Excipient exposure in very low birth weight preterm neonates.

OBJECTIVE: The excipients benzyl alcohol, propylene glycol and ethanol are present in medications used in the neonatal intensive care unit. Exposure to high levels can have adverse effects in a neonatal population. The objective was to quantify excipient exposure in very low birth weight (VLBW) neonates and identify risk factors associated with greater exposure. STUDY DESIGN: A retrospective record review of VLBW infants admitted over 1 year. Excipient exposures were calculated and multivariable regression analyses identified risk factors for increasing exposure. RESULTS: In total, 98% of subjects were exposed to at least one excipient. A total of 5 to 9% received doses higher than recommended for adults. Necrotizing enterocolitis, seizure, bronchopulmonary dysplasia and longer stay predicted higher excipient exposure. CONCLUSION: The excipients examined are in medications commonly prescribed for VLBW neonates, and cumulative doses may exceed recommended exposures for adults. Although safety profiles have not been established, judicious use of medication containing these excipients is warranted for this population.

St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up.

BACKGROUND: Diagnosis by screening mammography is considered an independent positive prognostic factor, although the data are not fully in agreement. The aim of the study was to explore whether the mode of detection (screening-detected versus symptomatic) adds prognostic information to the St Gallen molecular subtypes of primary breast cancer, in terms of 10-year cumulative breast cancer mortality (BCM). METHODS: A prospective cohort of patients with primary breast cancer, who had regularly been invited to screening mammography, were included. Tissue microarrays were constructed from primary tumours and lymph node metastases, and evaluated by two independent pathologists. Primary tumours and lymph node metastases were classified into St Gallen molecular subtypes. Cause of death was retrieved from the Central Statistics Office. RESULTS: A total of 434 patients with primary breast cancer were included in the study. Some 370 primary tumours and 111 lymph node metastases were classified into St Gallen molecular subtypes. The luminal A-like subtype was more common among the screening-detected primary tumours (P = 0·035) and corresponding lymph node metastases (P = 0·114) than among symptomatic cancers. Patients with screening-detected tumours had a lower BCM (P = 0·017), and for those diagnosed with luminal A-like tumours the 10-year cumulative BCM was 3 per cent. For patients with luminal A-like lymph node metastases, there was no BCM. In a stepwise multivariable analysis, the prognostic information yielded by screening detection was hampered by stage and tumour biology. CONCLUSION: The prognosis was excellent for patients within the screening programme who were diagnosed with a luminal A-like primary tumour and/or lymph node metastases. Stage, molecular pathology and mode of detection help to define patients at low risk of death from breast cancer.

The sensitivity and specificity of Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

AIM: To determine the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to detect an event of progression verified in serial stereoscopic ONH photography. METHODS: A retrospective study of 476 eyes of 342 patients with more than 18 months of follow-up with successful stereoscopic ONH photography was conducted. All eyes had good-quality HRT examinations with perfect image alignment. 51 (11%) eyes showed progression in the stereoscopic ONH photographs between visits. The photographs were evaluated by experienced masked observers, whose interobserver agreement (kappa) varied between 0.403 and 0.510. RESULTS: The change in most (13/22) of the stereometric ONH parameters showed a statistically significant correlation with progression. The parameter with the best correlation for progression (p<0.0005) was the cup:disc area ratio. The parameter with the largest area under the receiver operating characteristics curve (0.726) was the vertical cup:disc ratio. The linear discriminant function with the best correlation with progression was [(12.241xcup:disc area ratio)+(3.540xmean cup depth)-(2.146xhorizontal cup:disc ratio)+(27.486xaverage variability)]. An optimised change in the linear discriminant function value was 0.34 with a 65% sensitivity and a 69% specificity for progression. CONCLUSIONS: Despite good image quality, the change in the stereometric ONH parameters did not have a high sensitivity and specificity for progression detected with photographs. This indicates that the evaluation of glaucomatous progression in the ONH should not rely solely on the stereometric parameters of the HRT.

Calvarial doughnut lesions and osteoporosis: a new three-generation family and review.

Familial calvarial doughnut lesions (CDLs; OMIM 126550) is a rare autosomal dominant low bone density disorder characterized by distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. Only three families comprising 22 cases and 29 sporadic cases with the disorder have been reported. We describe a three-generation family consisting of three cases with clinical, radiological, biochemical, and histological findings consistent with this condition. All affected family members presented with childhood onset primary osteoporosis and typical CDLs or hyperostosis of the skull. In addition, the youngest family member was diagnosed with congenital glaucoma and her paternal grandmother with chronic congestive glaucoma. Glaucoma has not been previously described in this disorder. Adult patients also had recurrent cranial nerve palsies. No pathogenic mutations in the genes encoding low density lipoprotein receptor-related protein 5 (LRP5) or type I collagen (COL1A1 or COL1A2) were identified, suggesting that the disorder is caused by another dominant, yet unidentified gene. The literature is reviewed.

