Colin Borland

Significant blood resistance to nitric oxide transfer in the lung

Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO<infinity. We now show in a membrane oxygenator model perfused with whole blood that addition of a cell-free bovine hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit (D) for NO (DNO) by 39%, D for carbon monoxide (DCO) by 24%, and the ratio of DNO to DCO by 12% (all P<0.001). In three anesthetized dogs, DLNO and DLCO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DLNO/DLCO=4.5. After exchange transfusion, DLNO rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DLNO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo thetaNO [5.1 ml NO.(ml blood.min.Torr)(-1)] approached 4.5 ml NO.(ml blood.min.Torr)(-1), which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

The TL,NO/TL,CO ratio in pulmonary function test interpretation

The transfer factor of the lung for nitric oxide (TL,NO) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (TL,CO). Physiologically, TL,NO predominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton–Forster equation, TL,NO acts as a surrogate for the membrane diffusing capacity (DM). The red blood cell resistance to carbon monoxide uptake accounts for ∼50% of the total resistance from gas to blood, but it is much less for nitric oxide. TL,NO and TL,CO can be measured simultaneously with the single breath technique, and DM and pulmonary capillary blood volume (Vc) can be estimated. TL,NO, unlike TL,CO, is independent of oxygen tension and haematocrit. The TL,NO/TL,CO ratio is weighted towards the DM/Vc ratio and to &agr;; where &agr; is the ratio of physical diffusivities of NO to CO (α=1.97). The TL,NO/TL,CO ratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. The TL,NO/TL,CO ratio is a new index of gas exchange that may, more than derivations from them of DM and Vc with their in-built assumptions, give additional insights into pulmonary pathology.

Standardisation and application of the single-breath determination of nitric oxide uptake in the lung

Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath DLNO. This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar “collection” or continuously sampled via rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4–6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40–60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1 of blood; 6) the equation for 1/θCO should be (0.0062·PAO2+1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding PAO2 and adjusted to an average haemoglobin concentration (male 14.6 g·dL−1, female 13.4 g·dL−1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity. Pulmonary diffusing capacity for nitric oxide is standardised by a panel of experts for use around the world http://ow.ly/TpV1306Yhji

Carbon monoxide yield of cigarettes and its relation to cardiorespiratory disease

Estimates of the carbon monoxide yield of their cigarettes have been obtained for 4910 smokers (68% of all smokers) in the Whitehall study of men aged 40 to 64. In the 10 years after examination 635 men died. When men smoking cigarettes with high carbon monoxide yield were compared with those smoking cigarettes with a low yield, and after adjusting for age, employment grade, amount smoked, and tar yield, the risk of death was 32% lower for coronary heart disease, 49% higher for lung cancer, and 10% lower for total mortality; these differences were not statistically significant. Among men who said that they inhaled the risk of fatal coronary heart disease was 51% lower in the high carbon monoxide group (p less than 0.01), while the risk of lung cancer was 75% higher. These results provide no evidence that a smoker can reduce his risk of death by smoking a brand with a low carbon monoxide yield; he might even increase it. The complex interactions between characteristics of the smoker, smoking behaviour, constituents of tobacco smoke, and health are again demonstrated.

Femoral vein thrombophlebitis and septic pulmonary embolism due to a mixed anaerobic infection including Solobacterium moorei: a case report

BackgroundPrimary foci of necrobacillosis infection outside the head and neck are uncommon but have been reported in the urogenital or gastrointestinal tracts. Reports of infection with Solobacterium moorei are rare.Case presentationA 37-year-old male intravenous drug user was admitted with pain in his right groin, fever, rigors and vomiting following a recent injection into the right femoral vein. Admission blood cultures grew Fusobacterium nucleatum, Solobacterium moorei and Bacteroides ureolyticus. The patient was successfully treated with intravenous penicillin and metronidazole.ConclusionThis case report describes an unusual case of femoral thrombophlebitis with septic pulmonary embolism associated with anaerobic organisms in a groin abscess. Solobacterium moorei, though rarely described, may also have clinically significant pathogenic potential.

