Prevalence of scoliosis and impaired pulmonary function in patients with type III osteogenesis imperfecta.

PURPOSE: Osteogenesis Imperfecta (OI) is a rare group of congenital genetic disorders that consists of a collagen synthesis defect. The most severe phenotype is type III OI. Characterized by progressive bone deformity, fragility and pulmonary impairment, causing significant morbidity and mortality. Also, multilevel spine deformities are observed, such as scoliosis. The literature on the pathophysiology of pulmonary impairment in relation to scoliosis in these patients is scarce and conflicting. This study aims to determine the prevalence of scoliosis and its relation to pulmonary function in type III OI patients. METHODS: This retrospective cohort study took place between April 2020 and November 2021. Forty-two patients with type III OI were included. Anterior-posterior spine radiographs were evaluated for scoliosis. Pulmonary function was assessed using spirometry and partial pressure of carbon dioxide. RESULTS: All 42 patients had scoliosis, with a mean curve of 66° (95% CI of range). Vital lung capacity was decreased, compared to a non-OI population (mean 1.57 L). This was correlated to the degree of scoliosis (st. ß - 0.40, P = 0.03), especially in increasing thoracic curves. Restrictive lung pathophysiology was shown in our study population with a mean FEV1/FVC ratio of 0.85. CONCLUSIONS: Increasing thoracic scoliosis was correlated with decreased vital lung capacity in our study population of type III OI patients. High FEV1/FVC ratios found in this study population show restrictive lung pathophysiology. Therefore, it is plausible that the pulmonary impairment found in type III OI patients is a combined issue, partly associated to scoliosis and partly intrinsic to OI.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PURPOSE: The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). METHODS: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. RESULTS: At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. CONCLUSIONS: During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

BACKGROUND: In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. METHODS: In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. RESULTS: 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. CONCLUSION: Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

Validation of the 1 µg short synacthen test: an assessment of morning cortisol cut-off values and other predictors.

BACKGROUND: Clinical practice shows that many low-dose short synacthen tests (LD-SSTs) for diagnosing adrenal insufficiency in an outpatient setting have a normal outcome and could be considered superfluous. The objective of this study is to provide a guideline to safely reduce the number of unnecessarily performed LD-SSTs. METHODS: Data of LD-SSTs performed in outpatients were collected. Optimal morning cortisol cut-off values were determined using ROC analysis. Subsequently the predictive value of several variables was tested using univariable and multivariable logistic regression analyses. RESULTS: A morning cortisol lower cut-off value of 145 nmol/l (specificity 89.9%, positive predictive value 90.0%) and an upper cut-off value of 375 nmol/l (sensitivity 100.0%, negative predictive value 100.0%) were found. Chronic fatigue symptoms and symptoms of hypotension or orthostasis as the main reason for performing the test predict a normal outcome. The use of glucocorticosteroids predicts an abnormal outcome of the LD-SST. Oral, topical, nasal and inhaled glucocorticosteroids are each significant predictors when analysed specifically for predicting central adrenal insufficiency. CONCLUSION: By using morning cortisol cut-off values of 145 nmol/l and 375 nmol/l instead of the conventional cut-off values, the number of LD-SSTs performed in an outpatient setting can be reduced by 12%, while maintaining high sensitivity and specificity. Furthermore, the outcome of the LD-SST can be predicted by additional variables such as the indication for performing the test and the use of glucocorticosteroids. Different routes of administration of glucocorticosteroids such as inhalation or topical use should be taken into account when central insufficiency is suspected.

