellulardysfunction and impaired biliary excretion may prevent thesechanges, but there is little information on how the drug shouldbe prescribed in such patients. Serum and urinary rifampicinconcentrations were therefore measured in thirteen patientsand five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower thanon Day 1 (7·0 ± 3·0 and 8·0 ±1·0 µg/ml respectively) and this was also the casefor nine cirrhotic patients with mild impairment of liver function(6·0 ± 1·0 and 11·0 ± 2·0µg/ml (p < 0·02). In both groups there was anaccompanying fall in urinary rifampicin excretion due to a decreasein desacetylrifampicin excretion. In the remaining four cirrhoticpatients, peak serum rifampicin levels rose from 11·0± 5·0 to 17·0 ± 6·0 µg/mland urinary excretion of desacetylrifampicin did not fall. Althoughvalues for serum albumin and prothrombin time were of limitedvalue in predicting drug accumulation, pretreatment levels ofbilirubin exceeding 50 µmolg/ml were present in all fourpatients showing an increase in serum rifampicin concentration.Furthermore, only in this group was there a rise in serum bilirubinduring treatment, almost certainly the result of competitionbetween rifampicin and bilirubin for hepatic uptake and excretion.In patients with cirrhosis, bilirubin concentrations exceeding50 µmol/l should be an indication for reduction in rifampicindosage.     

Komplikationen nach Hochdosistherapie und autologer Stammzelltransplantation Retrospektive Untersuchung an einem nicht selektionierten Patientenkollektiv

