Evaluation Of Therapeutic Response Research Articles

A double-blind comparative study of loratadine and astemizole in chronic idiopathic urticaria

Loratadine is a long-acting, orally effective, second-generation histamine H1-receptor antagonist with proven efficacy in the treatment of chronic idiopathic urticaria. It has an excellent safety profile, and is free of undesirable side-effects such as sedation and dry mouth which often accompany the use of the classic antihistamines. In the present 28-day study, loratadine was compared with astemizole, another second-generation H1 antihistamine, for the treatment of chronic idiopathic urticaria in 110 patients (99 valid). Patients with moderate to severe pruritus and dermal lesions due to urticaria were randomly assigned to receive either loratadine (10 mg once daily) or astemizole (10 mg once daily). Both loratadine and astemizole were found to be effective in relieving the symptoms of urticaria for the duration of the study. Symptom scores were reduced by roughly 50% in both treatment groups. The efficacy of the two antihistamines was statistically comparable as determined by scoring of urticaria symptoms, therapeutic response, and global evaluation of anti-itching effect. Furthermore, the incidence of adverse events related to treatment was low and was statistically comparable between the two treatment groups. However, inasmuch as three astemizole patients experienced severe sedation, the safety profile favored loratadine.

A clinical classification of severity of benign prostatic hyperplasia

The grading of severity of benign prostatic hyperplasia (BPH) was attempted by scoring clinical manifestations associated with the disease. The total score (0 to 100 points) is the sum total of subjective and objective one, each of which is 50 points at its maximum. Subjective score is composed of symptom score (0 to 25 points) evaluating 5 each obstructive and irritative symptoms and quality of life (QOL) score (0 to 25 points). Objective score consists of functional and anatomical scores. Functional score (0 to 25 points) is calculated by scoring maximum flow rate and residual urine. Anatomical score (0 to 25 points) is calculated by the score of prostatic volume. Seventy-seven BPH patients have been evaluated by this scoring system. The mean values of 4 kinds of scores (symptom, QOL, functional and anatomical scores) were about 8-9 points and thus comparable each other. The total score was 35.4 +/- 12.3 in the average and divided into 6 grades: Grade 0; < 10, Grade 1; > or = 10, Grade 2; > or = 20, Grade 3; > or = 30, Grade 4; > or = 40, Grade 5; > or = 50. The present scoring and grading systems appear to be appropriately formulated to estimate the global severity of BPH patients. Further studies to apply the system to evaluation of therapeutic responses would be mandatory to examine its validity.

Evaluation of therapeutic response using iodine-131-B72.3 monoclonal antibody in patients with ovarian carcinoma

We used radiolabelled monoclonal antibodies (MoAbs) to prove disease persistence after treatment for ovarian carcinoma. Twelve patients with histologically confirmed ovarian carcinoma were studied. They received 5 mCi (1 mg) of iodine-131-B72.3 by intravenous injection before and after a complete course of chemotherapy. Images were obtained with a LFOV gamma camera 2 h after MoAb administration and daily up to 6 days. Before treatment 8 patients had a true positive scan. Questionable antibody uptake was observed in 2 patients while 1 had a true negative scan and 1 a false-negative examination. After treatment the therapeutic response was evaluated. Five patients had partial remission and antibody scan showed persistence of disease in all patients except 1. Four patients showed progression of the disease and 1 no change. The antibody scan was positive in 4 and questionable in 1. Two patients had complete remission and negative antibody scans. Computed tomography (CT) could not always discriminate postoperative fibrosis from tumour lesions, especially when the peritoneum was involved in the disease. High serum levels of tumour markers were constantly associated with the presence of tumour lesions, but normal values did not guarantee absence of disease. We conclude than the antibody scan is complementary to CT and serum tumor markers in the definition of therapeutic response.