Minor disturbances in central nervous system function in familial neurohypophysial diabetes insipidus.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by a defect in vasopressin synthesis and release as a result of a heterozygous mutation in the gene for the vasopressin prohormone. The predominant characteristic of FNDI is excessive thirst and urine production. However, vasopressin not only has peripheral endocrine effects, but also regulates numerous brain functions. We investigated whether central functions are affected in FNDI, by studying neuropsychological functioning of 23 affected members (15 males, 8 females) of a large family carrying a T/G transition mutation at nucleotide 2110 (codon 116) of the vasopressin prohormone gene (Cys116Gly). The relatively large number of family members with FNDI made it possible to compare cognitive and other CNS effects in these subjects with those of family members without FNDI. Thirty-seven adult volunteers (20 males, 17 females) from the same family and 11 non-family members (2 males, 9 females) from northern part of The Netherlands were tested. The mean age of the subjects was 35+/-12 years. Of the 63 quantified neuropsychological parameters few were statistically different between the subjects with FDNI and control subjects. Memory retrieval processes and sustained attention were worse in the subjects with FDNI. Moreover, these individuals reported significantly fewer symptoms of agoraphobia and miscellaneous symptoms, and had significantly lower scores on a scale measuring anger. The performance of FNDI subjects on an auditory verbal learning test (the 15-word test learning trial) was worse, but not significantly so, than that of the subjects without FDNI. There were subjective complaints of forgetfulness and slow recalls and those were observed in daily life by non-affected family members. These moderate differences in neuropsychological performance indicate that in human FNDI parvocellular vasopressin systems that supply the brain may be less affected or give no such serious disabilities, than the magnocellular hypothalamo-neurohypophysial system that provides vasopressin for endocrine regulation of water homeostasis.

[Immunogenicity of biosimilars]. / Immunogeniciteit van biosimilars.

Biosimilars of more complex recombinant protein drugs, such as monoclonal antibodies and fusion proteins, are entering the market. The manufacturer should demonstrate that its product does not show any relevant differences in terms of quality characteristics, biological activity, safety and efficacy compared to the reference product, as outlined in EMA guidelines. This should be established with an extensive comparability exercise. One aspect that is subject to particular scrutiny is the immunogenicity of the biosimilar and the reference medicinal product. For three cases, one etanercept and two infliximab biosimilars, we describe how data are assessed and an opinion is reached by authorities. Not in all cases unanimity exists whether all remaining uncertainties on biosimilarity have been resolved satisfactorily before marketing authorisation. The Dutch Medicines Evaluation Board therefore emphasises that even after marketing authorisation, biosimilars and other biologicals should be properly monitored.

Tumor Recurrence or Regrowth in Adults With Nonfunctioning Pituitary Adenomas Using GH Replacement Therapy.

CONTEXT: GH replacement therapy (GH-RT) is a widely accepted treatment in GH-deficient adults with nonfunctioning pituitary adenoma (NFPAs). However, some concerns have been raised about the safety of GH-RT because of its potentially stimulating effect on tumor growth. OBJECTIVE: The aim of this study was to evaluate tumor progression in NFPA patients using GH-RT. DESIGN, SETTING, AND PATIENTS: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severely GH-deficient adults (1998-2009), all NFPA patients with ≥ 30 days of GH-RT were selected (n = 783). Data were retrospectively collected from the start of GH-RT in adulthood (baseline). MAIN OUTCOME MEASURE: Tumor progression, including tumor recurrence after complete remission at baseline and regrowth of residual tumor. RESULTS: Tumor progression developed in 12.1% of the patients after a median (range) time of 2.2 (0.1-14.9) years. Prior radiotherapy decreased tumor progression risk compared to no radiotherapy (hazard ratio = 0.16; 95% confidence interval, 0.09-0.26). Analysis in 577 patients with available baseline imaging data showed that residual tumor at baseline increased tumor progression risk compared to no residual tumor (hazard ratio = 4.5; 95% confidence interval, 2.4-8.2). CONCLUSIONS: The findings in this large study were in line with those reported in literature and provide further evidence that GH-RT does not appear to increase tumor progression risk in NFPA patients. Although only long-term randomized controlled trials will be able to draw firm conclusions, our data support the current view that GH-RT is safe in NFPA patients.