Zusammenfassung Hintergrund: Die Hochdosistherapie (HDT) mit autologer Stammzelltransplantation (ASZT) ist bei verschiedenen hämatologischen Tumoren zur Therapie der Wahl geworden. Obwohl die Neutropenie nach HDT nur kurz dauert, können lebensgefährliche Komplikationen auftreten. Bislang wurden nur wenige Arbeiten über die Komplikationen einer HDT mit ASZT bei unselektierten Patienten publiziert. Patienten und Methoden: Von 6/96 bis 12/99 wurden bei 42 Patienten 54 Transplantationen (neun Doppeltransplantationen, eine Dreifachtransplantation) durchgeführt. Der Altersmedian lag bei 55 Jahren (Spanne 25-74 Jahre). Das Geschlechtsverhältnis war ausgeglichen. 30 Patienten hatten hämatologische Neoplasien, zwölf waren an einem soliden Tumor erkrankt. Ergebnisse: Infektionen führten am häufigsten zu Komplikationen, danach folgte die Toxizität durch Mukosisis, Schmerzen oder Diarrhö. Bei vier Patienten fand sich eine positive Zytomegalie-Polymerase-Kettenreaktion (CMV-PCR). Zwei Patienten hatten Symptome entsprechend einer CMV-Erkrankung. Ein Patient erlitt eine busulfanbedingte Lungenfibrose und eine Lebervenenverschlusskrankheit. Zwei Patienten (4%) starben bei 54 Transplantationen an einer CMV-Pneumonie bzw. einem Multiorganversagen nach idiopathischer Pneumonie. Vier Patienten starben an einem Zweittumor (myelodysplastisches Syndrom zwei, solider Tumor zwei), wobei drei Patienten intensiv vorbehandelt waren. Wir untersuchten, ob die folgenden Faktoren die Komplikationsrate beeinflussten: Tumordiagnose (solide vs. hämatologisch), Anzahl der Vortherapien (< 2 vs. S: 2), Anzahl der CD34-positiven (CD34⁺) Zellen (< Median vs. S Median), Alter (⣗ Jahre vs. > 55 Jahre), Mukositis (WHO-Grad-1-2 vs. 3-4) und Transplantationsregime (myeloablativ vs. myelosuppressiv). Die Infektionsrate war bei Patienten mit myeloablativen Therapien höher als bei myelosuppressiv Behandelten, der Anstieg der Thrombozytenzahlen (15 vs. 9 Tage) langsamer. Eine höhere Anzahl CD34⁺ Zellen führte zu einem schnelleren Thrombozytentake (9 vs. 12 Tage). Bei Patienten mit mehr als einer Vortherapie traten mehr Infektionen auf (100% vs. 70%). Eine ausgeprägte Mukositis (WHO-Grad 3-4) führte sowohl zu einem langsameren Thrombozytenanstieg als auch zu mehr Infektionen. Keinen Einfluss auf die Komplikationen hatten die Tumordiagnose und das Alter. Schlussfolgerung: Die Komplikationsrate und die Mortalität unterschieden sich in dieser heterogenen Gruppe nicht von den Daten bei selektierten Patienten, bei denen ein definiertes Hochdosisprotokoll und eine bestimmte Tumorentität untersucht wurden. Die Komplikationsrate wird durch die Anzahl der Vortherapien, die Konditionierungstherapie und die Anzahl der transplantierten CD34⁺ Zellen beeinflusst. Abstract Background: High-dose therapy (HDT) with autologous blood stem cell transplantation (AST) has become the therapy of choice for patients with specific hematologic neoplasms. Although pancytopenia after HDT with stem cell support is of relatively short duration, complications may be severe and life-threatening. In unselected patients with hematologic and solid tummor malignancies, only few data have been published regarding complications. We therefore analyzed the rate of infection and toxicity in patients with different neoplasms undergoing HDT and ASCT. Patients and Methods: From 6/96 to 12/99 42 patients received 54 HDT and ASCT (nine tandem transplants and one triple transplant). The median age was 55 years (range 25-74 years) with equal sex distribution. 30 patients sufered from hematologic malignancies and twelve from solid tumors. Results: Infections were the major cause for complications followed by mucositis, pain and diarrhea. In four patients a positive cytomegalovirus polymerase chain reaction (CMV-PCR) was detected. In two patients this positive test result was accompanied by clinical symptoms of CMV infection. One patient developed lung fibrosis due to busulfan (WHO 4°) and additionally a veno-occlusive disease (VOD) of the liver (WHO 4°). Two patients (4%) died due to CMV pneumonia and multiple organ failure after idiopathic pneumonia, respectively. Four patients developed secondary neoplasms (two patients myelodysplastic syndromes, two patients solid tumors). Three of them had been heavily pretreated. We further analyzed whether the following parameters had an influence on the rate of complications: tumor diagnosis (hematologic vs. solid), number of pretreatment protocols (< 2 vs. S 2), CD34⁺ cell count (< median CD34⁺ cell count vs. S median CD34⁺ cell count), age (⣗ years vs. > 55 years), mucositis (WHO 1-2° vs. 3-4°) and conditioning regimen (myeloablative vs. myelosuppressive). The infection rate was higher in patients receiving myeloablative therapy compared to patients with myelosuppressive conditioning and the platelet count recovery was slower. In patients receiving a higher CD34⁺ cell count, time until platelets reached > 50/nl was shorter than in patients with a lower CD34⁺ cell count. Patients with S 2 pretreatment protocols had a higher infection rate than patients with < 2 pretreatments. Patients suffering from severe mucositis (WHO 3-4°) exhibited a slower platelet recovery and a higher infection rate. No difference was noted in the complication rate for the other parameters (tumor diagnosis, age). Conclusion: Complication rate and mortality in this heterogeneous patient group were not different from the data of other authors describing selected patients receiving a uniform conditioning regimen or having a distinct disease. The complication rate is influenced by the number of pretreatment protocols, conditioning regimens and the number of transplanted CD34⁺ cells.     

Prednisolone and chlorambucil therapy for idiopathic membranous nephropathy with progressive renal failure

Twenty-one patients with membranous nephro pathy, heavy proteinuriaand progressive renal fail ure were treated with alternatingmonthly cycles of corticosteroids and chlorambucil for six months.Four patients received repeat courses. After a median periodof follow-up of 39 months, three patients had died, six werereceiving renal replace ment therapy or had serum creatinine> 500 µmol/l, and one had progressive renal failure.Eleven patients had either stable or improved renal func tion,as judged by serum creatinine concentration. Of these eleven,four patients were in partial remis sion (daily protein excretion0.2–2.0 g), and two were in complete remission. Therewas a tendency for those who received intravenous methylprednisolone to have a more favourable outcome. There was a high incidenceof side-effects, with significant complications related to drugtherapy observed in >50% of subjects. Although individualpatients appeared to respond well, sometimes dramatically, theseresults are less encouraging than other reports. We would urgecaution in the use of this form of therapy, particularly inolder patients who may have occult neoplasms, impaired glucoseintolerance or pre–existing cardiac disease.     

