Recurrent Bacteremia Caused by a “Flexispira”-Like Organism in a Patient with X-Linked (Bruton’s) Agammaglobulinemia

Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin.     

The interaction of Tamm-Horsfall protein with the extracellular matrix.

Tamm-Horsfall protein (THP) is the major glycoprotein component of urine, yet its biological role remains obscure. Recent reports have suggested that a concanavalin A (Con A)-binding fraction of THP from pregnancy urine can bind the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). In order to investigate this claim in relation to THP from normal adult urine we raised monoclonal antibodies to THP and sought THP/TNF-alpha interactions in three separate assay systems. We found no evidence that THP binds to TNF-alpha under physiological conditions, but we observed that it exerts a weak, probably not physiologically relevant, but reproducible inhibitory effect on the toxicity of TNF-alpha for monolayers of L929 cells, even when the cells are pretreated with the THP, and washed before addition of the cytokine. Since our preparations of THP do not interact directly with TNF-alpha we postulated an interaction with the cells themselves, or with their extracellular matrix. The THP was found by ELISA, immunoblotting and immunohistology, to bind to as yet unidentified components of the extracellular matrix in a manner dependent on cations, pH and carbohydrates. These data, considered in the light of the published amino acid sequence and biochemical properties, suggest that THP is a member of a structural glycoprotein family known to modulate cell adhesion.     

Bone mineral density in relation to medical and lifestyle risk factors for osteoporosis in premenopausal, menopausal and postmenopausal women in general practice.

BACKGROUND. Interest in the prevention of osteoporosis is increasing and thus there is a need for an acceptable osteoporosis prevention programme in general practice. AIM. A study was undertaken to identify a cohort of middle-aged women attending a general practice who would be eligible for a longitudinal study looking at bone mineral density, osteoporosis and the effectiveness of hormone replacement therapy. This study aimed to describe the relationship between medical and lifestyle risk factors for osteoporosis and the initial bone density measurements in this group of women. METHOD. A health visitor administered a questionnaire to women aged between 48 and 52 years registered with a Belfast general practice. The main outcome measures were menopausal status, presence of medical and lifestyle risk factors and bone mineral density measurements. RESULTS. A total of 358 women our of 472 (76%) took part in the study which was conducted in 1991 and 1992. A highly significant difference was found between the mean bone mineral density of premenopausal, menopausal and postmenopausal women within the narrow study age range, postmenopausal women having the lowest bone mineral density. A significant relationship was found between body mass index and bone mineral density, a greater bone mineral density being found among women with a higher body mass index. Risk factors such as smoking and sedentary lifestyle were common (reported by approximately one third of respondents) but a poor relationship was found between these two and all the other risk factors and bone mineral density in this age group. CONCLUSION. Risk of osteoporosis cannot be identified by the presence of risk factors in women aged between 48 and 52 years. In terms of a current prevention strategy for general practice it would be better to take a population-based approach except for those women known to be at high risk of osteoporosis: women with early menopause or those who have had an oophorectomy.     

Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole

A 64-year-old male with Aspergillus fumigatus infection that had disseminated from the lung to the ankle and adjacent bone was treated successfully with posaconazole after therapy with itraconazole and amphotericin B lipid complex failed. Marked clinical improvement occurred within 6 weeks of initiation of posaconazole therapy; after 6 months, infection had resolved at all sites. The patient has had no recurrence of infection.     

Effects of cytosolic Ca2+ on the Ca2+ content of the sarcoplasmic reticulum in saponin-permeabilized rat ventricular trabeculae

 Rat ventricular trabeculae were mounted for isometric tension recording, and then permeabilized with saponin. The Ca²⁺ concentration ([Ca²⁺]) within the permeabilized preparation (cytosolic [Ca²⁺]) was monitored continuously using Indo-1 and the integrals of Ca²⁺ transients resulting from brief caffeine application used as an index of the sarcoplasmic reticulum (SR) Ca²⁺ content. The relationship between SR Ca²⁺ content and cytosolic [Ca²⁺] was studied within the reported physiological range (i.e. 50–250 nmol · l^–1 Ca²⁺). Increasing cytosolic [Ca²⁺] from 50 nmol · l^–1 to 250 nmol · l^–1 increased the steady-state SR Ca²⁺ content about threefold. However, increasing [Ca²⁺] above 250 nmol · l^–1 typically resulted in spontaneous SR Ca²⁺ release, with no further increase in SR Ca²⁺ content. The SR Ca²⁺ content increased only slowly when cytosolic [Ca²⁺] was increased; it was unchanged 20 s after a rapid increase in cytosolic [Ca²⁺], but increased progressively to a new steady-state level during the following 1–2 min. In a parallel series of experiments using intact papillary muscles, increasing extracellular [Ca²⁺] (from 0.5 to 5 mmol · l^–1) significantly increased twitch tension within 20 s of the solution change. These results support previous suggestions that the SR Ca²⁺ content may increase when diastolic cytosolic [Ca²⁺] rises during inotropic interventions such as increased stimulus rate or extracellular [Ca²⁺]. However, the rate at which SR Ca²⁺ responds to changes in cytoplasmic [Ca²⁺] within the diastolic range does not appear rapid enough to explain the early potentiation of twitch tension in intact preparations after an increase in extracellular [Ca²⁺]. Received: 26 August 1997 / Accepted: 28 October 1997     

Cigarette smoking and random serum cholesterol levels in a Northern Ireland general practice population of 18- to 20-year-old students and non-students.