Cerebrovascular events, secondary intracranial tumors, and mortality after radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

CONTEXT: Radiotherapy is frequently administered as adjuvant treatment in patients with clinically nonfunctioning pituitary adenomas (NFPAs). However, concerns have been raised about potential long-term side effects, including cerebrovascular events (CVEs) and secondary intracranial tumors. OBJECTIVE: The aim of this study was to analyze the risk of CVEs, secondary intracranial tumors, and mortality in irradiated (IRR) NFPA patients, compared with NFPA patients who were not irradiated (non-IRR). DESIGN, SETTING, AND PATIENTS: The study cohort included 806 patients with a NFPA from the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide long-term surveillance study in severe GH-deficient adult patients. IRR patients (n = 456) were compared with non-IRR patients (n = 350). MAIN OUTCOME MEASURES: CVEs, secondary intracranial tumors, and mortality were measured. RESULTS: Sixty-nine subjects developed a CVE. In men, but not in women, the incidence of a CVE was significantly higher in IRR patients than in non-IRR patients (hazard ratio 2.99, 95% confidence interval 1.31-6.79). A secondary intracranial tumor developed in five IRR patients and two non-IRR patients. After adjustment for age, radiotherapy was not associated with mortality. CONCLUSIONS: The incidence of secondary intracranial tumors and mortality did not differ between IRR and non-IRR patients. However, a CVE was found significantly more frequently in IRR men but not in women. Further research into the long-term effects of cranial radiotherapy seems mandatory. The potential risks of radiotherapy have to be taken into account when radiotherapy is considered in NFPA patients, and long-term follow-up is recommended.

Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy.

Renin, prorenin, and immunoreactive renin were present in vitreous and subretinal fluid of eyes from subjects with and without diabetic retinopathy. Renin substrate, albumin, transferrin, and immunoglobin G were also found in these ocular fluids. In many samples renin levels were close to the detection limit of the assay. The levels of renin substrate, albumin, transferrin, and immunoglobulin G varied widely among ocular fluid samples, but in each individual sample the levels were, relative to each other, similar to those in plasma. In contrast, the prorenin level in ocular fluid was up to 100 times higher than expected on the basis of the plasma protein content of ocular fluid. Moreover, there was little difference in prorenin concentrations between samples with low and high plasma protein contents. Prorenin, relative to albumin and other plasma proteins, was higher in vitreous fluid from eyes with proliferative diabetic retinopathy complicated by traction retinal detachment than in eyes of nondiabetic subjects with spontaneous retinal detachment. It appears that prorenin (and possibly renin) in ocular fluid is controlled by an active and specific process, possibly local synthesis within the eye. In view of the vascular actions of angiotensin II, an intraocular renin-angiotensin system may play a role in diabetic retinopathy.

Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone.

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. We hypothesize that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone. Our data support the hypothesis that FNDI is a progressive neurodegenerative disease with delayed onset of symptoms. Its treatment requires early detection of symptoms for which growth parameters are useful.

High plasma prorenin in diabetes mellitus and its correlation with some complications.

Plasma prorenin is abnormally high, whereas renin is normal or even low, in many patients with long-standing diabetes mellitus complicated by microvascular disease. Nephropathy or autonomic neuropathy has been put forward as a cause. We found that in 223 consecutive diabetics prorenin correlated positively with serum creatinine, the presence of macroalbuminuria (greater than 250 mg/L), and the presence of diabetic retinopathy, particularly the proliferative type. This correlation did not depend on the presence of neuropathy or whether the patient was receiving insulin. It was also independent of sex, age, duration of diabetes, blood pressure, and blood levels of glucose and hemoglobin-A1c. The association between elevated prorenin and retinopathy remained significant after adjustment for creatinine and the presence of macroalbuminuria. Of the whole group of diabetics 94 consecutive patients were assessed for the presence of microalbuminuria (30-300 mg/24 h). Independently of the presence of micro- or macroalbuminuria, the mean level of prorenin was not above normal in the patients without retinopathy and was 2-3 times normal in those with proliferative retinopathy. Thus, retinopathy appears to be a more important determinant of abnormally high prorenin than nephropathy. In addition, the renal vein to artery ratio of prorenin in 7 diabetics with both advanced nephropathy and proliferative retinopathy was not elevated, despite the high peripheral venous prorenin level and the impaired renal perfusion. Thus, the abnormally high prorenin level in these patients could not be explained by abnormal secretion by the kidneys. Finally, prorenin was not high in 16 nondiabetics with loss of sympathetic activity due to chronic autonomic neuropathy, which indicates that in the absence of diabetes, this type of autonomic failure is not sufficient to cause the high prorenin levels seen in diabetics. Our findings are evidence that abnormally high plasma prorenin levels in diabetics are not an immediate consequence of altered glucose metabolism. This abnormality is related to the development of microvascular disease in the eye and kidney and is at least in part due to decreased clearance of prorenin from the circulation, increased production from extrarenal sources, or both.