Human Lymphoblastoid Interferon (IFN-α-N1) Plus Doxorubicin, Cyclophosphamide, and Cisplatin in the Treatment of Advanced Epithelial Ovarian Malignancies A Phase I-II Study of the Gynecologic Oncology Group

This is a phase I-II study of lymphoblastoid interferon (IFN-alpha-N1) combined with primary chemotherapy after cytoreductive surgery in patients with suboptimal stage III and stage IV epithelial ovarian carcinoma. Fourteen patients were treated initially with cyclophosphamide, doxorubicin, and cisplatin (CAP regimen) for two cycles, and IFN (alpha-N1) was added to this combination on day 2 of the third cycle. Patients then were divided into four groups, each group receiving differing doses of IFN ranging from 3 to 10 MU/m2 on each of days 2-5. A total of eight courses of chemotherapy was administered, six of which included interferon. Severe fatigue and malaise were the greatest dose-limiting toxicities associated with the interferon. However, severe bone marrow suppression also limited the administration of interferon. The results of this study suggest that the addition of interferon to the multiagent chemotherapy regimen of CAP is both unacceptable to patients and excessively toxic to the bone marrow. Because of the small patient sample and poor tolerance of the treatment, an accurate evaluation of therapeutic response could not be performed.

TNF/TIL Human Gene Therapy Clinical Protocol: Addendum to Protocol, May 24, 1990

A tumor nodule will be resected from a patient with advanced cancer and the lymphocytes (TIL) infiltrating into this cancer deposit will be cultured and expanded in vitro using techniques previously used in our adoptive immunotherapy protocols. When these TIL have reached log phase growth, they will be incubated with a retroviral vector LTSN (containing genes for tumor necrosis factor and for neomycin resistance). These cells will then be expanded in culture until approximately 4 × 1010 cells are achieved. These TIL will then be cryopreserved in 1010 cell aliquots and tested to insure that they are free of replication competent virus and to determine the levels of tumor necrosis factor that are secreted. These gene-transduced TIL will then be administered to the cancer patient in escalating doses beginning at 1010 TIL along with 180,000 IU/kg of IL-2 every 8 hr for up to 5 days. Three weeks later the dose will be escalated to 3 × 1010 TIL and at 3-weekly intervals, escalated to 1011 and then to 3 × 1011 TIL. Extensive monitoring of patients will be performed to test for any toxic side effects resulting from the TIL administration. Studies of the survival and distribution of the gene-modified TIL will be performed by sequential sampling of blood, lymph nodes, and tumor biopsy material. Tests for in vivo production of tumor necrosis factor will be conducted by measuring serum TNF levels and tests for the presence of the TNF gene and the NeoR gene will be performed by PCR-DNA analysis. Evaluation of the possible therapeutic response of cancer deposits to this therapy will be measured. The maximum dose of gene-transduced TIL that can be safely administered, will be determined in at least 5 patients. In subsequent patients, transduced TIL will be selected in G418 and a similar escalating dose protocol will begin starting at 10% of the established safe number of unselected cells. When safe levels of nonselected and selected gene-transduced TIL are determined, the dose of IL-2 will be raised to 720,000 IU/kg in a subsequent series of patients.

Ultrasound, CT and MRI of ruptured and disseminated hydatid cysts

Three cases of echinococcus granulosus with rupture of hydatid cysts and widespread abdominal, pelvic or pleural dissemination are described. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) allowed recognition of ruptured hydatid cysts. This assisted to come to an appropriate therapy and exclusion or confirmation of hydatid cysts elsewhere in the body. Ultrasound, CT and MRI are also important for follow-up, evaluation of therapeutic response and/or early diagnosis of recurrence.

Computed Tomography of Malignant Ovarian Disease

One hundred and five patients with proven malignant ovarian disease were examined with one or more abdomino-pelvic CT scans in order to evaluate clinically suspected recurrence, complete clinical remission, or the effect of therapy. The findings obtained at CT were compared with follow-up examinations including surgery in 85 patients within 3 months. CT was accurate in the evaluation of therapeutic response, but if negative not reliable enough to replace a laparotomy of patients with possible recurrence or in clinical remission.

Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: Results of a multicenter, baseline-controlled safety and efficacy study in 160 patients

Efficacy and safety of esmolol in the treatment of supraventricular tachyarrhythmias (SVT) was evaluated in this open-label, baseline-controlled, multicenter study. One hundred sixty patients with SVT received an intravenous infusion of esmolol in doses ranging from 25 to 300 μg/kg/min for up to 24 hours. All of the 160 patients were evaluated for safety, and 147 of them were eligible for evaluation of therapeutic response. Therapeutic response was defined as ≥ 15% reduction in the average baseline heart rate or conversion to normal sinus rhythm. Seventy-nine percent (116 of 147) of the patients exhibited a therapeutic response. The cumulative percentage response increased significantly with increasing esmolol doses up to 200 μg/kg/min. The mean (±SEM) dose of esmolol producing a therapeutic response was 97.2 ± 5.5 μg/kg/min. Among all patients (n = 160), 39% exhibited hypotension. In 58% of these patients, hypotension resolved with or without adjustment of the esmolol dose while the infusion continued; among almost all of the remaining patients, hypotension resolved within 30 minutes after esmolol was discontinued. Most patients at risk for adverse effects during beta blockade (i.e., those with diabetes mellitus, congestive heart failure, asthma, etc.) tolerated esmolol therapy, and there were no clinically important trends among the reported changes in laboratory variables. The results of the study indicate that esmolol is effective and well tolerated for the treatment of SVT.

A Comparison of Naproxen Sodium to Propranolol Hydrochloride and a Placebo Control for the Prophylaxis of Migraine Headache

SYNOPSISA 17 week, double‐blind, randomized, parallel, multicenter study compared naproxen sodium 550 mg bid, propranolol hydrochloride 40 mg tid, and placebo in 129 patients with classical or common migraine. Daily efficacy data were collected during the 12 week full treatment phase. Characteristics measured included headache days, headache severity, nausea, vomiting and visual disturbances. Patients and investigators, separately, rated the overall response and tolerance to the medication at the end of the trial.Patients' daily records revealed a trend toward superiority in the reduction of headache frequency, headache severity, nausea and visual disturbances for naproxen sodium and propranolol hydrochloride when compared to the placebo. In the overall evaluation of therapeutic response, both patients and investigators favored naproxen sodium in comparison with placebo. In a similar paired comparison the patients, but not the investigators, judged the overall response to propranolol better than placebo. In the overall evaluation of tolerance, both the patients and investigators favored propranolol hydrochloride. The majority of patients reported a high incidence and severity of gastrointestinal complaints associated with naproxen sodium treatment than propranolol hydrochloride treatment. The incidence and severity of nongastrointestinal complaints related to naproxen and propranolol hydrochloride treatment were comparable.Headache activity occurring before and after the onset of menses was analyzed for a subset of 30 patients. Those treated with naproxen sodium experienced lesser headache frequency and severity during the week prior to menses, compared with the week after onset of menses. The difference in severity in the naproxen sodium treated patients was statistically significant when compared to the placebo treated patients and approached significance when compared to the propranolol hydrochloride treated patients.In this study naproxen sodium was shown to be an effective prophylactic medication for migraine. A long‐term study, to confirm these findings, seems warranted.

Propranolol for portal hypertension. Evaluation of therapeutic response by direct measurement of portal vein pressure

Portal vein pressure was measured before and after a week of oral propranolol hydrochloride therapy in 27 patients with alcoholic liver disease. Mean net portal pressure fell (14.5 +/- 3.3 to 12.5 +/- 4.5 mm Hg), but there was wide variation in individual response to the drug. Simultaneous transhepatic portal vein pressure and wedged hepatic vein pressure were similar before and one hour after a single oral dose of 40 mg of propranolol hydrochloride in six additional patients. Arterial, portal, and hepatic vein oxygen content did not change significantly. Propranolol hydrochloride appears not to dissociate portal and wedged hepatic vein pressure or to impair liver oxygenation. Because of variability of response, the portal hypotensive effect of propranolol should be documented before beginning therapy with the drug.