Transjugular retrograde obliteration for chronic portosystemic encephalopathy

Chronic portosystemic encephalopathy (CPSE) is uncommon, and its management has yet to be determined. We have been able to control five cases of CPSE using transjugular retrograde obliteration (TJO), and we report our clinical results with this technique. All of the five patients were suffering from cirrhosis and had gastric varices and large gastrorenal shunts. According to Sherlock's classification, the grade of encephalopathy was II in two patients, III in two, and IV in one. According to Child's classification, one had class B and four had class C cirrhosis. TJO was performed using a 6-F angiographic catheter with an occlusive balloon 20 mm in diameter. Absolute ethanol and 5% ethanolamine oleate with iopamidol were used to obliterate the gastrorenal shunt. The gastrorenal shunt was successfully obliterated, and the encephalopathy improved to grade 0 after TJO in all cases. The portal flow volume increased significantly from 542 ± 189 to 992 ± 139 mL/min (p < 0.01). The plasma ammonia levels before and after TJO were 189 ± 40 and 51 ± 23 μg/dL, and the indocyanine green retention rates at 15 min were 44 ± 13% and 27 ± 12%, with both changes being significant (p < 0.01). Minor complications observed were fever of over 38°C and tarry stools due to hemorrhagic gastritis in one patient, which was being controlled conservatively. One patient died of hepatocellular carcinoma 27 months after TJO. The other four patients survived without recurrence of CPSE 17–74 months (44 ± 24 months) after TJO. We conclude that TJO can be adopted as a safe and effective treatment for CPSE. RID=" ID=" <E5>Correspondence to:</E5> F. Chikamori Received: 27 January 2000/Accepted: 23 February 2000     

Safety and efficacy of increasing wintertime vitamin D and calcium intake by milk fortification

We studied the safety and efficacy of milk fortified with vitaminD₃ and calcium. Over the winter, we conducted a double-blind,placebo-controlled trial of fortified milk (12µg vitaminD₃ and 1525 mg calcium per litre) compared to unfortified milk(0.3µg vitamin D₃ and 1270 mg calcium per litre) in 102adults (aged 17–54 years). Serum 25-hydroxyvitamin D [25(OH)D],ionized calcium, and creatinine were measured at baseline andafter intervention. Fortification reduced the seasonal declinein serum 25(OH)D concentrations by >50%. In the fortifiedgroup, serum 25(OH)D decreased by 15nmol/l from 77±35nmol/l to 62±26 nmol/l (p<0.001). In the control group,serum 25(OH)D fell by 31 nmol/l from 85±39 nmol/l to54±25 nmol/l (p<0.001). We suggest that milk enrichedwith vitamin D be provided in high-latitude European countriesto diminish the wintertime fall in serum 25(OH)D.     

The Effect of External Pituitary Irradiation on Elevated Serum Prolactin Levels in Patients with Pituitary Macroadenomas