A woman with bluish-coloured ears.

A 60-year-old woman presented with typical features of alkaptonuria.

[Identification of a new mutation (CysII6Gly) in a family with neurogenic diabetes insipidus]. / Identificatie van een nieuwe mutatie (CysII6Gly) bij een familie met neurogene diabetes insipidus.

OBJECTIVE: Elucidation and identification of the molecular biological alteration in the arginine-vasopressin neurophysin II AVP-NPII gene in a family with familial neurohypophysial diabetes insipidus (FNDI). DESIGN: Descriptive. METHODS: Following the finding of diabetes insipidus in a 2-year-old boy and his father a molecular genetic investigation was performed in the Isala Klinieken, Sophia location, in Zwolle, the Netherlands, to determine the nature of a possible gene mutation. Thereafter the AVP-NPII gene was screened in the family with polymerase chain reaction (PCR) and restriction enzyme analysis on DNA isolated from peripheral blood. An extensive pedigree was made. RESULTS: A new mutation in the AVP-NPII gene was identified in the part encoding the transport peptide neurophysin II. in exon 3, on codon 116, in which thymine was replaced by guanine, leading to the amino acid glycine instead of cysteine in the gene product. CONCLUSION: In a Dutch family with familial neurohypophysial diabetes insipidus a new gene mutation was found (CysII6Gly). Clarification of the molecular background of FNDI in this family made it possible to test family members in a relatively simple and friendly way (without the thirsting test) by PCR and restriction enzyme analysis for the presence of the mutation and the predisposition for diabetes insipidus.

Association of high plasma prorenin with diabetic retinopathy.

Plasma prorenin, but not renin, is elevated in long-standing diabetes mellitus. Nephropathy and autonomic neuropathy have been implicated as causes. However, we found no arteriovenous difference in prorenin across the kidney, despite high levels of circulating prorenin and a very low renal plasma flow, in five diabetics with combined end-stage nephropathy and proliferative diabetic retinopathy. Moreover, plasma prorenin was normal in 16 non-diabetics with autonomic neuropathy. The presence of a high level of prorenin was closely associated with the presence of diabetic retinopathy, particularly the proliferative type, in 223 consecutive patients. This association was independent of insulin requirements, metabolic control and of the presence of nephropathy or neuropathy. These data are evidence that part of the elevated plasma prorenin in diabetics is produced by an extrarenal source and that perhaps the eye affected by diabetic retinopathy is that source.

Dutch National Registry of GH Treatment in Adults: patient characteristics and diagnostic test procedures.

