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Since its discovery at the end of the nineteenth century, Moraxella (Branhamella) catarrhalis has undergone several changes of nomenclature and periodic changes in its perceived status as either a commensal or a pathogen. Molecular analysis based on DNA hybridisation or 16S rDNA sequence comparisons has established its phylogenetic position as a member of the Moraxellaceae and shown that it is related more closely to Acinetobacter spp. than to the genus Neisseria in which it was placed formerly. However, confusion with phenotypically similar Neisseria spp. can occur in the routine diagnostic laboratory if appropriate identification tests are not performed. M. catarrhalis is now accepted as the third commonest pathogen of the respiratory tract after Streptococcus pneumoniae and Haemophilus influenzae. It is a significant cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults, especially those with underlying chest disease. Nosocomial spread of infection, especially within respiratory wards, has been reported. Invasive infection is uncommon, but analysis of reports for England and Wales between 1992 and 1995 revealed 89 cases of M. catarrhalis bacteraemia, with the peak incidence in children aged 1-2 years. Carriage rates of M. catarrhalis are high in children and in the elderly, but its role as a commensal organism has probably been overstated in the past. Approximately 90% of strains are now beta-lactamase positive and, given that the first such strain was reported in 1976, this represents a dramatic increase in frequency over the last 20 years which has not been paralleled in any other species. The BRO-1 and BRO-2 beta-lactamase enzymes of M. catarrhalis are found in other Moraxellaceae, but are not related to beta-lactamases of any other species and their origin is therefore unknown. Molecular and typing studies have shown that the M. catarrhalis species is genetically heterogeneous and these methods have aided epidemiological investigation. Studies of factors that may be related to pathogenicity have shown the existence of three serotypes of lipooligosaccharide and the presence of fimbriae and a possible capsule. Some strains are serum-resistant, probably by virtue of interference with complement action, whilst transferrin- and lactoferrin-binding proteins enable the organism to obtain iron from its environment. An antibody response in humans to various M. catarrhalis antigens, including highly conserved outer-membrane proteins, has been demonstrated. Increased understanding of the organism's pathogenic properties and the host response to it may help to identify suitable vaccine targets or lead to other strategies to prevent infection. Whilst it remains, at present, the third most important respiratory pathogen, the impact of immunisation strategies for other organisms may change this position. The speed with which M. catarrhalis acquired beta-lactamase demonstrates the capacity of this organism to surprise us.
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PMID:Moraxella (Branhamella) catarrhalis--clinical and molecular aspects of a rediscovered pathogen. 915 30

Stainable iron in the liver (hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced liver disease. In chronic viral hepatitis, however, significant hepatocellular hemosiderosis is uncommon. This report describes unusual foci of hepatocellular hemosiderosis ("iron-rich foci" or IRF) in liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderin-negative liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.
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PMID:Iron-rich foci in chronic viral hepatitis. 949 Feb 68

Assessing vitamin and mineral supplement use is important because supplement use per se is an exposure of interest for the risk of several chronic diseases and because supplements contribute a large proportion of total (diet plus supplement) micronutrient intake, another important exposure in epidemiologic research. Unfortunately, little is known about methods for obtaining valid information about supplement use. The authors conducted a validation study in 1996 comparing supplement data collected in a telephone interview and from a self-administered questionnaire with data derived from a detailed, in-person interview and transcription of the labels of supplement bottles (i.e., a gold standard) among adult supplement users in Washington State (n = 104). Spearman correlation coefficients comparing average daily supplemental vitamin and mineral intake from the interview or questionnaire with the gold standard ranged from 0.76 (95% confidence interval 0.66-0.83) for vitamin C to 0.08 (95% confidence interval -0.14 to 0.29) for iron, with a mean of about 0.5. The principal sources of error were inaccurate assumptions about the micronutrient composition of multiple vitamins and respondent confusion regarding the distinction between multiple vitamins and single supplements. These results suggest that commonly used epidemiologic methods of assessing supplement use may incorporate significant amounts of error in estimates of some nutrients.
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PMID:Validity of methods used to assess vitamin and mineral supplement use. 977 70