The response of serum prolactin to external radiotherapy wasstudied in 58 patients (32 women) with pituitary tumours, agedbetween 16 and 75 years. Forty-four patients underwent pituitarysurgery before radiotherapy. Six Patients were irradiated witha regimen of 20 Gy in eight fractions over 10–11 daysand the remainder received 35–42.5 Gy in 15 fractionsover 20–22 days. Following radiotherapy, 44 patients receivedadditional treatment with dopaminergic agonists. Prolactin levelsranged from 1078 to 491000 mU/I (median 11750 mU/I) before radiotherapyand all but three patients showed a fall in serum prolactin(measured 4 weeks after stopping bromocriptine in those on dopamineagonist therapy) during observation over periods of up to 154months. All patients had evidence of pituitary fossa erosionor expansion at presentation and large tumours (Hardy-VezinaGrade 3–4) were more common in male patients (²=10.08,p<0.01). The rate of fall of serum prolaetin levels was greaterin patients with true prolactin-secreting tumours when comparedwith those who had stalk or hypothalamic damage (p< 0.005).The rate of decline of serum prolactin was also significantlyrelated to the pre-radiotherapy value (p=0.519, p<0.01).A serum prolactin level. <500 mU/I was achieved in 31 outof 44 patients treated with radiotherapy and dopaminergic agonistbut only nine remained normoprolactinaemic when medication wasdiscontinued for 4 weeks or more. The serum prolactin levelfell permanently to <500 mU/I in two of 14 patients treatedwith radiotherapy only. Actuarial analysis of data from allpatients indicated a 50 per cent probability that prolactinwould be reduced to <500 mU/I by 10 years; this increasedto 58 per cent for patients with smaller tumours (Hardy-Vezinagrade 2). Fourteen of 19 women of premenopausal age were amenorrhoeicbefore radiotherapy, but despite bromocriptine, menstruationwas restored in only five. A separate group of nine patientswith primary suprasellar, non-prolactin-secreting tumours andelevated prolactin levels was also studied. Prolactin concentrationsranged between 1016 and >4600 mU/I intially and were reducedby radiotherapy at a rate indistinguishable from that of patientswith pituitary adenomas associated with disconnection hyperprolactinaemia.None achieved permanent reduction of serum prolactin to <500mU/I. External radiotherapy is effective in reducing serum prolactinlevels in patients with pituitary macroadenomas, particularlywhere the hyperprolactinaemia is due to true tumour hypersecretion,but normal levels may take over 10 years to achieve. Radiation-inducedhypothalamic damage probably contributes to the hyperprolactinaemiapersisting after therapy and together with tumour-associatedor radiation-induced hypopituitarism accounts for the poor prospectsfor fertility in female patients.     

Low-dose Cyclopenthiazide in the Treatment of Hypertension: A One-year Community-based Study

After an 8-week placebo period, 73 patients whose diastolicblood pressures were between 90 and 110 mmHg were randomly assignedto receive 125 µg (low dose) or 500 µg of cyclopenthiazide(standard dose) for a period of one year. Blood pressure wasmeasured in the patient's home by the same observer at two-weeklyintervals during an 8-week placebo run-in period, every 4 weeksfor a further 12 weeks and at 24, 36 and 52 weeks thereafter.Serum potassium, urate, glucose, glycosylated haemoglobin, totaland HDL cholesterol, and apolipoproteins were measured at theend of the placebo period and at 4, 8, 24 and 52 weeks of activetreatment. Twelve of the 73 patients had an inadequate antihypertensiveresponse—five on the higher dose and seven on the lowerdose. One patient receiving 500 µg was withdrawn becauseof adverse effects. In the remaining 60 patients, systolic anddiastolic blood pressures were significantly reduced when comparedwith pretreatment values in both treatment groups throughoutthe one year period. The decreases in blood pressure were notsignificantly different from each other (p>0.65). Three patientson 500 µg required potassium supplements. Maximum decreasesin the serum potassium of 0.52 mmol/l(500 µg dose) and0.14 mmol/l(125 µg dose) were observed at 24 weeks oftreatment in the remaining 57 patients. The differences betweenthe two doses at this time were statistically significant (p< 0·05), as were the increases in serum urate observedat 4, 8 and 24 weeks (p<0.05). Five hundred micrograms ofcyclopenthiazide increased total serum cholesterol at eightand 24 weeks (0.35, 0.36 mmol/l respectively) when comparedwith pretreatment values (p<0.01) and almost achieved statisticalsignificance when compared with the corresponding low dose value(p = 0.066). This study confirms that 125 µg of cyclopenthiazideis a useful antihypertensive agent with a favourable metabolicprofile which is maintained in the long term.     

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.     

Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients

Background and objectives: FK 506 is an immunosuppressive macrolide advocated for prevention of graft rejection. Plasma or blood FK 506 levels must be determined to strike a balance between FK 506 toxicity and graft rejection. The first aim of this study was to compare an automated microparticle enzyme immunosorbent assay (MEIA) method (on whole blood) with the reference enzyme-linked immunosorbent assay (ELISA) method (on plasma). A second aim was to compare the two methods for prediction of FK 506 nephrotoxicity. Patients and methods: Forty-seven patients were studied comprising 128 samples. All were treated with FK 506 on a compassionate basis. For each patient, the concentrations of FK 506 were determined in plasma by means of ELISA and in whole blood by MEIA. Results: The repeatability and the reproducibility of these two methods were similar. The inter-patient correlation coefficient between MEIA and ELISA, determined on 128 samples from 47 liver recipients, was satisfactory (r=0.82). From these 47 patients, the intra-patient correlation coefficients were calculated for 17 of them. The intra-patient correlation coefficients were between 0.63 and 0.98 for 15 patients, and between 0.26 and 0.55 in the remaining two cases. Mean creatinine plasma levels in the 55 samples below the median FK 506 value in the MEIA method and in the 55 with values above the median (120 and 134 μmol/litre, respectively) were significantly different (P<0.05), as were those using the reference ELISA methods (115 and 139 μmol/litre, P < 0.01). In contrast, there was no significant difference between the mean creatinine plasma levels in the 55 samples with FK 506 levels below the median using both methods or between those above the median. Conclusion: The automated MEIA method, being simpler and more rapid than the ELISA method, should now be preferred for therapeutic monitoring of FK 506.     

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.     

Fever as the presenting complaint of travellers returning from the tropics

We investigated prospectively the cause of fever in patientsrequiring hospitalization after returning from the tropics.All consecutive admissions (n=195) with oral temperature >37.0°Cat the time of admission were enrolled. Final diagnosis as recordedon the discharge summary by the attending physician and resultsof any relevant laboratory or radiological investigations wererecorded on standard proforma. Malaria accounted for 42% ofadmissions; two patients had returned to Britain more than 6months before presentation. The second largest group was assumedto have a non-specific viral infection (25%). Cosmopolitan infections(urinary tract infection, community-acquired pneumonia, streptococcalsore throat, etc.) accounted for 9%. Coincidental infections(schistosomiasis, filariasis, intestinal helminths) were foundin 16%. Serology was positive for HIV infection in 3%. The mostuseful investigation was a malaria film, which was positivein 45% of cases in which it was performed. The combination ofthrombocytopaenia (platelet count <100 x 10⁹) and hyperbilirubinaemia(bilirubin > 18 IU/ml) were useful predictive markers ofmalaria: all 23 patients with both abnormalities had positivemalaria films. Malaria must be excluded in any febrile patientreturning from the tropics. In the absence of a positive malariafilm, the combination of a low platelet count and raised bilirubinmay suggest the need for an empirical course of therapy.     

Reinfection or recrudescence after apparently successful eradication of Helicobacter pylori infection: implications for treatment of patients with duodenal ulcer disease

Helicobacter pyloris is considered to be aetiologically implicatedin gastritis and peptic ulceration, since if H. pyloris infectioncan be eradicated the risk of subsequent ulcer relapse is markedlyreduced. The rate of ‘reinfection’ following treatment rangesfrom 0% to 45%, but its origin remains controversial (reappearanceof uneradicated original infection or a fresh infection). Todistinguish temporary suppression of H. pylori from fresh infectionwe conducted a retrospective analysis of the criteria used toestablish eradication of the original infection in 304 patients.We used the [¹⁴C]urea breath test, in which an integrated areaunder the curve (AUC) value of < 40 in 2 h is consideredto indicate eradication of H. pylori in patients tested 1 monthafter treatment. The results suggest that relapsed infection with H. pylori usuallyrepresents recrudescence of the original infection rather thana fresh infection; there was a higher relapse rate in patientswith a breath test AUC > 20 < 40, compared with thosewith an AUC < 20. All ‘reinfections’ occurredwithin 24 months of the original treatment. ‘Reinfection’was uncommon in patients receiving powerful therapeutic regimens(e.g. triple therapy) compared with those receiving monotherapyor relatively ineffective dual therapy combinations. In patientswhose urea breath test remains negative 12 months after treatmentthe subsequent reinfection rate is only 0.44%/ year. This supportsthe strategy of eradicating H. pylori infection from suitablepeptic ulcer patients.