DNA flow cytometry as a surrogate end-point in patients with superficial bladder cancer treated with 4-HPR.
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Adult↗
Biomedical subjects
M Costantini
Publications and source records attributed to M Costantini.
The effect of symptoms and nonspecific motility abnormalities on outcomes of surgical therapy for gastroesophageal reflux disease.
The outcome of Nissen fundoplication in patients with a nonspecific motility abnormality compared with the outcome in patients with normal motility is unknown. One hundred consecutive patients who underwent primary Nissen fundoplication were evaluated before and a median of 50 months after operation, with emphasis on the presence of a preoperative motility disorder and its relationship to preoperative and postoperative symptoms. Compared with patients who had normal motility, patients with a nonspecific motility abnormality had a greater prevalence and severity of heartburn and regurgitation before operation. These patients also had a greater esophageal exposure to gastric juice on pH monitoring as a result of poorer esophageal clearance function. The prevalence and severity of preoperative dysphagia was not related to the presence of a motility disorder. A 90% or a 95% actuarial success rate was achieved in the relief of heartburn and regurgitation over a 96-month period in patients with and without a motility abnormality. The overall actuarial success rate was 93%. Dysphagia was rarely caused or made more severe by the procedure; if present before the operation, it was relieved in most patients. The prevalence of persistent postoperative dysphagia was similar in patients with and without a motility abnormality. The success of Nissen fundoplication in properly selected patients is not affected by the presence of a nonspecific motility disorder.
Deglutition Disorders↗
Altered esophageal pain threshold in irritable bowel syndrome.
Gut motility disorders and altered pain perception were reported in patients with irritable bowel syndrome (IBS). To verify foregut involvement in IBS, we studied 30 patients using esophageal manometry and 24-hr pH monitoring of the distal esophagus. Two subgroups of patients underwent esophageal provocative tests (bethanechol 50 micrograms/kg subcutaneously and esophageal balloon distension test). Twelve healthy volunteers formed a control group. A pain threshold on esophageal distension significantly lower than in healthy subjects (11.5 +/- 1 ml vs 22.2 +/- 1.7 ml, P < 0.01) was found in IBS patients. On the other hand, no differences between patients and controls were detected in lower esophageal sphincter pressure and length, esophageal body motility, or GER pattern; furthermore, bethanechol stimulation elicited similar esophageal body motility changes. Our study could confirm no detectable basal or bethanechol-induced esophageal motility disorders in IBS patients, nor enhanced GER. Esophageal involvement in IBS consists of a lower pain threshold on esophageal distension, possibly reflecting an altered visceral receptor sensitivity or modulation throughout the gut.
Adult↗
Pharyngeal swallowing. The major factor in clearance of esophageal reflux episodes.
OBJECTIVE: This study defined the clearance mechanisms of naturally occurring reflux episodes in normal subjects and patients with gastroesophageal reflux disease. SUMMARY BACKGROUND: Previous studies on acid clearance have been performed in the laboratory setting in supine subjects using acid instillation and stationary motility. The mechanisms of clearance have not been studied using ambulatory pH and motility monitoring. METHODS: A new system capable of monitoring simultaneously for 24 hours pharyngeal pressure, esophageal motility, and pH was used to study the clearance of naturally occurring reflux episodes in 10 normal subjects and 18 patients with gastroesophageal reflux disease. Esophageal contraction waves were classified as primary (i.e., initiated by a pharyngeal swallow) and secondary (i.e., unrelated to a pharyngeal swallow). RESULTS: A total of 1288 reflux episodes were analyzed, during which 2781 contraction waves occurred. Clearance (i.e., restoration of pH to > 4) occurred after primary peristalsis in 83% of reflux episodes. An additional 11% were cleared by pharyngeal swallows without an esophageal body response. Secondary waves were rare and when they occurred, only 19% were peristaltic. Secondary peristalsis cleared only 9 of the 1288 reflux episodes. Patients and normal subjects cleared reflux episodes similarly. Baseline swallowing frequency was 0.87/min during the daytime and increased to 2.59/min (p < 0.01) during daytime reflux episodes. Swallowing frequency in response to nighttime reflux episodes was less (1.42/min; p < 0.05). CONCLUSIONS: Pharyngeal swallowing is the most important mechanism for esophageal acid clearance. Secondary waves are rare, usually disorganized, and unimportant in clearing a reflux episode. During sleep, the mechanisms of clearance are depressed.
Adolescent↗
Palliative home care and place of death among cancer patients: a population-based study.
