Wartime mosquito-eradication effort in World War II was turned into what is today the Centers for Disease Control.
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Centers for Disease Control and Prevention, U.S.↗
Biomedical subjects
G Reynolds
Publications and source records attributed to G Reynolds.
Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas.
We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV-positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies.
Adenocarcinoma↗
Statistics and clinical trials.
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Clinical Trials as Topic↗
Recurrence of ectopic pregnancy: the role of salpingitis.
We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk.
Adult↗
Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.
1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in the seven extensive metabolisers and 8 ml min-1 in the poor metaboliser; to norcodeine the values were 103 +/- 33 ml min-1 and 90 ml min-1; to codeine-6-glucuronide the values were 914 +/- 129 ml min-1 and 971 ml min-1; and intrinsic clearance was 1568 +/- 103 ml min-1 and 1450 ml min-1. These values were not significantly (P greater than 0.05) altered by chronic administration.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Haemodynamic and radionuclide effects of amlodipine in coronary artery disease.
1. The haemodynamic and radionuclide effects of a new long-acting slow-calcium channel blocking agent, amlodipine, were evaluated in 32 patients with coronary artery disease. 2. Haemodynamic measurements in 24 patients were made at rest and 10 to 15 min after 20 mg i.v. amlodipine. Amlodipine significantly reduced systemic arterial blood pressure and vascular resistance index with an increased heart rate and augmented cardiac index. Cardiac stroke volume index rose and stroke work fell without change in pulmonary artery occluded pressure (PAOP). 3. The exercise effects were determined by comparison of measurements during 4 min of supine bicycle exercise at a fixed workload before and after drug treatment. During dynamic exercise, amlodipine reduced systemic arterial pressure and vascular resistance index. Exercise cardiac index, stroke volume index and heart rate were higher. The left ventricular filling pressure was significantly reduced. 4. Radionuclide parameters were studied in 16 patients at rest and on exercise; ejection fraction was unaltered following amlodipine. 5. Pre-therapy haemodynamic values correlated with response following amlodipine for resting mean blood pressure, systemic vascular resistance and exercise PAOP. 6. Thus, the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and thereby improve cardiac pumping performance.
Adult↗
Diffuse Lewy body disease: the clinical features.
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Aged↗
Direct determination of codeine-6-glucuronide in plasma and urine using solid-phase extraction and high-performance liquid chromatography with fluorescence detection.
A sensitive and selective method was developed for the direct determination of codeine-6-glucuronide in plasma and urine using high-performance liquid chromatography (HPLC) with fluorescence detection. Codeine-6-glucuronide was synthesised and its purity estimated using acid and enzyme hydrolysis. The hydrolysis of codeine-6-glucuronide by beta-glucuronidase was incomplete and urine reduced the extent of hydrolysis. Codeine-6-glucuronide was recovered from plasma using a solid-phase extraction column and separated on a reversed-phase C18 HPLC column. The assay showed good reproducibility and accuracy (within 10%), and standard curves were linear between 32 and 1600 ng/ml in plasma and between 0.32 and 160 micrograms/ml in urine. The assay has been applied to the study of the pharmacokinetics and metabolism of codeine in patients.
Chromatography, High Pressure Liquid↗
A time series analysis of gonorrhea surveillance data.
Gonorrhea is the most frequently reported communicable disease in the United States. In response to rapidly rising rates in the late 1960s, the Public Health Service instituted a gonorrhea control programme. An important component of the programme is the screening of women for gonococcal infections. We use a time series intervention model to estimate the initial increase in reporting of cases in women associated with the control programme. From the middle 1970s to the middle 1980s, a regular seasonal pattern in the data is conspicuous. We use a second time series model to quantify the seasonal variation during this period and to construct forecasts.
Data Interpretation, Statistical↗
Comparative effects of atenolol and cicloprolol on cardiac performance in coronary heart disease.
Cicloprolol is a new cardioselective beta-blocking agent with partial agonist activity (intrinsic sympathomimetic activity, ISA). Its haemodynamic profile was compared with that of atenolol (cardioselective; no ISA) in a comparative dose-response study of 24 ischaemic patients with diminished cardiac reserve. Following a stable control period, equivalent intravenous (i.v.) beta-blocking boluses of atenolol (1, 1, 2, and 4 mg) or cicloprolol (0.025, 0.025, 0.05, and 0.1 mg/kg) were randomly administered and haemodynamics and left ventricular ejection fraction were determined at rest and during bicycle exercise. At rest, atenolol reduced heart rate (HR) and cardiac index; diastolic blood pressure (DBP), systemic vascular resistance index (SVRI), and pulmonary artery occluded pressure (PAOP) increased without change in mean arterial pressure (MAP). Cicloprolol increased left ventricular ejection fraction, reduced its end-diastolic volume, and tended to reduce filling pressure without change in other variables. During exercise, atenolol reduced ejection fraction and increased SVRI; in contrast, cicloprolol did not significantly alter these parameters. Attenuation of exercise tachycardia and cardiac index increase was similar after each agent. Thus, the cardiac performance assessed from left ventricular stroke index or ejection fraction/filling pressure relationships was less depressed after cicloprolol as compared with atenolol. The relevance of such haemodynamic differences to exercise ability or quality of life during sustained therapy warrants examination.
