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Biomedical subjects

C L French

Publications and source records attributed to C L French.

10 recordsLinked to original sources
PubMed1998

From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults.

BACKGROUND: Cough is the most common complaint for which adults see a physician in the ambulatory setting in the United States. An anatomical diagnostic protocol has been used since 1981 to evaluate patients with chronic cough. It has been shown to be effective in diagnosing the cause of cough and leading to specific treatment in a variety of adult populations but has never been evaluated specifically in a population of older adults. OBJECTIVES: To question whether the spectrum and frequency of causes of chronic cough and the response to therapy would be different in older adults. METHODS: Thirty patients at least 64 years of age with a history of cough lasting at least 3 weeks were prospectively evaluated with a protocol designed to detect diseases that stimulate the afferent limb of the cough reflex. The final diagnosis of the cause of chronic cough required fulfillment of pretreatment criteria and having cough disappear with specific therapy. When more than one disease fulfilled pretreatment diagnostic criteria, therapy was instituted in the order that these were fulfilled. Probability statistics were used to describe the testing characteristics of individual components of the diagnostic protocol in terms of sensitivity, specificity, positive predictive value, and negative predictive value as they applied to chronic cough. RESULTS: Forty causes of chronic cough were identified in all 30 patients. Postnasal drip syndrome, gastroesophageal reflux disease, and asthma were the most common causes of chronic cough, accounting for 85% of all causes found. Among patients with normal chest radiograph findings who were not cigarette smokers and not taking an angiotensin-converting enzyme inhibitor, postnasal drip syndrome, gastroesophageal reflux disease, and asthma accounted for 100% of all causes found. Specific therapy was successful in eliminating chronic cough in 100% of the patients studied. Except for barium esophagography, all laboratory tests for which information was available had sensitivities and negative predictive values of 100%. CONCLUSIONS: Postnasal drip syndrome, gastroesophageal reflux disease, and asthma accounted for 85% of all causes of chronic cough in older adults. Chronic cough caused substantial physical and emotional morbidity among older patients. The major value of performing objective testing in evaluating chronic cough is its ability to rule out specific diseases as a diagnostic possibility. The following clinical profile consistently predicts patients with cough attributable to gastroesophageal reflux disease: the patient has cough that has been persistently troublesome for at least 3 weeks; does not smoke cigarettes; does not take an angiotensin-converting enzyme inhibitor; does not have or has not responded to therapy for postnasal drip syndrome and asthma; and has normal or nearly normal findings and stable chest radiograph. The differences between what we observed regarding chronic cough in older adults and observations by ourselves and others regarding chronic cough in general are minor.

Aged↗
PubMed1993

Difficult-to-control asthma. Contributing factors and outcome of a systematic management protocol.

To our knowledge, there are no published results of protocols for managing difficult to control asthma (DTCA) or of the spectrum and frequencies of reasons why asthma can be difficult to control (DTC). To assess the usefulness of a systematic management protocol and determine the reason(s) why asthmatics are DTC, we developed a protocol that systematically considered multiple factors that may make asthma worse and prospectively evaluated the outcomes of therapeutic interventions for these factors and of inhaled corticosteroids (ICS) and azathioprine. We studied 42 consecutive and unselected DTCAs (19 men and 23 women) whose age was 48 +/- 15.9 years. They had a diagnosis of asthma for 15.1 +/- 15.8 years, were DTC for 4.8 +/- 7.8 years, and were followed up by us in the study for a total of 3.5 +/- 1.9 years. Initially, the dose of prednisone was 30.2 +/- 22 mg/d. Following utilization of the protocol, 74 percent were no longer DTC. It took 1.8 +/- 1.7 years for them to no longer be DTC; they remained so for 1.8 +/- 1.5 years. In these patients, 2.7 +/- 1.2 factors appeared to be responsible for the DTC state; 80 percent had > or = 2. Improvement was more likely if gastroesophageal reflux (GER) was a factor (p = 0.014); it correlated with the addition of ICS (p = 0.04) and treatment for GER (p = 0.02). Failure to reverse DTCA correlated with the suspicion (p = 0.004) and admission of nonadherence (p = 0.04). In 14 patients given azathioprine, prednisone dose decreased from 45 +/- 25.3 to 13.3 +/- 21.6 mg/d (p = 0.003); 6 of 14 achieved no longer DTC status; and substantial morbidity occurred. The reason(s) for DTCA could be determined in most instances by utilizing a systematic protocol; multiple factors were responsible in the majority of cases; treatment for GER and ICS were the two most helpful interventions; nonadherence was the most likely reason suspected for maintaining DTCA; and azathioprine acted as a corticosteroid-sparing agent that should not be prescribed routinely.

