Fluctuations of MS births and UV-light exposure.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.

BACKGROUND: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. METHODS: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. RESULTS: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). CONCLUSIONS: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.

MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis.

Observational cohort studies are a powerful tool to assess the long-term outcome in chronic diseases. This study design has been utilized in local and regional outcome studies in multiple sclerosis (MS) and has yielded invaluable epidemiological information. The World Wide Web now provides an excellent opportunity for an international, collaborative cohort study of MS outcomes. A web platform--MSBase--has been designed to collect prospective data on patients with MS. It is purely observational, enabling participating neurologists to contribute data on diagnosis, treatment and progress, to review anonymous aggregate data and to benchmark their patient population against other patient subsets or the entire dataset. MSBase facilitates collaborative research by allowing the online creation of investigator-initiated regional, national and international substudies. The registry aims to answer epidemiological questions that can only be addressed by prospective assessments of large patient cohorts. The registry is funded through the independent MSBase Foundation, and governed by an International Scientific Advisory Board. The MSBase Foundation commenced operations in July 2004 and since then, 22 neurologists from 11 countries have joined MSBase and are contributing 2400 patients to the total data pool.

Insulin autoimmune syndrome: the second Dutch case.

The insulin autoimmune syndrome (IAS) is the third leading cause of spontaneous hypoglycaemia in Japan. Here, we describe the second Dutch case. An 81-year-old man was analysed for collapse and attacks of disorientation, and was found to be hypoglycaemic during such an episode. The performed fasting test appeared to be positive. High levels of insulin and C-peptide postprandially and insulin antibodies were found. IAS was diagnosed.

Risk factors for the development of polyneuropathy and myopathy in critically ill patients.

BACKGROUND: Previously, mainly retrospective and a few important prospective studies postulated the role of sepsis or systemic inflammatory response syndrome (SIRS), multiple organ failure, and the use of medication as causative factors for the development of critical illness polyneuropathy and myopathy (CIPNM). This study aimed to identify the risk factors in the development of CIPNM. METHODS: Prospectively, we studied 98 patients who were on artificial respirators for the development of CIPNM. The Acute Physiology and Chronic Health Evaluation (APACHE) III score, presence of SIRS, and sepsis severity score at entry; the dosage of midazolam, vecuronium, and steroids at entry and day 7 of artificial respiration; and the use of aminoglycosides at entry were related with time to CIPNM or time of last follow-up. The Kaplan-Meier method and log-rank test were used. RESULTS: Thirty-two patients (33%) developed CIPNM. After multivariate analysis, it was found that the APACHE III score and the presence of SIRS were significantly related with risk for the development of CIPNM. No significant relation was found for the use of midazolam, vecuronium, or steroids. Based on a risk index from a Cox regression model with APACHE III score and presence of SIRS as outcomes, three groups could be constructed with low-, medium-, and high-risk patients for the development of CIPNM. CONCLUSIONS: The APACHE III score, a quantitative index of disease severity based on clinical and laboratory physiologic data, is a valuable predictor for the development of CIPNM in patients in the intensive care unit. Together with the presence of SIRS, it can be used to estimate the risk of developing CIPNM for patients on artificial respirators.

Evaluation and performance of the Coulter STKS.

The Coulter STKS is a fully automated haematology analyser which quantitatively measures and computes haematological quantities including a full "five-part" differential. The aim of this study was to evaluate whether the Coulter STKS can be used for screening purposes in a non-academic clinic. Results from the haemocytometry part of the apparatus correlated very well with those from the Coulter S Plus IV. Reasonable to good correlations were obtained with the standard manual 100-cell differential for neutrophils, lymphocytes, monocytes and eosinophils. Significantly higher percentages of monocytes were found by microscopic observation than by the STKS. Samples from 1080 patients were analysed on the STKS, and manual differentials were also performed. After revision of discrepancies and with the exclusion of neonatal samples, a good numerical agreement for the "five-part" differential was obtained. The STKS gave 1.8% false negatives, and both diagnostic sensitivity (96.3%) and specificity (83.3%) were high. A false negative rate of 1.9% was found for the indication left-shift, with a predictive value of a negative test of 97.4%. The predictive value of a positive test, however, was only 40.3%. An authorization procedure was implemented to reduce false negative samples. The routine laboratory work load for our differentials can be reduced by up to 70%. The Coulter STKS gave a high number of suspect flags for neonatal samples (75%) and is therefore not suitable for screening neonates.