Radiographic evaluation of therapeutic response in bony metastases of breast cancer.

Response to chemotherapy was evaluated in 50 previously untreated patients with bony metastases of breast cancer. Lytic metastases respond in a definite sequence: sclerotic rim, filling-in, uniformly blastic, uniform fading. Increase in size of lytic areas of destruction in previously responding areas signals worsening. Mixed metastases are considered as beginning with a sclerotic rim. Response is otherwise similar. Particular attention is paid to the lytic areas. Blastic metastases are considered as beginning at the uniformly blastic stage. Progression is marked by a volumetric increase in blastic change or destruction in blastic regions. Change occurs slowly. Review of multiple studies is often necessary to reach the correct conclusion and clinical history is necessary.

Multicenter study of flunisolide aerosol in adult patients with steroid-dependent asthma

Seventy-three adult, steroid-dependent asthmatic patients participated in a 16-wk, double-blind study testing the efficacy of flunisolide aerosol. Forty received flunisolide, and 33 received placebo. The mean daily prednisone requirement of patients receiving flunisolide fell 59.2% during the testing period, and that of the patients receiving placebo fell 19.7%. The median daily prednisone dose dropped 74.4% in the flunisolide group and 4.2% in the placebo group (p = 0.006). In the flunisolide group 75% tapered use of oral steroids 50% or more, and 27.5% stopped taking oral steroids completely. In the placebo group 36% tapered use of oral steroids 50% or more, and only 12% stopped taking them completely. Despite their reduction in systemic steroids, those patients receiving flunisolide achieved significantly greater reduction in the daily severity of wheezing (p = 0.014) and frequency of asthma attacks (p = 0.049) than did those receiving placebo. In the final evaluation of therapeutic response, 70% of patients receiving flunisolide were rated as having a very good or good response, and 30% were rated as having a fair or poor response. In contrast 33% of patients receiving placebo were rated as very good or good, and 67% were rated as fair or poor (p = 0.0009). No serious reactions were reported. Plasma cortisols showed an average increase of 42.9% in the flunisolide group but no change in the placebo group. Flunisolide aerosol is a well-tolerated and effective agent in the treatment of steroid-dependent asthma.

Cell-mediated immunity to gluten fraction III in adult coeliac disease.

A migration inhibition test was used to assess sensitisation of blood leucocytes, and thus cell-mediated immunity, to gluten fraction III in controls and patients with coeliac disease. Migration indices were significantly less (indicating sensitisation) in untreated and in treated patients than in controls, and significantly less in treated patients than in untreated patients. At a concentration of 1 mg/ml gluten fraction III, 13% of untreated patients and 54% of treated patients had migration indices in the sensitised range. At 2 mg/ml gluten fraction III, sensitisation was demonstrated in 8% of untreated patients and 48% of treated patients. After starting a gluten free diet, migration indices fell into the sensitised range in all patients followed. After at least nine months on a gluten free diet, migration indices were significantly higher in those patients with a normal interepithelial lymphocyte count than in those patients with a raised interepithelial lymphocyte count. Cell-mediated immunity to gluten fraction III can be detected in the peripheral blood of certain patients with coeliac disease. Detectable sensitivity is related to the time on a gluten free diet, and the interepithelial lymphocyte count.