Effectiveness of antihypertensive treatment in chronic renal failure: to what extent and with which drugs do patients treated by nephrologists achieve the recommended blood pressure?

Adequate control of blood pressure (BP) is important to slow the progression of chronic renal failure (CRF). The Joint National Committee (JNC) VI recommends BP <130/85 mmHg, or <125/75 mmHg if urinary protein excretion exceeds 1 g/d. Angiotensin converting enzyme inhibitors (ACE-I) are considered as first-line agents. The current study is a survey of the degree of goal achievement and prescription patterns of antihypertensive (AHT) medication according to the JNC guidelines in clinical nephrology practice. All patients with CRF, not on renal replacement therapy, treated by nephrologists at the University Hospital of North-Norway were included in this retrospective cross-sectional study. Data on protein:creatinine ratio (PC ratio), BP and AHT drugs prescribed were extracted from the hospital's databases and medical records. A total of 144 patients were included. The patients' age was 62+/-16 years and the serum creatinine value was 210+/-92 micromol/l (mean+/-s.d.). In all, 74 patients (51%) had PC ratio < or =1, 36 (25%) >1, and for 34 (24%) PC ratio had not been measured; 23 (31%) of the patients with PC ratio < or =1 had BP < or =130/85 (139+/-21/78+/-12), and 5 (14%) of those with PC ratio >1 had BP < or =125/75 (145+/-22/85+/-14). Failure to achieve the goal was most commonly due to elevated SBP. In all, 55 % of the patients were prescribed ACE-I or angiotensin receptor blocker (ARB). In conclusion, the recommended BP goals may be difficult to achieve for a high proportion of patients in clinical practice due to difficulty in lowering SBP. There is a potential for improved treatment of hypertension in CRF patients, including increased prescription of ACE-I and ARB.

Cross-contamination in Porcelain Mortars.

Porcelain mortars and pestles are frequently used to comminute drug substances on a small scale and (in some cases) in the production of liquid and semisolid suspensions. Although it is generally accepted that removal of a drug substance from a rough surface by rinsing may be difficult and may lead to cross-contamination, no hard data support that theory. In this study, the amount of salicylic acid remaining on a porcelain mortar after different washing procedures was quantified and compared with the amount remaining on a plastic mortar. Drug residues in the "mg" range on the porcelain mortars made common rinsing procedures appear inappropriate, but no traces of drug were detected on plastic mortars. In addition, the quality of suspension ointments with respect to particle size and homogeneity produced by the two types of mortars was compared. Porcelain and plastic mortars appeared equally suitable for use in the production of semisolid suspensions.

Use of QRA for decision support in the design of an offshore oil production installation.

QRA is today widely used as a tool for decision support in the offshore industry. Its use has gradually changed from a prescribed analysis for verification purposes to a tool being actively used in an integrated mode. The paper describes its use in the design of a modern offshore platform. The paper addresses work methodology, selection of tools and data, organisation of QRA with other activities. Specific examples are given.

Diabetic cataract in children.

PURPOSE AND METHODS: Adolescent patients with insulin-dependent diabetes mellitus (IDDM) were retrospectively analyzed for the occurrence and possible predisposing factors of diabetic cataract in a population-based series of some 600 pediatric diabetics followed up during the years 1975-1995. RESULTS: Six patients (1%) needed cataract surgery. At the diagnosis of cataract they were 9.1-17.5 years old, and the duration of diabetes was between 0 months and 3 years 11 months. The type of cataract was similar in all patients characterized by bilateral snowflake type cortical deposits and posterior subcapsular cataract. Four of the six patients had at least a six-month history of diabetic symptoms before the treatment was started, and five patients had ketoacidosis at initial admission to hospital. In one of the 11 operated eyes diabetic retinopathy was observed immediately after surgery. Three patients developed proliferative retinopathy within 7-10 months after the operation, after 6.3-11.8 years of diabetes. CONCLUSIONS: The prevalence of diabetic cataract was around 1% in the pediatric diabetic population. In the pathogenesis of cataract long duration of diabetic symptoms and ketoacidosis prior to the commencement of treatment may be of significance. Good metabolic control after diagnosis did not protect for cataract. Diabetic cataract can safely be treated by modern surgical techniques, but close monitoring of the fundi for retinopathy after the operation is crucial, as proliferative retinopathy may develop rapidly after cataract surgery despite relatively short duration and acceptable metabolic control of diabetes.

Genetic markers in early diabetic retinopathy of adolescents with type I diabetes.