OBJECTIVE: The Dutch National Registry of GH Treatment in Adults was established in 1998 as an initiative of the Ministry of Health. The main goals were to gain more insight into long-term efficacy, safety, and costs of GH therapy (GHT) in adult GH-deficient (GHD) patients in The Netherlands. METHODS: Baseline patient characteristics and diagnostic test procedures were evaluated. RESULTS: Until January 2009 in roughly 10 years, 2891 patients (1475 men and 1416 women, mean age 43.5±16.5 years) were registered. GHD was of childhood-onset (CO) in over 20% of the patients and of isolated in 11%. The most common causes of GHD were pituitary tumors and/or their treatment, craniopharyngiomas, and idiopathic GHD. In 85% of the patients, a GH stimulation test was performed, in the majority an insulin tolerance test (ITT) (49%) or a combined GHRH-arginine test (25%). In 12% of the patients, IGF1 levels were ≤-2 s.d. combined with two or more additional pituitary hormone deficits, and in 2%, it concerned patients with CO-GHD continuing GHT in adulthood. Over the years, the test of first choice shifted from ITT toward GHRH-arginine test. CONCLUSION: Nearly, 2900 patients were included in the nationwide surveillance database of the Dutch National Registry of GH Treatment in Adults until January 2009. Baseline patient characteristics are comparable to that reported previously. In 85% of these patients, the diagnosis of GHD was established by provocative testing, particularly an ITT or a combined GHRH-arginine test, with an evident increase in the percentage of GHRH-arginine tests being performed in the last years.

Low prevalence of hypopituitarism after traumatic brain injury: a multicenter study.

OBJECTIVE: Hypopituitarism after traumatic brain injury (TBI) is considered to be a prevalent condition. However, prevalence rates differ considerably among reported studies, due to differences in definitions, endocrine assessments of hypopituitarism, and confounding factors, such as timing of evaluation and the severity of the trauma. Aim To evaluate the prevalence of hypopituitarism in a large cohort of TBI patients after long-term follow-up using a standardized endocrine evaluation. Study design Cross-sectional study. PATIENTS AND METHODS: We included 112 patients with TBI, hospitalized for at least 3 days and duration of follow-up >1 year after TBI from five (neurosurgical) referral centers. Evaluation of pituitary function included fasting morning hormone measurements and insulin tolerance test (n=90) or, when contraindicated, ACTH stimulation and/or CRH stimulation tests and a GH releasing hormone-arginine test (n=22). Clinical evaluation included quality of life questionnaires. RESULTS: We studied 112 patients (75 males), with median age 48 years and mean body mass index (BMI) 26.7±4.8 kg/m(2). Mean duration of hospitalization was 11 (3-105), and 33% of the patients had a severe trauma (Glasgow Coma Scale <9) after TBI. The mean duration of follow-up was 4 (1-12) years. Hypopituitarism was diagnosed in 5.4% (6/112) of patients: severe GH deficiency (n=3), hypogonadism (n=1), adrenal insufficiency (n=2). Patients diagnosed with pituitary insufficiency had significantly higher BMI (P=0.002). CONCLUSION: In this study, the prevalence of hypopituitarism during long-term follow-up after TBI was low. Prospective studies are urgently needed to find reliable predictive tools for the identification of patients with a significant pre-test likelihood for hypopituitarism after TBI.

Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes -- CORALL study.

