Paul W. Davies

Chlamydia pneumoniae Antibody Titers Are Significantly Associated With Acute Stroke and Transient Cerebral Ischemia : The West Birmingham Stroke Project

BACKGROUND AND PURPOSE Several studies have implied an association between Chlamydia pneumoniae and atherosclerosis. Our research was designed to investigate the association of this organism with strokes and transient cerebral ischemia. METHODS Antibodies to C pneumoniae were measured in 176 patients with stroke or transient cerebral ischemia and 1518 control subjects with noncardiovascular, nonpulmonary disorders. Acute infection or reinfection was defined by IgG > or =512 or IgM > or =8 or fourfold rise in IgG, and previous infection was defined by IgG 64 to 256 or IgA > or =8. Logistic regression was used to examine the influences of ethnic origin, age, sex, smoking habit, diabetes mellitus, steroid medication, and social deprivation on antibody levels. Some patients underwent CT and carotid ultrasound examinations and cholesterol, triglyceride, fibrinogen, and von Willebrand factor estimations. RESULTS We found that 13.6% of stroke/transient ischemic attack (TIA) patients and 5.7% of control subjects had antibody titers suggesting acute C pneumoniae (re)infection, while 32.4% of stroke/TIA patients and 12.7% of control subjects had titers suggesting previous infection (P<.05). Stroke/TIA patients differed from control subjects in their levels of acute and previous infection, with adjusted odds ratios of 4.2 (95% CI, 2.5 to 7.1) and 4.4 (95% CI, 3.0 to 6.5), respectively. These did not differ notably between strokes resulting from major nonhemorrhagic infarcts, small-vessel infarcts, or hemorrhage. Cholesterol, triglyceride, fibrinogen, and von Willebrand factor concentrations showed no apparent association with titers. CONCLUSIONS These data support the association of cerebral vascular disease with previous C pneumoniae infection and the association of stroke and transient cerebral ischemia with recrudescence of infection.

RELATION BETWEEN INITIAL BLOOD PRESSURE AND ITS FALL WITH TREATMENT

The relation between pre-treatment blood-pressure and the fall in pressure after treatment was examined for most classes of antihypertensive drugs. Positive correlations were demonstrated for all drugs, for placebo, and for bed rest. This suggests that for all manoeuvres response is related to the height of the pretreatment pressure. Substitution of the pre-treatment and achieved pressures by random numbers reveals that positive correlations are mathematically inevitable and do not indicate any action on a basic mechanism of essential hypertension. After statistical correction for mathematical associations between the variables the apparent effects were generally lost. A correlation between the pre-treatment value of any variable and its change after a therapeutic intervention thus may not be valid.

Chlamydia pneumoniae and asthma

BACKGROUND This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multiracial population, after adjustments for several potential confounding variables. METHODS Antibodies to C pneumoniaewere measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non-cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with “brittle” asthma. Acute infection or reinfection was defined by titres of IgG of ⩾512 or IgM ⩾8 or a fourfold rise in IgG, and previous infection by IgG 64–256 or IgA ⩾8. Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels. RESULTS Antibody titres consistent with acuteC pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection. These two groups did not differ significantly. However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97). CONCLUSIONS These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.

Counterion effects in a gold-catalyzed synthesis of pyrroles from alkynyl aziridines.

Aryl-substituted N-tosyl alkynyl aziridines undergo a gold-catalyzed ring expansion to afford 2,5-substituted pyrrole products. Under certain conditions, a ring-expansion and rearrangement leads to 2,4-substituted pyrroles. The reaction pathway is determined by the counterion to the gold catalyst.

Gold‐ or Platinum‐Catalyzed Synthesis of Sulfur Heterocycles: Access to Sulfur Ylides without Using Sacrificial Functionality

Sulfur ylides are potent reactive units which are utilized in synthetic chemistry for a variety of powerful carbon–carbon and carbon–heteroatom bond-forming reactions. The classical preparation of ylides depend on the use of “sacrificial functionality”: a leaving group is displaced by a sulfide with subsequent regioselective deprotonation of the resulting sulfonium salt [Eq. (1)]; or a sulfide is treated with a metal carbene, which is formed by the decomposition of a diazo compound with loss of molecular nitrogen [Eq. (2)]. The synthetic efficiency of such processes is also adversely affected by the manipulations required to introduce the precursor moiety. Consequently, the appeal of ylide chemistry is diminished by the negative implications of these strategies on reagent usage, waste production, and functional group tolerance.

Alkynes as masked ylides: Gold-catalysed intermolecular reactions of propargylic carboxylates with sulfides

The in situ-generation of sulfur ylides by the gold-catalysed rearrangement of propargylic carboxylates in the presence of sulfides has resulted in highly efficient and novel transformations.

Variation in cuff blood pressure in untreated outpatients with mild hypertension―Implications for initiating antihypertensive treatment

: Thirty-two patients with mildly elevated blood pressure (BP), but without target organ damage, attended a BP measuring clinic where duplicate BP measurements were made on 12 visits. During visits 1-3, BP showed a systematic decrease which varied from patient to patient. During visits 4-12, no further systematic changes in BP were observed. During the latter period, between-visit variation in BP was substantial, the standard deviation of the difference in BP from one visit to another being 10.4 mmHg for systolic, 6.8 mmHg for diastolic (phase IV) and 7.0 mmHg for diastolic (phase V). These values were used to determine the chance that the BP estimated after a number of visits differed from the average stable BP. After visit 4, the chance of a difference of 5 mmHg or more was 0.50 systolic blood pressure (SBP) and 0.32 diastolic blood pressure (DBP; phase V). Increasing the number of visits to six or more reduced the chance of error. Before initiating lifelong treatment in mild hypertensives free of target organ damage, BP should be recorded in duplicate on a minimum of six visits.

