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Biomedical subjects

J Keller

Publications and source records attributed to J Keller.

At least 199 records · Page 11Linked to original sources

Myelostimulatory activity of recombinant human interleukin-2 in mice.

In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy.

Animals↗

[Patellar fractures. Modified tension band osteosynthesis].

In a retrospective investigation, the ability of modified tension band osteosynthesis to retain 45 reduced fractures of the patella and the functional end result was studied. Postoperatively, 24 patients were immobilized in plaster casts for 0-14 days and the remainder for 25-56 days. Postoperative radiographs revealed nine fractures (four transverse, three comminuted and two pole fractures) with fragment displacements exceeding 2-3 millimeters. Among these, three fractures had secondary dislocation and, further, one exactly reduced pole fracture dislocated. Operation was complicated with infection in four cases: two superficial wound infections, one subcutaneous fistula and one pyarthron. Operative release of adhesions was performed in five cases, two patients were patellectomized and one required a condyle prosthesis. At follow-up 18-80 months after the injury, 37 patients were examined clinically. Among 29 patients without concomitant injuries, seven patients were free of symptoms and 13 patients were without any pain. Free knee movement and quadriceps atrophy less than or equal to 1.5 cm was found in 17 patients. The modified tension band can retain adequately reduced transverse and comminuted fractures of the patella, probably also without plaster immobilisation. Dislocated fracture of the patella is a serious lesion, which must be treated with care.

Adolescent↗

The effect of chronological and theoretical birth order on sexual attitudes and behaviors.

A survey designed to evaluate the impact that both chronological and theoretical birth order may have on sexual attitudes and behaviors was completed by 441 respondents (221 male, 220 female). The attitudes and behaviors investigated were aggressive sexual behavior, social relationship attitudes, emotional relationship attitudes, total heterosexual behavior, and total orgasmic behavior. The data revealed no difference between male and female in terms of total sexual behavior. However, males had significantly higher sexual aggression, social attitudes, emotional attitudes, and total orgasm scores. These results suggest that while there may be equity between the sexes in terms of heterosexual behavior, there are still significant differences between the sexes in terms of specific behaviors and attitudes. No differences were found on any of the scales based on either chronological or theoretical birth order. These results suggest that sexual behavior and attitudes may be influenced to a greater degree by biological and cohort factors than by sibling position.

Adolescent↗

Measuring functional status in chronic lung disease: conclusions from a randomized control trial.

The optimal method of assessing the effect of treatment on the day-to-day function of patients with chronic airflow limitation is not established. Therefore, we examined the performance of the Six Minute Walk test, a rating of dyspnea following the test and three different questionnaires measuring dyspnea in daily activities, in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primarily fixed chronic airflow limitation. Clinically important and statistically significant effects of salbutamol and theophylline on dyspnea during day-to-day activities were detected by each measure, but the Chronic Respiratory Questionnaire (CRQ) appeared more powerful than either the Oxygen Cost Diagram or the Medical Research Council Dyspnea Questionnaire as modified by the Rand Corporation. Changes in the CRQ dyspnea score showed a higher correlation with changes in spirometry, walk test score, dyspnea following the walk test, and global ratings of dyspnea than did the other two measures. Results of the walk test demonstrated statistically significant salbutamol and theophylline effects, but suggested that no added benefit could be obtained with both drugs; the rating of dyspnea following the walk test, however, was consistent with an additive effect. We conclude that the CRQ is a responsive, valid measure of functional status for clinical trials in chronic lung disease, and that when the six minute walk is used as a measure of outcome, dyspnea following the walk test should be measured.

Albuterol↗

Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry.

A registry of suspected cases of cancer-associated hemolytic-uremic syndrome (C-HUS) was established in May 1984. Records of 85 patients from the registry, all with history of cancer, hematocrit less than or equal to 25%, platelet count less than 100,000, and serum creatinine greater than or equal to 1.6 mg/dL were subjected to in-depth analysis. Eighty-nine percent of patients had adenocarcinoma, including 26% with gastric cancer. Microangiopathic hemolysis was reported in 83 patients; coagulation studies were normal with rare exception. Bone marrow examination ruled out chemotherapy-induced myelosuppression in 68 of 85. Thirty-five percent of patients were without evident cancer at time of syndrome development. Mitomycin (MMC) was part of the treatment regimen in 84 patients; all but nine received a cumulative dose greater than 60 mg. Pulmonary edema, generally noncardiogenic, developed in 65% of patients, often after blood product transfusions. C-HUS has a high mortality: over 50% of patients died of or with syndrome, most within 8 weeks of syndrome development. Conventional treatment was ineffective, although ten of 21 treated with staphylococcal protein A (SPA) immunopheresis showed significant responses. Statistical analysis found only absence of obvious tumor and treatment with SPA to suggest favorable prognosis. C-HUS is distinguishable from related syndromes such as childhood HUS, thrombotic thrombocytopenic purpura (TTP), consumption coagulopathy, and microangiopathic hemolysis associated with advanced carcinoma. MMC is likely involved in the development of C-HUS; the risk of developing C-HUS after treatment with MMC is between 4% and 15%. However, possible bias in patients referred to the registry and reports of non-MMC C-HUS cases must be remembered. Recommendations include careful monitoring of renal and hematologic function in patients treated with MMC, aggressive nontransfusion in patients with suspected C-HUS, and consideration of treatment with SPA immunopheresis in patients with definite syndrome.