OBJECTIVES: To compare the efficacy of the newest cholesterol-lowering drug, rosuvastatin (RSV) with atorvastatin (ATV) in subjects with type 2 diabetes. DESIGN: A 24-week, open-label, randomized, parallel-group, phase IIIb, multicentre study. SETTING: Diabetes outpatient clinics of 26 hospitals in The Netherlands. SUBJECTS: A total of 263 patients with type 2 diabetes treated with oral agents or insulin, age (mean +/- SD) 60 +/- 10 years, body mass index (BMI) 31.4 +/- 6.1 kg m(-2), 46% males. INTERVENTION: After a 6-week dietary lead-in period, patients were randomized to RSV (n = 131) or ATV (n = 132) treatment in a dose escalation scheme (RSV: 10, 20 and 40 mg or ATV: 20, 40 and 80 mg for 6 weeks each sequentially). MAIN OUTCOME MEASURES: Primary outcome was the change in apolipoprotein B (apoB) and apoB/apolipoprotein A1 (apoA1) ratio, which has been suggested a better predictor for cardiovascular events than total (TC) or low-density lipoprotein cholesterol (LDL-C). Secondary outcomes were the changes in other lipid parameters. RESULTS: Baseline LDL-C in the RSV and ATV groups was 4.23 +/- 0.98 mmol L(-1) and 4.43 +/-0.99 mmol L(-1), whilst apoB/apoA1 was 0.86 +/-0.22 and 0.92 +/- 0.35, respectively. A greater reduction in apoB/apoA1 was seen with RSV (-34.9%, -39.2% and -40.5%) than with ATV (-32.4%, -34.7% and -35.8%, P < 0.05 at weeks 12 and 18). Significantly greater reductions in LDL-C were also seen with RSV (-45.9%, -50.6% and -53.6%) than with ATV (-41.3%, -45.6% and -47.8%, all P < 0.05). The American Diabetes Association (ADA) LDL-C goal of < 2.6 mmol L(-1) was reached by 82%, 84% and 92% of patients with RSV and 74%, 79% and 81% with ATV. Triglyceride reductions ranged from 16 to 24% and were not different between treatments. Both treatments were well-tolerated: nine patients in the RSV and 11 in the ATV group withdrew from treatment because of adverse events after randomization. CONCLUSION: In subjects with type 2 diabetes, greater improvements of apoB/apoA1 and across the lipid profile were observed with RSV compared with ATV.

Isolation of salmonellas by immunomagnetic separation.

Magnetisable particles, coated with anti-salmonella serum, were used to isolate Salmonella livingstone from pure cultures, mixed cultures and food samples. Beads (10(7] were generally incubated with 10(4) Salm. livingstone cells/ml for 60 min at room temperature. The incubation and washing medium (0.01 mol/l phosphate-buffered saline; PBS) contained 0.1% bovine serum albumin (BSA) and 0.1% Tween 20, respectively. This method gave a recovery for Salm. livingstone of 51.0 +/- 7.8%. However, other micro-organisms such as Aeromonas hydrophila interfered with this test because of non-specific reactions (recovery 50.9 +/- 12.7%). These non-specific reactions could be decreased by using 4% skim milk instead of 0.1% BSA in the incubation medium. The ratio of the recovery of Salm. livingstone relative to the recovery of Aer. hydrophila changed from 0.9 when PBS with 0.1% BSA was used, to 13.4 when PBS with 4% skim milk was used. Immunomagnetic separation of Salmonella spp. from food samples offers good prospects for concentrating salmonella cells from heterogeneous bacterial suspensions, such as enrichment broths.

Plasma prorenin as an early marker of microvascular disease in patients with diabetes mellitus.

To test the hypothesis that a high plasma prorenin can be used as an early marker of microvascular complications in patients with diabetes mellitus plasma prorenin was measured in 44 patients with urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) and 120 patients with urinary albumin excretion below 30 mg/24 h (normoalbuminuria). A high plasma prorenin was associated with diabetic retinopathy, particularly the proliferative type, serum creatinine and the 24 h urinary albumin excretion rate. Plasma prorenin was not correlated with age, duration of diabetes, glycosylated hemoglobin, blood glucose, and blood pressure. The association between elevated plasma prorenin and retinopathy remained significant after adjustment for serum creatinine and albumin excretion. Independent of the presence or absence of microalbuminuria, the mean plasma level of prorenin was not above normal in patients without retinopathy and was 2 to 3 times normal in patients with proliferative retinopathy. Thus retinopathy appears to be an important determinant of abnormally high plasma prorenin. Angiotensin converting enzyme (ACE) was elevated in the patients with diabetes mellitus as compared to control subjects but the plasma levels of ACE in diabetics with normoalbuminuria was not significantly different from the group with microalbuminuria. Plasma prorenin was not associated with ACE. A plasma level of prorenin of 225 mU/L had a sensitivity of 0.84 and a specificity of 0.82 for detecting the presence of microalbuminuria.