High blood levels of glucocorticoids are associated with increased mortality, confusion and poor functional outcome in stroke patients. It has been proposed that inhibition of glucocorticoids in acute stroke might be beneficial, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administration of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was administered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb placements and ability to traverse a rotating pole were evaluated pre- and postoperatively. Infarct size, histology and GFAP immunoreactivity were evaluated on 5 microm coronal sections from brains perfused in situ 4 weeks after the ischemic event. Pretreatment did not influence outcome, whereas postoperative administration of metyrapone significantly increased infarct volume (P < 0.05). Post-treated rats performed significantly worse than vehicle-treated rats on the rotating pole 3 weeks after the operation (P < 0.05). Our results do not support the hypothesis that inhibition of glucocorticoid synthesis improves outcome after cerebral ischemia.
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PMID:Infarct volume and functional outcome after pre- and postoperative administration of metyrapone, a steroid synthesis inhibitor, in focal brain ischemia in the rat. 1036 3

In July 1996 a 43-year-old illiterate Hispanic woman presented with uncontrollable vomiting, palpitations and confusion. In 1994, despite several hospitalisations in other medical centres where a cerebral CT-scan, oesogastroduodenoscopy, colonoscopy and abdominal ultrasound were performed, no satisfactory diagnosis could be found. A psychiatric origin was finally considered. On admission, the laboratory findings showed severe metabolic alkalosis with associated hypokalaemia, confirmatory evidence of vomiting. The ECG showed tremendous P waves (5 mV) in the standard derivations, which can be explained by the hypokalaemia, with multiple supraventricular extrasystoles. Echocardiography and pulmonary scintigraphy ruled out pulmonary hypertension and a pulmonary embolus. After additional discussion with her daughter we discovered that the patient had been treating chronic headaches for years with 4-5 Cafergot-PB suppositories per day. This drug contains 2 mg ergotamine tartrate, 100 mg butalbital, 100 mg caffeine and 0.25 mg belladona alkaloids. As is known, vomiting is a classical symptom of ergotamine intoxication. After rehydration we discovered a megaloblastic anaemia with a folate deficiency compatible with chronic barbiturate intoxication. Folate and iron supplementation allowed a rapid normalisation of the haemoglobin values. Five months after having stopped the Cafergot-PB, the patient was well and did not vomit anymore. The headaches were treated with chlorpromazine with a good result. Despite sophisticated technical means, the diagnosis could only be established after a thorough history taking. This message should be heard in times when high tech medicine tends to obscure the place of a good history taking!
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PMID:[Intractable vomiting, convulsions and megaloblastic anemia: anamnesis, key to diagnosis]. 1043 23

Our ability to detect those predisposed to haemochromatosis is greatly enhanced by testing for HFE mutations. Ironically, this diagnostic advance has led to some confusion regarding the criteria for diagnosis of haemochromatosis, with overreliance on genetic testing instead of investigations for iron overload. Because many people who are homozygous for the C282Y mutation, or compound heterozygous for the C282Y and H63D mutations, either do not express or only partially express the disease, it is essential to confirm a diagnosis of haemochromatosis on the basis of increased body iron stores. Liver biopsy remains the best method of confirming this and has an important role in the patient with either borderline iron overload or advanced disease. Persistent elevation of serum ferritin concentration in the absence of overt liver damage, inflammation or neoplasia, and estimation of mobilized body iron by repeated phlebotomy, are reasonable alternatives to liver biopsy. Although the precise definition of iron overload is debated, a diagnosis of haemochromatosis cannot be made without demonstrating increased body iron stores.
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PMID:Haemochromatosis: iron still matters. 1145 37

Using the vocabulary of ballistics in medicine for emphasis can result in misleading exaggeration and semantic confusion. The dual meaning of target as either aiming point (aim at) or outcome (aim to achieve) creates a muddle in the efforts to comply with quality assurance initiatives. Disentangling the two meanings allows new approaches to the clinical technology required in a modern health care environment. An example can be shown in new strategies for the management of renal anemia with iron and erythropoietin. The potential to shape outcome distributions through validated, preemptive intervention thresholds offers the predictable results required by patients and payers. Using the management of patient cohorts as a platform for outcomes creates no necessary conflict with individualized clinical care. Future guideline statements should include the likely characteristics of compliant outcome populations, as a prompt to clinical goals and as an indication of the necessary cost and effort of compliance with treatment standards. Overemphasis in language is no substitute for considered clinical methodology.
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PMID:Targets and targeting. 1147 72