Changes in serum trace element levels following local irradiation of a solid tumor

The changes in concentrations of a number of trace elements have been determined by neutron activation analysis in tumor, liver, and blood serum of host animals, following local irradiation of a solid tumor (3924A Morris hepatoma). These trace element changes are compared to the changes observed in a parallel study of the effects of the chemotherapeutic agent 5-fluorouracil on the same tumor. Since the changes in some of the trace elements parallel the changes in pathological and biochemical factors resulting from the insult of radiation on the tumor, these trace elements may be valuable markers in the clinical evaluation of therapeutic response and as monitors of the long term effects of cancer therapy.

Ultrasonic and radionuclide scanning in pancreatic disease

Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies.

Ocular Pharmacology

<i>Ocular Pharmacology</i>by William H. Havener, MD, is an excellent text. It should be a standard on the shelf of every ophthalmologist from the first-year resident to the most senior staff member. It achieves the very difficult goal of being both a basic reference text and a stimulating, readable book. Chapters 1 ("Evaluation of Therapeutic Response"), 2 ("Routes of Administration"), and 33 ("Cataract") should be required reading for all residents at the very earliest level of their educational program. These chapters will also serve as a fascinating and informative review for ophthalmologists in practice. The chapter on corticosteroids may be the best chapter in the book and certainly one of great clinical importance. It well illustrates the author's particular ability for interweaving statistical data throughout a clinically-oriented treatise in a manner that should prove interesting to all types of readers. Dr. Havener has added a section, "Currently Employed Ophthalmic Therapy,"

SCIENTIFIC METHODOLOGY IN CLINICAL MEDICINE. I. INTRODUCTION, PRINCIPLES, AND CONCEPTS.

Special Article1 September 1964Scientific Methodology in Clinical MedicineI. Introduction, Principles, and ConceptsALVAN R. FEINSTEIN, M.D.ALVAN R. FEINSTEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-3-564 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe following paper is the first of four parts of Dr. Feinstein's cogent analysis of scientific methodology in clinical medicine. The subsequent parts will appear in consecutive issues of theANNALS,October through December, and are subtitled as follows: "II. Classification of Human Disease by Clinical Behavior," "III. The Evaluation of Therapeutic Response," and "IV. Acquisition of Clinical Data." These special articles should go far to demonstrate that the scientific heritage of Francis Bacon is just as relevant to the bedside of the patient as it is to the research laboratory. The practice of clinical medicine is surely an art,...Reference1. FEINSTEIN AR: Boolean algebra and clinical taxonomy. I. Analytic synthesis of the general spectrum of a human disease. New Eng. J. Med. 269: 929-938, 1963. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Haven, ConnecticutFrom the Department of Medicine (Clinical Biostatistics Section), Veterans Administration Hospital, West Haven, Conn., and the Department of Medicine, Yale University School of Medicine, New Haven, Conn.The work described here was conceived and prepared during investigations supported by grants HE01595 from the National Heart Institute and CA07155 from the National Cancer Institute, U. S. Public Health Service, Bethesda, Md.Requests for reprints should be addressed to Alvan R. Feinstein, M.D., Associate Professor of Medicine, Yale University School of Medicine, 333 Cedar St., New Haven, Conn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEvidence‐based medicine's curious path: From clinical epidemiology to patient‐centered care through decision analysisThe Development of Cancer Screening GuidelinesNovel aspects in diagnostic approach to respiratory patients: is it the time for a new semiotics?Oral Examination and ChartingWhat We Talk about When We Talk about Risk: Refining Surgery's Hazards in Medical ThoughtLogic Structure of Clinical Judgment and Its Relation to Medical and Psychiatric SemiologyPhilosophy and Concepts of Modern Spine SurgeryViewpoint: Envisioning the Successful Integration of EBM and Humanism in the Clinical Encounter: Fantasy or Fallacy?Central dimensions of clinical practice evaluation: efficiency, appropriateness and effectiveness - IIRelative Prognostic Importance of Histologic Invasion of the Laryngeal Framework by Hypopharyngeal CancerScientific Methodology in Temporomandibular Disorders. Part II: EthologyThe Teaching of Statistics in the Biological, Medical and Health Sciences: Some Comments and a Selected BibliographyPressure sore prevention and treatment: an example of nurses' failure to implement research findingsHistory-Taking and Development of the Examination RecordRound Table DiscussionINTRODUCTION TO EPIDEMIOLOGYA Short History of Evidence-Based MedicineEffect of Secretin in Celiac and Superior Mesenteric AngiographyCompassion, Computers, and the Regulation of Clinical TechnologyALVAN R. FEINSTEIN, M.D., F.A.C.P.Clinical and Intellectual Causes of Defective Statistics for the Prognosis and Treatment of Lung CancerThe Changing Emphasis in Clinical Research I. Topics Under Investigation. An Analysis of the Submitted Abstracts and Selected Programs at the Annual "Atlantic City Meetings" During 1953 Through 1965ALVAN R. FEINSTEIN, M.D., F.A.C.P., NEAL KOSS, M.D., JOHN H. M. AUSTIN, M.D.On statistical testing of prevalence studies“Time Present and Time Past are Both Perhaps Present in Time Future”Scientific Methodology in Clinical Medicine IV. Acquisition of Clinical DataALVAN R. FEINSTEIN, M.D., F.A.C.P.Scientific Methodology in Clinical Medicine III. The Evaluation of Therapeutic ResponseALVAN R. FEINSTEIN, M.D.Scientific Methodology in Clinical Medicine II. Classification of Human Disease by Clinical BehaviorALVAN R. FEINSTEIN, M.D. 1 September 1964Volume 61, Issue 3Page: 564-579KeywordsBehaviorBiostatisticsData acquisitionHeartHospital medicineMedical servicesResearch laboratories Issue Published: 1 September 1964 PDF downloadLoading ...