Adrenergic beta-Antagonists↗
Human maximization test of falcarinol, the principal contact allergen of English ivy and Algerian ivy (Hedera helix, H. canariensis).
In a human maximization test of 5% falcarinol isolated from Hedera helix, 10 of 20 subjects were sensitized. No subjects gave irritant reactions to 5%, 10 became sensitive to 1%, and 7 to 0.05%, with 3 of these giving 3+ to 4+ bullous reactions.
Alkynes↗
Transplantation: the future.
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Forecasting↗
Neurogenic true hypertrophy of one calf and atrophy of the other.
Unilateral calf hypertrophy has been described in association with a variety of conditions. Bilateral neurogenic leg weakness with muscle wasting on one side and true hypertrophy on the other, however, has rarely been described. We report a 37-year-old heroin and alcohol abuser with a three-year history of weakness of the left leg and progressive enlargement of the right calf. Computed tomography of the right calf confirmed the presence of true hypertrophy. Electromyography showed denervation in the muscles of both legs. Nerve conduction studies were indicative of peripheral neuropathy. Biopsy of the gastrocnemius muscles revealed the presence of neurogenic atrophy on both sides, with marked hypertrophy and splitting of individual muscle fibers on the right. To our knowledge, this is only the second recorded case showing both muscle atrophy and muscle hypertrophy in response to denervation.
Adult↗
A disorder of cortical GABAergic innervation in Alzheimer's disease.
Synaptosomal gamma-aminobutyric acid (GABA) uptake has been used as a biochemical marker for GABAergic terminals in controls and Alzheimer disease brains. Use of this marker suggests a large (ca. 70%) loss of cortical and hippocampal GABA terminals in Alzheimer brain. To explain this observation we suggest that neuron loss in this disorder occurs via a process of cortical retrograde degeneration. This scheme reconciles our findings with previous neurochemical measurements on Alzheimer disease brains and also better reconciles the biochemistry with the histology of the disorder.
Aged↗
Region-specific loss of glutamate innervation in Alzheimer's disease.
Synaptosomal D-aspartate has been used as a marker for glutamate neurons in control and in postmortem Alzheimer's disease brains. This technique shows a marked (60%) decrease of the glutamate uptake site in cortical and hippocampal regions. There were no significant changes in subcortical regions. We interpret these results as indicating loss of, or damage to, cortical glutamatergic innervation. These losses probably represent the biochemical correlate of pyramidal neuron damage in Alzheimer's disease.
Alzheimer Disease↗
Haemodynamic dose-response actions of cicloprolol in left ventricular dysfunction due to ischaemic heart disease.
Cicloprolol is a cardioselective beta-1 partial agonist; its haemodynamic and radionuclide (nuclear stethoscope) effects were determined in 22 patients with impaired left ventricular function due to coronary artery disease. Following a 20 min stable control period, the effects of four doses of cicloprolol (0.025, 0.025, 0.05 and 0.1 mg/kg at 10 min intervals) were measured at rest 5-10 min after each intravenous injection. The effects of the cumulative 0.2 mg/kg dosage were assessed during supine bicycle exercise and compared with a control exercise period. At rest there were significant increases in systolic arterial without change in mean blood pressure. The heart rate and cardiac index were unchanged. There was a significant increase in left ventricular ejection fraction with a reduction in filling pressure and volume. Patients with resting heart rate below 75 beats/min and with ejection fraction greater than 35% showed the greatest improvement. During supine bicycle exercise, ejection fraction was increased compared to control (31 +/- 2 to 36 +/- 2; P less than 0.01), cardiac volume reduced and exercise tachycardia attenuated. These data suggest that cicloprolol may be of value where beta-blockade is considered in the presence of underlying left ventricular dysfunction due to ischaemic heart disease.
Adrenergic beta-Antagonists↗
Comparative hemodynamic dose-response effects of five slow calcium channel-blocking agents in coronary artery disease.
A prospective, randomized study compared the hemodynamic effects of equivalent doses of five slow calcium channel blockers (verapamil, diltiazem, nicardipine, nisoldipine, and amlodipine) in 50 patients with ischemia. After a stable control period, dose-response curves were constructed for each drug with hemodynamics measured 10 minutes after intravenous boluses. Each drug reduced mean systemic arterial pressure (P less than 0.01) and systemic vascular resistance index (P less than 0.01). The heart rate increased after nicardipine, nisoldipine, and amlodipine (P less than 0.01) but was unchanged after verapamil and reduced after diltiazem (P less than 0.01). The left ventricular filling pressure increased after amlodipine (P less than 0.05) and verapamil (P less than 0.01) but was unchanged with the other compounds. Cardiac index increased substantially after the dihydropyridines (P less than 0.01), with little change after verapamil or diltiazem. Cardiac double product fell only after verapamil and diltiazem. These studies provide quantitation of the comparative actions of acute intravenous calcium channel blockade in coronary disease.
Amlodipine↗