In a recent review published in this journal,(1) Koppenol traced the history of the Fenton reaction and of the catalytic decomposition of H(2)O(2) by iron salts. If his purpose was to shed light on current understanding of related chemistry in biological systems, he failed. Moreover, he managed to sow confusion by inaccurate reporting of the work of others. What follows is an attempt to point out these shortcomings and thus to clarify the situation.
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PMID:The Haber-Weiss cycle -- 70 years later: an alternative view. 1164 13

In answer to a question submitted to the journal, an expert explains the relationship between oral contraceptive (OC) use and levels of B6, and what, if any, symptoms altered B6 levels may cause in women using OCs. Use of OCs has been associated with decreased B6 levels. In 1 study, 80% of users had a relative B6 deficiency and 20% an absolute deficiency. Depression, a known complaint of OC users, is a symptom of B6 deficiency. Since users experience depression at a rate of 6.6%, research has been performed on the link between OC use, B6 deficiency, and depression. 2 studies are discussed: one in which 58 women complaining of premenstrual depression while on OCs were given supplements of B6; 31% experienced complete relief and a further 44% improvement of symptoms. In another double-blind study of 22 depressed women using OCs, placebo and B6 were administered in a cross-over fashion to 11 of these women who had absolute deficiency; they were given 20 mg of B6 or a placebo. All 5 of the 11 B6 deficient women given 20-mg of B6 improved according to clinical scores. Other symptoms of vitamin B6 deficiency include hyperirritability, convulsions, loss of appetite, loss of weight, general weakness, lassitude, confusion, and a hypochromic, microcytic anemia with a high serum iron level. There is agreement that vitamin B6 deficiency should be treated with additional vitamin intake and possibly OC discontinuation. B6 is an essential component of the cofactor pyridoxal phosphate, required for activating several body enzymes, and OCs apparently interfere with 5-hydroxtryptamine formation through interference with its decarboxylase. Depression in OC-using women is then thought to be due to low levels of brain serotonin (5-hydroxtryptamine).
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PMID:Any depression from OC-altered vitamin B6 levels? [Answer to question of Jan Marquand]. 1226 94

(5R)-Carbapen-2-em-3-carboxylic acid is the simplest structurally among the naturally occurring carbapenem beta-lactam antibiotics. It co-occurs with two saturated (3S,5S)- and (3S,5R)-carbapenam carboxylic acids. Confusion persists in the literature about the signs of rotation and absolute configurations of these compounds that is resolved in this paper. (3S,5S)-Carbapenam carboxylic acid was prepared from L-pyroglutamic acid to unambiguously establish its absolute configuration as identical to the natural product isolated from Serratia marcescens and from overexpression of the biosynthetic genes carAB in Escherichia coli. L-Proline labeled with deuterium or tritium at the diastereotopic C-5 methylene loci was shown to incorporate one label at the bridgehead of (3S,5S)-carbapenam carboxylic acid, but not into the "inverted" (3S,5R)-carbapenam carboxylic acid or the final carbapenem product. CarC, the third enzyme of the biosynthetic pathway required to synthesize the carbapenem, was demonstrated in cell-free studies to be dependent on alpha-ketoglutarate and ascorbate in keeping with weak sequence identities with other non-heme iron, alpha-ketoglutarate-dependent oxygenases. CarC mediated the stereoinversion of synthetic (3S,5S)-carbapenam carboxylic acid to the (5R)-carbapenem as judged by bioassay. These findings suggest that L-proline is desaturated to pyrroline-5-carboxylic acid prior to uptake into the biosynthetic pathway. The loss of the bridgehead hydrogen from the (3S,5S)-carbapenam during the ring inversion process to form the epimeric (3S,5R)-carbapenam and desaturation to the (5R)-carbapenem are proposed to be coupled by CarC to the reduction of dioxygen to drive the formation of these higher energy products, an unprecedented reaction for this enzyme class.
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PMID:Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline. 1284 54


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