Obliterative Lymphangitis of the Mesentery In Whipple's Disease

Whipple's disease is a rare entity; to date, with the present case included, only some 70 cases have been reported in the literature. 1-56 A few of these cases, formerly considered to be examples of other conditions such as atypical sprue, chyle cysts of the mesentery, and mesenteric chyladenectasis, were in­ corporated into later reviews as representative examples of Whipple's disease. 9 Still others, first reported as Whipple's disease, have been discarded in subse­ quent reviews as exemplifying other entities or as incompletely substan­ tiated. 2 . 16 The vast majority of cases now accepted generally as authentic examples of Whipple's disease have been isolated instances, only seven groups of authors having had an opportunity to study more than one case.1, 16, 21, 26, 29, 31,54 Usu­ ally the disease is first recognized upon microscopic examination of autopsy material, so that detailed examination of pertinent features at gross autopsy, employment of certain special stains and chemical analyses, and the evaluation of therapeutic response are precluded. Such omissions, coupled with the rarity of the condition, have led to a divergence of opinion not only as to anatomic criteria for the diagnosis of Whipple's disease, but also as to pathogenesis. Most authors now agree that the pathologic anatomy is characterized by two principal lesions: (1) the mesenteric lymph nodes are involved in a cystic and lipogranuloma to us process; and (2) the mucosa of the small bowel is thick­ ened and infiltrated with large foamy macrophages. In addition, there mayor may not be overt evidence of chylous obstruction, i.e., dilated lacteals, dilated intestinal and mesenteric lymphatics and chylous ascites. Theories of pathogenesis, as tabulated by RUSSO,16 include the chemical or metabolic theory, which suggests defective fat metabolism or absorption, and the mechanical or inflammatory theory, which proposes an obstructive process involving some portion of the efferent lymphatic system. One of the stronger advocates of the mechanical or obstructive theory has been Clemmesen. 9 He postulated that the basic pathologic anatomy of Whip­ ple's disease is a chronic proliferative endolymphangitis involving predomi­ nantly the large efferent channels at the root of the mesentery. In the case pre­ sented below, this lesion initially proposed by Clemmesen is described for the