This population-based study of all cancer deaths (n = 12,343) occurring in Genoa, Italy, from 1986 to 1990 investigated the relation between place of death and age, sex, marital status, education, cancer site and provision of palliative home care (PHC). The proportion of home deaths significantly increased from 27.9% (1986) to 33.0% (1990) and was twice as frequent among PHC users (60.8%) than among nonusers (29.3%). The number of patients dying of cancer who received PHC increased from 41 in 1986 (1.6% of cancer deaths) to 191 in 1990 (8.0% of cancer deaths). PHC users, when compared to nonusers were younger, more frequently married, had a higher level of education and were more frequently affected by cancers of the lung, breast or prostate. Multivariate analysis shows that the probability of home death increased with increasing age and education level and was higher in females and in married patients. The provision of PHC was the strongest predictor of home death (OR = 4.00; 95% CI = 3.33-4.81), while the temporal trend almost disappeared. These results suggest that most of the increase in home deaths from 1986 to 1990 is attributable to the PHC and that expansion of the PHC services may enable about 60% of cancer patients to die at home. These results appear to be desirable from the individual patient's viewpoint and in a public health perspective.
Age Factors↗
[Coma: a new humanistic discipline].
Two researches merge together in this article: the former originates in coma clinical practice and aims at reaching a more abstract formulation, while the latter originates in the theory of narrative and tries to find practical applications. The interest of this merger lies in opening up a new field of study, comatics, whose object is to conceive the best possible conditions for comatose people, for specific varieties of comatose people and even for this or that individual comatose person to fit back into social life, which involves grasping meaning and clues and signals and signs, and finding one's way about in the circuit of communication. Comatics, in short, is semiotics as applied to awakening from comatose states.
Coma↗
Value of physiologic assessment of foregut symptoms in a surgical practice.
BACKGROUND: The aim of this study was to evaluate the reliability of symptoms in the diagnosis of gastroesophageal reflux disease and esophageal motility disorders as assessed by functional tests. METHODS: In 365 patients referred for suspected esophageal functional disease, symptomatic assessment was compared with the results of esophageal manometry and ambulatory 24-hour pH monitoring of the distal esophagus. RESULTS: Based on the patients' chief complaint, the symptomatic diagnosis was gastroesophageal reflux (44%), esophageal motor disorder (26%), chest pain of esophageal origin (9%), reflux and aspiration (8%), and abdominal pathology (12%). The symptomatic diagnosis was considerably altered by the results of the esophageal function tests: gastroesophageal reflux and motility disorders were found in all symptomatic diagnostic groups and a large number of patients in each group tested normal. The sensitivity and specificity of symptom-based diagnoses for functional disease were low. CONCLUSIONS: The results of this study showed that symptoms are an unreliable guide of esophageal abnormality, illustrating the need for objective testing in these patients, particularly to avoid inappropriate medical or surgical therapy.
Adolescent↗
Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast.
The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts greater than 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by the K+/Na+ ratio in BCF, and the risk of breast cancer. The inverse relationship between K+ and Na+ and the bimodal distribution of the K+/Na+ ratio in BCF were confirmed. Type I cysts were defined as cysts with a K+/Na+ greater than 1.5 in BCF. Among women with type I cysts, a higher proportion of women with one or no births, of women with a history of apocrine cysts, of current smokers, and of women who do not drink coffee was found, as compared to women with other types of cysts. The risk of cyst relapse was significantly higher among women with type I cysts than among women with other types of cysts and among women with multiple cysts at presentation. These findings indicate that type I BCF is a marker of "active" gross cystic disease of the breast and suggest that it may be associated with increased breast cancer risk.
Abortion, Spontaneous↗
Oesophagitis and pH of refluxate: an experimental and clinical study.
This experimental and clinical study examined the relationship between oesophageal damage and optimal pH of refluxate, and whether 24-h pH monitoring at optimal pH could discriminate the severity of oesophagitis. The rabbit oesophagus was perfused in vivo with pepsin and hydrochloric acid solutions of differing pH for 60 min. Maximal oesophageal damage coincided with peptic solutions at pH 1.5-2.5. Fifty-nine patients with proven gastro-oesophageal reflux disorders were tested for manometric features of the lower oesophageal sphincter (pressure, overall length and abdominal length) and oesophageal exposure to different pH levels. They were classified into four groups according to the endoscopically demonstrated severity of oesophagitis. Supine exposure at the optimal pH level for pepsin activity (pH 1.5-2.5) and overall sphincter length were found to discriminate the severity of oesophagitis reliably in 75 per cent of cases.