The aim of this study was to evaluate the role of HLA (human leucocyte antigen) class I (A, B, C) and class II (DR) alleles and familial insulin-dependent diabetes mellitus as possible risk markers for early retinopathy in a population of 103 Finnish adolescents with type I diabetes mellitus for 3.6-16.2 years. Fifty-one of the patients (49.5%) had signs of retinopathy in fundus photographs. HLA DR1 was found in 31% of the subjects with retinopathy, but in only 5% of those without retinopathy (p = 0.02). The corresponding figures for HLA DR1/4 were 17% and 2.6%, respectively (p = 0.22). The frequency of HLA DR3, DR4, or DR3/4 heterozygosity did not differ between the two groups of patients. Signs of early retinopathy showed thus an association with the presence of the HLA DR1 allele, and a mild protective effect of the HLA A9 and B40 alleles was indicated. Other HLA A, B, C, or DR alleles did not have any effect on the risk for early development of retinopathy, neither had a positive family history of type I diabetes.

Retinal vasodilation and hyperglycaemia in diabetic children and adolescents.

Retinal vessel diameters of 45 diabetic children and adolescents with diabetes were measured on black-and-white fundus photographs (negatives) using digital image analyses technique and microdensitometry as well as with direct micrometry. The changes in vessel diameters in two sets of photographs taken at an interval of 2.4 +/- 0.3 years were compared with glycated haemoglobin level, retinopathy status and various other parameters. During the follow-up period both arterial and venous diameters increased significantly (p = 0.0436 and p = 0.0001, respectively), but the changes in individual vessels and between patients differed markedly. The superior temporal vein dilated more than the inferior temporal vein. The average increase in venous calibre was related to the glycated haemoglobin level on the date of the second examination (p = 0.0492). Signs of early retinopathy developed more often in the eyes with venous dilation (6 of 18 eyes) than in those without (3 of 24 eyes), but the difference did not reach statistical significance. The results indicate that retinal vasodilation is associated with chronically elevated blood glucose level in diabetic children, and may precede development of other signs of retinopathy.

Prevalence and risk factors of retinopathy in children with diabetes. A population-based study on Finnish children.

The prevalence of retinopathy in children with insulin-dependent diabetes mellitus (IDDM) was studied in a population-based survey on 194 of the 216 subjects (89.8%) with IDDM aged 4.6 to 16.6 years living in the county of Oulu, Finland. The diagnosis of retinopathy was based on fundus photography. The median age of the children was 12.2 years and the median duration of diabetes 4.5 years (range 0.14.2 years). Retinopathy was found in 21 (10.8%) of cases. All of the changes seen were mild and did not require treatment. All the children with retinopathy were pubertal or postpubertal, and an association was found between the presence of retinopathy and the long-term diabetes control, duration of diabetes, age and albuminuria. Logistic regression analysis showed increasing duration of diabetes, puberty and elevated blood glycated haemoglobin to be the main risk factors explaining the occurrence of retinopathy. In patients aged 13-16 years retinopathy was also related to female sex and diastolic blood pressure, but in logistic regression analysis duration of diabetes and glycated haemoglobin were the best predictors.

White spots in the central fundus in diabetic children and adolescents.

Previously, small defects in the retinal pigment epithelium appearing as depigmented spots in the fundus photographs have been observed in a high proportion of adult diabetic patients. In order to evaluate whether these changes already occur in children we examined the black-and-white and colour fundus photographs of 206 diabetic children aged 4.6-19.6 years (median 12.6), with the median duration of diabetes of 4.7 years (range 0.0-14.2). Early signs of retinopathy were observed in 27 (13.1%) of them. The control group was composed of 45 healthy children aged 8.1-16.6 years (median 11.8). One or more tiny white spots in the fundus of one or both eyes were observed in 97 diabetics (47.1%), more often in those with retinopathy than in those without (66.7% vs. 44.1%, p less than 0.001). In the control group similar spots were observed in 24 children (53.5%). Only in a small proportion of children (4.4% of both diabetic and control patients) were the spots numerous. In children most of the white spots in the fundus may represent drusen type deposits rather than defects in the pigment epithelium.

Prevalence of HIV antibody among a group of paraphilic sex offenders.

Serum specimens from 77 paraphilic sex offenders in treatment at a major community-based sexual disorders clinic were examined for human immunodeficiency virus (HIV) infection. In addition to their paraphilic ("sexually deviant") activities, most patients had also had nonparaphilic sexual contacts with consenting adult partners. These patients had engaged in a variety of sexual behaviors that involved real or potential exchange of body fluids. In spite of that fact, data analysis revealed that none of the 77 paraphilic patients was seropositive for HIV infection as assessed by recombinant enzyme-linked immunosorbent assay (ELISA).