BACKGROUND: Coronary heart disease is the commonest cause of death in Northern Ireland, but few data exist on the incidence of risk factors in young adult students and non-students. AIM: To gather data on the prevalence of cigarette smoking and raised serum total cholesterol in a population of 18- to 20-year-old students and non-students. METHOD: Subjects were patients are Mountsandel Surgery, Coleraine on 1 January 1989 and were 18-20 years of age inclusive on that date. Subjects were interviewed by a research nurse who recorded socio-demographic data, tobacco consumption and random serum total cholesterol. Smoking status validation was by serum thiocyanate and expired air carbonmonoxide estimations. RESULTS: Out of the 832 subjects surveyed, 570 were students and 262 were non-students. Cigarettes were smoked by 239 (28.7%) subjects, and a significantly greater proportion of non-students compared with students were smokers (36.6% and 25.1%, respectively; P < 0.001). The proportion of males compared with females who smoked cigarettes was not significantly different, but males smoked significantly more cigarettes per day than females (14 and 11 cigarettes, respectively; P = 0.005). The average age for commencing regular cigarette smoking was 15.3 years, and 49.9% of smokers had started regular smoking by the age of 16 years. A greater proportion of non-students (65.7%) compared with students (39.2%) had started smoking before the age of 16 years. Out of those sampled, 156 (19.2%) had random serum cholesterol levels above 5.2 mmol l-1. Mean total cholesterol for non-students was significantly higher than for students (4.61 and 4.45 mmol l-1, respectively; P = 0.01) and increased significantly with increasing age (P = 0.03). Three subjects recorded cholesterol levels above 7.8 mmol l-1. CONCLUSION: Cigarette smoking and raised serum total cholesterol were prevalent among an apparently healthy population of students and non-students. These young adults may be significantly more at risk from subsequent coronary heart disease than was previously suspected.     

Phosphatemic action of 1,25-dihydroxyvitamin D3.

The action of a single intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was investigated in thyroparathyroidectomized (TPTX) vitamin D-deficient phosphate-depleted rats. After 14 h, plasma inorganic phosphorus (Pi) was significantly greater in animals receiving 1,25(OH)2D3 than in D-deficient controls, but urinary Pi excretion was very low in both groups and not significantly different in the rats given 1,25(OH)2D3. Clearance studies indicated that the D-deficient controls reabsorbed more than 99% of their filtered Pi. Avid Pi reabsorption continued even after the infusion of sufficient phosphate to raise the plasma and filtered Pi to approximately 3 times normal. Fractional calcium excretion (FECa) exceeded fractional sodium excretion (FENa) by severalfold, but FECa decreased strikingly during phosphate infusion. In animals that manifested a substantial elevation of plasma Pi after 1,25(OH)2D3, FECa was significantly less than in D-deficient controls. Therefore, the increase in plasma Pi following 1,25(OH)2D3 administration occurs independently of any effect on renal Pi reabsorption and may be responsible, at least in part, for the amelioration of hypercalciuria after 1,25(OH)2D3 treatment.     

Use of warfarin in non-rheumatic atrial fibrillation: a commentary from general practice.

Seven randomized trials published in the last six years have shown that warfarin reduces the risk of ischaemic strokes and death in patients with atrial fibrillation. The annual rates of major bleeding episodes in all these trials were low and, as a result, doctors in primary and secondary care are being encouraged to consider using warfarin for patients with atrial fibrillation unless there are obvious contraindications. However, the populations used in these studies were highly selected and rigorously monitored throughout the trial period to minimize the risk of bleeding in a way which probably could not be expected in routine primary care. Although the rates of major bleeding episodes were uniformly low, the rates of minor bleeding episodes were much higher and these could impact substantially on patients' views of the treatment and on the workload of the primary care team. Evidence is now at hand which allows the stratification of risk in patients with atrial fibrillation which should enable those who are at greatest risk to be considered for this form of treatment. Patients may develop risk factors over time which could render them unsuitable for continuation of warfarin therapy. The general practitioner is centrally placed to make the decision about initiating or continuing treatment or indeed stopping it. Several models for decision making in warfarin treatment from primary and secondary care are proposed.     

Relative frequency of VP4 gene alleles among human rotaviruses recovered over a 10-year period (1982-1991) from Japanese children with diarrhea.

The relative frequencies of the Wa (corresponding to serotype P1A), DS-1(P1B), M37(P2), and AU-1(P3) alleles of the VP4 gene from rotaviruses collected from the stools of individuals in Japan between 1982 and 1991 were determined to be 83.1, 15.6, 0, and 1.3%, respectively, by a polymerase chain reaction-based typing assay.