Adolescent↗
PubMed1993

Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects.

BACKGROUND: Gastroesophageal reflux (GER) is a common cause of chronic cough. Moreover, chronic cough can be the sole presenting manifestation of GER disease (GERD). It has been suggested recently that GER most often causes chronic cough by stimulating the distal esophagus. To gain further diagnostic and pathophysiologic knowledge, we prospectively evaluated a group of patients with chronic cough likely to be due to GER with extensive gastrointestinal and respiratory studies and then observed their response to antireflux therapy. METHODS: We prospectively characterized 12 subjects whose chronic cough was likely to be due to GER by chest radiographs, barium esophagography, 24-h esophageal pH monitoring (EPM) with probes in the distal and proximal esophagus, esophagoscopy, and bronchoscopy. Then, prior to instituting antireflux therapy, we objectively counted coughs during the distal esophageal infusion of 0.1 N HCl or 0.9 percent saline solution administered in a randomized, double-blind, standardized fashion (ie, Bernstein acid-perfusion test). RESULTS: Gastroesophageal reflux was determined to cause cough in all subjects based on disappearance of cough with antireflux therapy. It was clinically "silent" in 75 percent. The EPM was the test most frequently abnormal (sensitivity, 92 percent). Distal esophageal data revealed that 10 of 12 subjects had GER-induced coughs (12 +/- 12) while only 7 of 12 had an abnormal esophageal pH conventional parameter (eg, percent time pH < 4). Compared with the distal esophagus, GER to the proximal esophagus occurred (p = 0.017) and induced cough (p = 0.004) less often. Compared with baseline (9.3 +/- 17.6), there were no differences in coughs induced by the infusion of saline solution (9.2 +/- 15.9) or acid (15.1 +/- 26.7); the number of coughs induced by acid was negatively correlated with distal esophageal acid-GER events during EPM (r = -0.64, p = 0.01). Neither bronchoscopy nor chest radiographs were consistent with aspiration. CONCLUSIONS: There is a clinical profile that prospectively predicts which patients have chronic cough due to GER. The cough was most likely due to stimulation of the distal esophagus, not aspiration. Intraesophageal acid is unlikely to be the sole mediator in gastric juice causing the cough. While EPM is the single most helpful diagnostic test, conventionally utilized diagnostic indices of GERD can be misleadingly normal; observing GER-induced coughs is more frequently helpful.

Adult↗
PubMed1990

Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.

A successful, systematic, anatomic, diagnostic protocol for evaluating patients with chronic cough was presented in 1981. To determine whether it was still valid, we prospectively evaluated, over a 22-month interval, 102 consecutive and unselected immunocompetent patients complaining of cough an average of 53 +/- 97 months (range, 3 wk to 50 yr). Utilizing the anatomic, diagnostic protocol modified to include prolonged esophageal pH monitoring (EPM), the causes of cough were determined in 101 of 102 (99%) patients, leading to specific therapy that was successful in 98%. Cough was due to one condition in 73%, two in 23%, and three in 3%. Postnasal drip syndrome was a cause 41% of the time, asthma 24%, gastroesophageal reflux (GER) 21%, chronic bronchitis 5%, bronchiectasis 4%, and miscellaneous conditions 5%. Cough was the sole presenting manifestation of asthma and GER 28 and 43% of the time, respectively. While history, physical examination, methacholine inhalational challenge (MIC), and EPM yielded the most frequent true positive results, MIC was falsely positive 22% of the time in predicting that asthma was the cause of cough. Laboratory testing was particularly useful in ruling out suspected possibilities. We conclude that the anatomic diagnostic protocol is still valid and that it has well-defined strengths and limitations.

Adolescent↗
PubMed1989

Chronic cough as the sole presenting manifestation of gastroesophageal reflux.