Methemoglobin Levels in Smokers and Non-Smokers

The authors analyzed the blood of a group of 336 smokers and 336 non-smokers to determine if tobacco smoke, potentially the major source of nitrogen oxide pollution for 40% of the adult population, significantly reduces oxygen carrying capacity as a result of methemoglobin formation. Each blood sample was analyzed for carboxyhemoglobin, methemoglobin, and hemoglobin using an automated spectrophotometer. The mean value of methemoglobin in the smokers did not exceed that in the non-smokers; in fact, the level in the non-smokers was significantly greater. As expected, carboxyhemoglobin levels in smokers substantially exceeded those in non-smokers. The authors conclude that methemoglobin arising from cigarette smoke exposure does not interfere with the oxygen carrying capacity of the blood in smokers.

Fatal Israeli Spotted Fever in a UK Traveler to South Portugal

A 63-year-old previously healthy woman developed a severe systemic infection 5 days after returning from a holiday to Southern Portugal. She subsequently died, and polymerase chain reaction of a blood sample was positive for Rickettsia conorii ssp israeliensis. The prevalence of severe forms of this illness in the Mediterranean Basin is discussed.

Persistent orocutaneous and anal fistulae induced by nicorandil: a case report

IntroductionAlthough nicorandil is prescribed widely, awareness of its potential to cause serious complications to the gastrointestinal tract mucosa is limited. Whilst nicorandil-induced oral and anal ulceration is well documented in the literature, nicorandil-induced fistulation is not. This is the first report in the literature of a single patient demonstrating simultaneous orocutaneous and anal fistulae during nicorandil therapy. Two separate cases of orocutaneous and anal fistulae associated nicorandil usage have previously been documented in specialist journals.Case presentationA 71-year-old Caucasian man presented with a 3-year history of concurrent orocutaneous and anal fistulae. He had been exposed to 30 mg twice-daily nicorandil therapy for 4 years. Both fistulae responded poorly to intensive and prolonged conventional treatment but healed promptly on reduction and eventual withdrawal of nicorandil therapy.ConclusionManagement of resistant cases of orocutaneous and anal fistulae in patients on high-dose nicorandil therapy may be impossible without reduction or even withdrawal of nicorandil.

A 47-year-old man with neuro-Sweet syndrome in association with Crohn's disease: a case report

IntroductionSweets syndrome is a multi-system inflammatory disorder characterised by painful skin lesions and aseptic neutrophilic infiltration of various organs. We describe a case of Sweets syndrome with aseptic meningitis in association with Crohns disease (neuro-Sweet syndrome). This association has never been previously reported.Case presentationA 47-year-old Caucasian male with known Crohns disease presented with headache, fever and skin lesions resembling erythema nodosum. The cerebrospinal fluid revealed leukocyte pleocytosis and dominant neutrophils, but cultures were negative. A skin biopsy revealed neutrophilic dermatosis compatible with Sweets disease. The patient made a prompt recovery without the use of corticosteroids.ConclusionBecause of its multisystem nature, Sweets syndrome may present diagnostic difficulty to specialists. Correct diagnosis by skin biopsy will prompt appropriate treatment.

The Huntingdon Day Hospital Trial: secondary outcome measures

Objective: To compare day hospital to day centre rehabilitation using scales to measure mobility, activities of daily living and quality of life. Design: Single blind randomized controlled trial with home assessments at baseline (twice), six weeks and three months. Setting: Mainly rural health district. Day hospital and social services day centres in market towns. Interventions: Day hospital treatment or day centre rehabilitation by a physiotherapist and two health support workers. Main outcome measures: World Health Organization mobility scale scored with and without aid, Nottingham Extended Activities of Daily Living Scale and Nottingham Health Profile. Subjects: One hundred and five physically disabled older patients living at home referred for day hospital rehabilitation or maintenance before discharge from hospital (66) or referred as outpatients (39). Results: At three months there were no statistically significant differences between rehabilitation at day hospital and day centre for any of the outcome measurements. However, there were significant improvements between baseline and three months for the following subscales [mean change per six-week period (95% confidence interval)]: WHO mobility subscale (with aid) – 0.67 (–0.99,–0.35); Nottingham Health Profile mobility subscale –10 (–15.5,–4.5) Nottingham extended ADL mobility subscale +3.08 (1.78,4.37); Nottingham extended ADL leisure subscale +1.66 (0.96,2.36). Conclusion: There were no differences between day hospital and day centre in the outcomes measured. Day rehabilitation appeared to improve functional ability and mobility and scales reflecting these domains deserve further evaluation as outcome measures in this patient group. However, no improvement in quality of life was observed.