Adenocarcinoma↗

Indomethacin and bone remodeling. Effect on cortical bone after osteotomy in rabbits.

Remodeling in cortical bone close to a plated tibial midshaft osteotomy was histomorphometrically evaluated in 32 rabbits. The animals were divided into two groups, one being treated with indomethacin (10 mg/kg per day) and the other receiving placebo. In the placebo-treated group, the remodeling activity was higher in the osteotomized leg compared with the intact leg. Two and 6 weeks after osteotomy, the number of resorptive and formative foci was reduced in the indomethacin-treated group compared with the placebo group. Porosity did not differ between the groups after 2 weeks; but after 6 weeks, it was reduced in the indomethacin-treated animals. Throughout the study, the bone formation rate did not differ between the two groups. This study demonstrates that indomethacin inhibits the remodeling of traumatized bone.

Animals↗

The use of anesthesia for surgical treatment of Achilles tendon rupture.

The influence of the type of anesthesia on the treatment and final results of Achilles tendon surgery was investigated. Open repair of Achilles tendon rupture was performed using general or spinal anesthesia in 80 patients and local anesthesia in 42 patients. Surgery using local anesthesia was very acceptable to the patients and was less resource-demanding than surgery using general anesthesia. The functional result was good in both groups and only minor differences in the functional results between the two groups were found.

Achilles Tendon↗

Effect of prostaglandin E2 and indomethacin on blood flow in the lower urinary tract of the rabbit.

The effect of the cyclooxygenase system on lower urinary tract blood flow was investigated in a standardized rabbit model with empty bladder. Twenty-eight New-Zealand white rabbits were separated into 3 groups. The first group received 1 mg per kg b.w. s.c. daily of PGE2 for 4 days. The second group received 10 mg per kg of indomethacin perorally daily for 7 days. The third group served as controls. The experiments were undertaken in general anaesthesia. Regional blood flow of the lower urinary tract was measured with 141Ce-labeled microspheres and plasma volume was assessed by the equilibrium distribution of 125I-labeled fibrinogen in tissues. Peroral treatment with indomethacin caused a significant increase in blood flow in the trigone. No difference in whole bladder blood flow was found and no differences were found among groups with respect to plasma volume.

Animals↗

A clinician's guide for conducting randomized trials in individual patients.

In determining optimal treatment for a patient conventional trials of therapy are susceptible to bias. Large-scale randomized trials can provide only a partial guide and have not been or cannot be carried out for most clinical disorders. However, randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may in some circumstances provide a solution to this dilemma. In an N of 1 RCT a patient undergoes pairs of treatment periods (one period of each pair with the active drug and one with matched placebo, assigned at random); both the patient and the clinician are blind to allocation, and treatment targets are monitored. N of 1 RCTs are useful for chronic, stable conditions for which the proposed treatment, which has a rapid onset of action and ceases to act soon after it is discontinued, has shown promise in an open trial of therapy. The monitoring of treatment targets usually includes quantitative measurement of the patient's symptoms with the use of simple patient diaries or questionnaires. Pairs of treatment periods are continued until effectiveness is proved or refuted. The cooperation of a pharmacy is required for the preparation of matching placebos and conduct of the trial. Formal statistical analysis may be helpful for interpreting the results. The practical approach presented in this paper allows clinicians to conduct their own N of 1 RCTs.

Clinical Trials as Topic↗

Electrocardiographic estimate of left ventricular mass versus radiographic cardiac size and the risk of cardiovascular disease mortality in the epidemiologic follow-up study of the First National Health and Nutrition Examination Survey.

The prognostic value of a left ventricular (LV) mass index (g/m2) estimated from an electrocardiographic model and radiographic estimates of the relative heart volume (ml/m2) and cardiothoracic ratio for predicting the risk of cardiovascular disease mortality were investigated using Cox regression analysis to adjust for age, systolic blood pressure and history of heart attack in 1,807 men (1,609 white, 198 black) and 2,143 women (1,884 white, 259 black). The study population (ages 35 to 74 years at baseline) was followed from 5 to 12 years (average 9.5 years) for cardiovascular disease mortality. LV mass index and relative heart volume were independent predictors of cardiovascular disease mortality among white men. All 3 cardiac size estimates were independent predictors for cardiovascular disease mortality among white and black women. When LV mass index was used as a dichotomized variable to indicate the presence or absence of LV hypertrophy, the age-adjusted relative risk of cardiovascular disease mortality was 2.48 (95% confidence interval 1.77 to 3.46) for white men, 3.03 (1.49 to 6.16) for black men, 1.86 (1.21 to 2.87) for white women and 2.05 (0.83 to 5.05) for black women. The corresponding prevalence of LV hypertrophy was 15.4% for white men, 36.6% for black men, 20.1% for white women and 17.4% for black women. It is concluded that the electrocardiographic estimate of LV mass index can identify a substantially larger fraction of persons at increased risk for cardiovascular mortality than conventional electrocardiographic criteria for LV hypertrophy and that LV mass index estimated by electrocardiogram is a valuable supplement to radiographic cardiac size estimates in epidemiologic applications.

Adult↗