Adolescent↗
Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint.
The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (+/- SE) S-phase and G2+M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 +/- 4.1% to 7.5 +/- 3.3% and 10.3 +/- 2.2% to 5.2 +/- 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 +/- 3.4% to 12.4 +/- 2.7% and 9.8 +/- 1.6% to 12.6 +/- 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Chemotherapy-induced amenorrhea and other clinical and pathological parameters in the prognosis of breast cancer patients.
147 stage II pre- and perimenopausal breast cancer patients were treated with cyclophosphamide-methotrexate-5-fluorouracil (CMF)- based adjuvant regimens. 103 (72%) patients became amenorrheic during or immediately after the end of the chemotherapy program. Univariate analyses for age, menstrual status, nodal involvement, grading, estrogen and progesterone receptor status indicated no correlation between induction of amenorrhea and a significant prolongation of overall and disease-free survival. Multivariate analyses confirmed that young age at diagnosis, increasing number of infiltrated nodes, negative progesterone receptor status and grade 3 tumors are associated with a worse prognosis. Our results suggest that no benefit is expected in women with drug induced amenorrhea after CMF adjuvant treatment.
Adult↗
Univariate and multivariate analyses of the relationship between adenocarcinoma and solitary and multiple adenomas in colorectal adenoma patients.
In 584 consecutive patients with no previous history of cancer or polypectomy, 769 adenomas were excised endoscopically and classified retrospectively according to the following parameters: macroscopic growth pattern, size, histological type, grade of dysplasia, anatomical site, presence of adenocarcinoma (ADK), number of adenomas and sex and age of the patient. A multivariate logistic analysis confirmed that size and histological type are the 2 most important predictors of ADK, both in solitary and in multiple adenomas. Adenomas located in the sigmoid portion and in the rectum have an increased probability of ADK, independent of size and histology. Multiple polyps, when compared to solitary polyps, were more frequent in males (p less than 0.01) and were more often larger than 2 cm. Significant similarities in histology, morphology and degree of dysplasia were observed among multiple adenomas from the same patient.
Adenocarcinoma↗
[Esophageal manometry and pH-monitoring: cost-benefit analysis].
Functional tests of the esophagus have become increasingly popular over the last 10 years. Here we present a cost/benefit analysis model to evaluate the real contribution to diagnosis with reference to the cost of these tests. All of the patients referred to the digestive physiopathology laboratory at the Institute of Surgical Semiotics, from 1988 to 1990, were evaluated for gastroesophageal reflux disease (152 cases), dysphagia (27 cases) and chest pain (12 cases). The cost of each modified diagnosis was L. 508,250 in the first case, L. 315,772 in the second case and L. 262,446 in the third case. Additionally, concerning gastroesophageal reflux disease, the cost of medical therapy based on endoscopic diagnosis alone was compared to that of medical therapy guided by these functional tests. Hence it was demonstrated that it is economically advantageous to study functionally all of the symptomatic patients, except the cases of esophagitis, and patients with atypical symptoms or with mild symptoms and endoscopic esophagitis of the first degree. It is not worthwhile investigating patients with second, third or fourth degree esophagitis, regardless of the symptoms, and patients with typical severe symptoms and first degree esophagitis. These functional tests are economically practical in all cases in which morphologic alterations are either absent or minimal.
Adolescent↗
[Esophageal manometry: methods of investigation and interpretation of results].
Standard manometry is still today the method of choice for investigating motor disorders of the esophagus. Fundamental elements in executing the test are suitable equipment, an execution technique following well established protocols and the adoption of univocal criteria for interpreting the results. In fact it is essential to use low compliance pneumo-hydraulic pumps and to perform the test in distinct steps to separately evaluate the features of the sphincter and the peristaltic activity of the esophageal body. Newly introduced technology (computerized analysis) authorizes an objective analysis of the tracing and the measurement of novel parameters, making it necessary however to re-evaluate the parameters of normalcy in the asymptomatic population. The manometric features of the lower esophageal sphincter, which define its competence (mean pressure at the point of respiratory inversion, abdominal length, total length), are probably better expressed by the mean pressure of the entire LES, by the area under the curve and by the Vector Volume. As far as motility of the esophageal body is concerned, computerized manometry provides for a more precise definition of the maximum amplitude of the esophageal contractions and an objective measure of their duration.
Esophagus↗
Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. The Italian Prostatic Cancer Project.