Simplified and rapid methods for the determination of protein, fat and lactose in human milk and the energy intake by the breast-fed infant.

Triacylglycerides constitute the bulk of fat in human milk. By centrifuging the milk a layer of fat is obtained, the cream, the fraction of which correlates very well with the total triacylglyceride concentration. It is determined in analogy to the haematocrit and is called galactocrit). Protein is determined with the biuret method in defatted milk. The interference due to lactose in this assay is on average 2 g/l. Lactose is determined with an enzyme kit. The amount of macronutrients in milk determines the energy value. A protocol is proposed, which makes it possible to measure the quantity of human milk drunk by the infant and to calculate the daily energy intake.

The reactivity of thiol groups in bovine heart cytochrome c oxidase towards 5,5'-dithiobis(2-nitrobenzoic acid).

Bovine heart cytochrome c oxidase consists of 12 stoicheiometric polypeptide chains of at least 11 different types. The enzyme contains 14--16 cysteine residues; the distribution of nearly all cysteine residues over the subunits has been established. In native cytochrome c oxidase two thiol groups reacted rapidly and stoicheiometrically with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). These thiol groups are located in subunits I and III, respectively. This implies that subunit I is not fully buried in the hydrophobic core of the enzyme. After dissociation of the enzyme by sodium dodecyl sulphate more thiol groups became available to DTNB, in addition to those in subunits I and III, at least one in subunit II, two in fraction V/VI and one to two in the smallest subunit fraction. It is shown that separation of the subunits of cytochrome c oxidase by gel permeation chromatography in the presence of sodium dodecyl sulphate depends on the pH of the elution medium. The elution volume of subunits I, III and VII is dependent on pH, that of the others independent.

Subunit stoichiometry of cytochrome c oxidase of bovine heart.

Cytochrome c oxidase from bovine heart was dissociated into its protein subunits by sodium dodecylsulphate, the subunits were separated on a preparative scale by sodium dodecylsulphate gel permeation chromatography. The subunits elute upon gel chromatography in order of decreasing apparent relative molecular mass (I, 40000; II, 26000; III, 21000; IV, 17000; V and VI, 12000; VII, 10000 and VIII, 6000). The very hydrophobic subunits I and III tend to form small aggregates both in the presence and absence of sodium dodecylsulphate. The molar ratio of the subunits was determined by two methods: firstly by quantitative amino acid analysis of each subunit peak, and secondly from the absorbance of each subunit at 280 nm caused by tryptophan and tyrosine. We conclude that the subunits I to VI are present in 1 : 1 ratio; our fraction VII contains two stoichiometric polypeptides which may or may not be identical. Fraction VIII contains enough protein for four stoichiometric chains which may belong to three different types. The 12 stoichiometric chains add up to a Mr of about 170000 if the sizes of I and III are 40000 and 21000, respectively. After correction for the presence of aggregates, subunits I and III appear to be present in more than 1 : 1 stoichiometric amounts with respect to other subunits, which probably means that subunits I and III are considerably larger than hitherto assumed. This is in line with recently published mtDNA sequence work [Anderson, S. et al. (1981) Nature, 290, 457--465].

The isolation of bovine-heart cytochrome c oxidase subunits. Dependence on phospholipid and cholate-content.

The polypeptide chains of bovine-heart cytochrome c oxidase were preparatively isolated by a simple large-scale procedure based on gel permeation chromatography in the presence of sodium dodecyl sulphate. The resolution of the subunits as a function of the cholate and phospholipid content of the preparation was investigated. Cholate, and to a lesser extent, phospholipids interfere with the separation of the subunits; however, they do not prevent dissociation of the enzyme by SDS. Bovine-heart cytochrome c oxidase consists of six major subunits (estimated molecular weights in thousands: 40, 25, 20, 14, 12 and 10). In addition, the enzyme preparation contains at least five minor constituents, present in less than stoichiometric amounts. The first two of the three large subunits, all of which are hydrophobic, have amino-terminal N-formylmethionine. Subunit III, however, has a free methionine N-terminus.