Nine patients complaining only of chronic cough of unknown cause were prospectively studied with prolonged esophageal pH monitoring (EPM) before and after cough had disappeared as a complaint in order to determine if and why gastroesophageal reflux (GER) was causing their coughs. Coughs disappeared as a complaint an average of 161 +/- 75 days after medical therapy for GER. Comparisons of pretreatment and post-treatment EPM data revealed the following: numbers of coughs (p = 0.029), total refluxes (p = 0.001), refluxes greater than or equal to 5 min (p = 0.019), and reflux-induced coughs (p = 0.005) had significantly decreased in the distal esophagus, and total refluxes (p = 0.05) had significantly decreased in the proximal esophagus. During the entire study period, the number of coughs were significantly correlated with the number of total refluxes (p = 0.039), longest reflux (p = 0.019), number of refluxes greater than or equal to 5 min (p = 0.006), and percent of total time that pH was less than 4 (p = 0.017) in the distal esophagus. On the basis of these results, we conclude that (1) cough can be the sole presenting manifestation of GER, and it gradually responds to standard GER therapy; (2) prolonged EPM is safe, well-tolerated, and extremely useful in diagnosing clinically silent GER; (3) the mechanism by which GER causes cough is related to a critical number and/or duration of reflux episodes in the distal and/or proximal esophagus.

Adult↗
PubMed1988

Evidence that the functional beta-actin gene is single copy in most mice and is associated with 5' sequences capable of conferring serum- and cycloheximide-dependent regulation.

Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of this gene were shown to confer serum-inducible expression upon a heterologous reporter gene when transfected into mouse fibroblasts. Moreover, these sequences rendered reporter gene expression superinducible by a combination of serum and cycloheximide. These experiments indicate that the 5' end of the mouse beta-actin gene contains sequence elements which mediate the stimulatory effects of serum growth factors and which are responsive to both positive and negative regulators of gene expression.

Acetyltransferases↗
PubMedDate not supplied

Impact of chronic cough on quality of life.

BACKGROUND: Cough is the most common complaint for which adult patients seek medical care in the United States; however, the reason(s) for this is unknown. OBJECTIVES: To determine whether chronic cough was associated with adverse psychosocial or physical effects on the quality of life and whether the elimination of chronic cough with specific therapy improved these adverse effects. METHODS: The study design was a prospective before-and-after intervention trial with patients serving as their own controls. Study subjects were a convenience sample of 39 consecutive and unselected adult patients referred for evaluation and management of a chronic, persistently troublesome cough. Baseline data were available for 39 patients and follow-up for 28 patients (22 women and 6 men). At baseline, demographic, Adverse Cough Outcome Survey (ACOS), and Sickness Impact Profile (SIP) data were collected and patients were managed according to a validated, systematic protocol. Following specific therapy for cough, ACOS and SIP instruments were readministered. RESULTS: The ages, sex, duration, and spectra and frequencies of the causes of cough were similar to multiple other studies. At baseline, patients reported a mean +/- SD of 8.6 +/- 4.8 types of adverse occurrences related to cough. There were significant correlations between multiple ACOS items and total, physical, and psychosocial SIP scores. Psychosocial score correlated with total number of symptoms (P<.02). After cough disappeared with treatment, ACOS complaints decreased to a mean +/- SD of 1.9 +/- 3.2 (P<.0001) as did total (mean +/- SD, 4.8 +/- 4.5 to 1.8 +/- 2.2) (P= .004), psychosocial (mean +/- SD, 4.2 +/- 6.8 to 0.8 +/- 2.3) (P = .004), and physical (mean +/- SD, 2.2 +/- 2.9 to 0.9 +/- 1.8) (P = .05) SIP scores. Multiple linear regression analysis showed that 54% of variability of the psychosocial SIP score was explained by 4 ACOS items while none of the physical score was explained. CONCLUSIONS: Chronic cough was associated with deterioration in patients' quality of life. The health-related dysfunction was most likely psychosocial. The ACOS and SIP appear to be valid tools in assessing the impact of chronic cough.

Chronic Disease↗
PubMedDate not supplied

Potency ranking of methemoglobin-forming agents.

This study represents the first systematic attempt to rank methemoglobin-forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose-response data for comparative purposes. Six agents that are direct-acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to least potent inducers of the bioactivated agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent-specific sensitivities are addressed.

Analysis of Variance↗