A total of 26 previously untreated patients with metastatic carcinoma of the prostate received the pure nonsteroidal antiandrogen nilutamide as a single agent. Objective response rate was 38.5 +/- 18.7% (95% confidence interval). Median progression-free survival and median survival were 9 and 23 months, respectively. Of 13 patients with progression on antiandrogen 5 showed an additional objective response to a second-line endocrine treatment. The drug was generally well tolerated, except for 2 patients who discontinued treatment because of moderate gastrointestinal symptoms. Approximately a third of the patients complained of decreased adaptation to darkness. An electroretinogram and dark adaptation test revealed the presence of functional damage and visual complaints reversed in all patients on cessation of therapy. The other most frequent side effects were slight nausea (26.9% of the patients) and alcohol intolerance (19.2%). A nonsignificant increase in testosterone levels was shown within 1 month of treatment, after which the levels remained stable. Approximately half of the sexually active men claimed maintenance of libido and sexual potency during treatment. A slightly significant increase in hemoglobin was observed during the long term, suggesting the occurrence of a trophic effect by androgens on erythropoiesis. The results indicate that nilutamide as a single agent has an acceptable toxicity and a moderate activity, and may maintain sexual interest in a discrete number of cases. Whether monotherapy with nonsteroidal antiandrogens offers a valid option in the palliation of advanced disease remains to be seen in comparative prospective trials.
Androgen Antagonists↗
Lung cancer risk among refractory brick workers exposed to crystalline silica: a retrospective cohort study.
We conducted a retrospective cohort study among 1,022 refractory brick workers exposed to crystalline silica. Mortality from lung cancer (SMR = 1.77) and respiratory diseases (SMR = 3.15) was elevated in workers first employed less than or equal to 1957 who are likely to have shared the highest exposure to crystalline silica. Workers with at least 19 years of cumulative employment in the plant experienced particularly increased risks for lung cancer (SMR = 2.01) and respiratory diseases (SMR = 3.89). Relative mortality from these specific causes increased with years since first employment (that is, first exposure) and decreased with age at first employment. Indirect adjustment for smoking habits and the lack of excess mortality from cardiovascular diseases and emphysema indicated little effect of smoking on the increased risks for lung cancer and respiratory diseases.
Adult↗
Limited clonal heterogeneity of antigen-specific T cells localizing in the pleural space during mycobacterial infection.
To detect possible differences in phenotype and fine specificity for mycobacterial antigens between CD4-positive T cells from peripheral blood (PB) and from inflammatory sites, we identified four patients presenting with a mycobacterial pleural exudate (PE) rich in PPD-specific lymphocytes and with a negative skin test to tuberculin purified protein derivative (PPD) and a negative proliferative response of PB lymphocytes to PPD at the same time. Several weeks after chemotherapy, these patients converted to PPD responsiveness in the periphery, and PPD-specific clones could be generated from PB at this stage. The phenotypic comparison of PE lymphocytes and concomitant PB lymphocytes obtained before treatment showed an increase of CD8 cells and a high frequency of HLA-DR-positive activated T cells in PE. The frequency of tetanus toxoid-specific and Candida albicans-specific proliferating T cells was lower than that of PPD-specific cells in PE but not in PB. PPD-specific clones were derived initially from PE and from PB once the patients had converted to PPD responsiveness. The two sets of clones from each patient were compared for proliferative response to mycobacterial antigen clusters of defined molecular weight ranges. A large number of PE-derived clones (36%) responded to a fraction of 27 to 35 kDa, whereas only one clone from PB responded to the same fraction. The purified antigen P32 (32 kDa), a soluble mycobacterial protein, stimulated PE-derived clones that were responsive to the 37- to 27-kDa fraction but did not stimulate PB-derived clones. The data demonstrate that PE- and PB-derived lymphocytes differ both in phenotype and in fine specificity, suggesting a limited clonal heterogeneity of T cells localizing at the inflammatory site in tuberculous patients without a PPD response in the periphery. Therefore T cells compartmentalized at inflammatory sites provide information that is different from that provided by T cells in the periphery.
Antigens, Bacterial↗
Hiccups and related esophageal motor disorders.
The clinical course of a patient with pyrosis and intractable hiccups is presented. Hiccups persisted six years after an effective fundoplication had cured pyrosis, and the patient was eventually treated with baclofen. Esophageal function during and after hiccups was studied in detail by means of esophageal manometry and 24-hour-pH monitoring. The relationship between hiccups and gastro-esophageal reflux is discussed.
Amantadine↗