Chlamydia pneumoniae Antibodies in Severe Essential Hypertension

Several studies have implied an association between Chlamydia pneumoniae (C. pneumoniae) and cardiovascular disease. Our study was designed to determine whether this organism is associated with severe essential hypertension in a multiracial British population. Antibodies to C. pneumoniae were measured by microimmunofluorescence in 123 patients with chronic severe hypertension and 123 control subjects, matched for ethnic origin, age, sex, and smoking habit, admitted to the same hospital with various noncardiovascular, nonpulmonary disorders. Previous infection was defined by IgG 64 to 256, provided that there was no detectable IgM. Multiple regression analyses of matched and unmatched data were used to investigate the influences of antibody levels and potential confounding factors (ethnic origin, age, sex, smoking habit, diabetes mellitus, and social deprivation) on hypertension. A portion of the hypertensive patients underwent echocardiography, estimation of left ventricular mass index, and measurements of fibrinogen, D-dimer, and von Willebrand factor concentrations. Thirty-five percent of hypertensive patients and 17.9% of matched control subjects had antibody titers consistent with previous C. pneumoniae infection. The hypertensive patients differed significantly from their matched control subjects in their level of previous infection, with an odds ratio of 2.5 (95% confidence interval, 1.3 to 4.7). There were no significant differences in antibody levels between patients with left ventricular hypertrophy and those without it. Fibrinogen, D-dimer, and von Willebrand factor concentrations were not significantly associated with antibody levels. These data support an association of C. pneumoniae with severe essential hypertension. They provide no evidence of a predisposition to develop left ventricular hypertrophy in hypertensive patients with C. pneumoniae infection or of associations with hypercoagulability or endothelial dysfunction.

Paracetamol induced hepatotoxicity

Aim: To identify the clinical and biochemical risk factors associated with outcome of paracetamol induced significant hepatotoxicity in children. Methods: Retrospective case notes review of those with paracetamol overdose admitted from 1992 to 2002. Patients were analysed in two groups: group I recovered after conservative treatment and group II developed progressive liver dysfunction and were listed for liver transplantation. Results: Of 51 patients (6 males, 45 females, aged 0.8–16.1 years), 6 (aged <7 years) received cumulative multiple doses, and 45 a single large overdose (median 345 mg/kg, range 91–645). The median (range) interval to hospital at presentation post-ingestion was 24 hours (4–65) and 44 hours (24–96) respectively in groups I and II. Patients received standard supportive treatment including N-acetylcysteine. All children in group I survived. In group II, 6/11 underwent orthotopic liver transplantation (OLT) and 2/6 survived; 5/11 died awaiting OLT. Cerebral oedema was the main cause of death. Children who presented late to hospital for treatment and those with progressive hepatotoxicity with prothrombin time >100 seconds, hypoglycaemia, serum creatinine >200 μmol/l, acidosis (pH <7.3), and who developed encephalopathy grade III, had a poor prognosis or died. Although hepatic transaminase levels were markedly raised in both groups, there was no correlation with necessity for liver transplantation or death. Conclusion: Accidental or incidental paracetamol overdose in children may be associated with toxic liver damage leading to fulminant liver failure. Delayed presentation and/or delay in treatment, and hepatic encephalopathy ⩾grade III were significant risk factors, implying poor prognosis and need for OLT. Prompt identification of high risk patients, referral to a specialised unit for management, and consideration for liver transplantation is essential.

A longitudinal study of cardiovascular dynamic changes throughout pregnancy

Abstract Systemic blood pressure (measured with a zero-randomized sphygmomanometer), stroke volume and heart-rate (measured with a Minnesota Impedance Cardiograph), hematocrit, and their derivatives — cardiac output and peripheral vascular resistance — have been assessed in three groups of subjects. First, a control group of 19 nonpregnant women were matched for age and weight with the subjects in the second group, which consisted of 19 patients who were seen at regular intervals on 12 to 15 occasions from 8 to 11 wk of pregnancy until 6 wk postpartum. The third group consisted of 8 patients seen from before conception, throughout pregnancy and to several months postpartum. Readings were made with the subject in each of six positions: supine, reclining, left and right lateral, left and right tilt. This paper concerns the readings obtained in the left lateral position. The data showed that pulse rate rose throughout pregnancy. Stroke volume and cardiac output rose shortly after conception, the increase over the prepregnancy level being statistically significant by 12 wk. Thereafter both values fell throughout the rest of pregnancy and were below prepregnancy levels by about term, taking some weeks to regain the prepregnancy value. There were irregular fluctuations in the level of systolic blood pressure; diastolic blood pressure fell during the first 16 wk and then rose to reach almost the prepregnancy value by term. Peripheral resistance fell during the first trimester, then increased markedly throughout the remainder of pregnancy.