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Biomedical subjects

K Freeman

Publications and source records attributed to K Freeman.

At least 73 records · Page 4Linked to original sources

Continuously infused calcium hydroxide: its influence on hard tissue repair.

To study the ability of calcium hydroxide to promote hard tissue repair, Alza Alzet Osmotic Pumps, implanted in Sprague-Dawley rats, were used to deliver either calcium hydroxide and glycerol, barium hydroxide and glycerol, tetracycline and glycerol, or glycerol only to a standardized round bur defect in a rat femur. The pumps infused one of the reagents into the defects continuously over a 4-wk experimental period. The effects of each reagent on the healing of the bony defects were compared by histological evaluation. The Alza Osmotic Pump proved to be an effective method to deliver an agent to an experimental site. Our preliminary findings from a limited sample size indicated that calcium hydroxide contributed to a more complete osseous repair than either barium hydroxide or tetracycline. Barium hydroxide with a sustained pH equivalent to calcium hydroxide showed no greater healing than the controls. Tetracycline results were also similar to controls.

Animals↗

Effects of short-term and long-term androgen treatment on the diaphragm in male and female rats.

The effects of short-term (2.5 wk) and long-term (10 wk) testosterone propionate (2.5 mg/day; 5 days/wk) treatment on diaphragm contractility, fatigue resistance, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by direct stimulation at 37 degrees C. The fatigue paradigm consisted of 30 trains/min at 5 Hz (50% duty cycle) for 10 min. Fatigue resistance indexes were calculated as postfatigue divided by baseline forces. In females but not males, testosterone treatment produced significant increases in body weight, costal diaphragm weight, and contractility and significant decreases in fatigue resistance indexes. The interaction between testosterone treatment and the duration of treatment was significant, with the increase in contractility (females) being significant after short-term but not long-term treatment. No significant difference in fiber type proportions or areas was observed, regardless of treatment duration or the preexperimental, basal circulating level of androgen.

Animals↗

Colonic acetate in the circulating acetate pool of the infant pig.

To identify potential sites of acetate utilization and synthesis, we studied the contribution of colonic acetate to the circulating acetate pool in six neonatal pigs by the simultaneous i.v. infusion of [3H]acetate and colonic infusion of [14C]acetate. In the fasting state, the mean (+/- SEM) acetate concentration was 17 +/- 1 mumol/L in peripheral venous blood, 28 +/- 4 mumol/L in the femoral artery, and 46 +/- 4 mumol/L in portal blood. This concentration gradient implies that acetate was utilized either by peripheral tissues alone or by both liver and peripheral tissues. At the end of the 2-h intracecal acetate infusion, mean acetate concentration increased in the femoral artery to 186 +/- 20 mumol/L and in the portal vein to 333 +/- 31 mumol/L. In the fasted state, mean acetate concentration in the portal vein was on average 63% higher than the acetate concentration of the femoral artery, whereas specific radioactivity of the [3H]acetate in the portal vein was only 5% of that in the femoral artery. It is possible, therefore, that a high proportion of the arterial input of acetate is utilized by the portal-drained viscera. Our study identified the gastrointestinal tract as an important site of acetate utilization in the fasted state. Further, it showed that colonic acetate was efficiently absorbed and utilized in the gastrointestinal tract of infant pigs.

Acetates↗

Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation.

Primary central nervous system (CNS) lymphoma occurs frequently in patients with the acquired immune deficiency syndrome (AIDS). Seventeen patients with AIDS and biopsy-proven CNS lymphoma were treated with whole-brain radiation. At presentation, most patients were severely debilitated from previous AIDS-related illnesses. Patients generally had focal neurologic symptoms such as seizures and paralysis. Headaches and mental status changes, often noticed after hospital admission, seldom brought our patients to seek medical attention. Computed tomography (CT) scan showed low-density, contrast-enhancing, mass lesions with variable amounts of peritumor edema. Size, location, and pattern of contrast enhancement of the lesions varied. No specific pattern was seen that could be used to distinguish between CNS lymphoma, toxoplasmosis, or other CNS diseases that occur in patients with AIDS. Biopsy results showed angiocentric, high-grade, large cell tumors with frequent necrosis. Immunohistochemical analysis showed B-cell phenotype with small amounts of T-cells, presumably reactive. All patients received irradiation to the whole brain with parallel opposed fields. A variety of doses and treatment regimens were used. Mean survival was only 72 days. Survival was longer in patients with higher pretreatment Karnofsky scores. The correlation between dose and survival was not significant. At completion of therapy, most patients showed improvement in Karnofsky score and had partial improvement in neurologic symptoms. CNS lymphomas in patients with AIDS are responsive to radiation. Posttreatment CT scans showed regression of tumors. Autopsy examinations showed regression of tumors, but also showed concurrent CNS infections, AIDS encephalopathy, and radiation-induced changes within the normal CNS tissue. Opportunistic infections rather than cerebral herniation or uncontrolled lymphoma was the most common cause of death.

Acquired Immunodeficiency Syndrome↗

Survival differences in patients with AIDS.

To define the clinical, demographic, and behavioral variables that may influence survival in patients with AIDS, we studied 526 patients with AIDS diagnosed through September 1987 who were cared for at a single medical center. A diversity of racial and ethnic backgrounds, ages, both men and women, and all risk behaviors except hemophilia were well represented. The initial AIDS defining diagnosis was the most powerful predictor of survival. The median survival was 12.8 months for patients presenting with Kaposi's sarcoma (p less than 0.001), 10.9 months for patients presenting with Pneumocystis carinii pneumonia (p less than 0.001), and 4.8 months for patients presenting with other infections or neoplasms (p less than 0.02). For the entire series, male sex and younger age were associated with more favorable survival (p less than 0.025). For those presenting with Pneumocystis carinii pneumonia, in addition to younger age (p less than 0.025), black race (p less than 0.025) and the combination of male sex and intravenous drug use (p less than 0.005) were associated with a more favorable survival. Within a setting of comparable clinical care, survival from the point of diagnosis of AIDS is associated most strongly with the initial AIDS diagnosis, but differences in age, gender, race, and risk behavior also exert an influence on survival.

Acquired Immunodeficiency Syndrome↗

Enhancement of photodynamic cell killing (with chloroaluminum phthalocyanine) by treatment of V79 cells with the ionophore nigericin.

The K+/H+ ionophore nigericin dramatically increases killing of V79 cells by photodynamic therapy (PDT), when cells pretreated with 1 microM chloroaluminum phthalocyanine are incubated with nigericin before exposure to red light. Nigericin affects primarily the shoulder of the PDT dose-response curve, reducing the surviving fraction from 0.90 to 0.02 after a fluence of 7 kJ/m2 and from 0.80 to 0.0003 after a fluence of 12 kJ/m2. Optimal enhancement of PDT occurs when cells are incubated with 2 microM nigericin, at pHe 6.7, for 30 to 60 min before irradiation. However, significant enhancement of PDT also occurs when nigericin is added immediately before irradiation. Treatments with chloroaluminum phthalocyanine and nigericin, nigericin alone, or nigericin and red light are not toxic to cells. Cells treated with the combined agents display a rounded morphology 2 h after light exposure and lyse within 12 h. However, rounding of cells is not accompanied by severe depletion of ATP or by permeabilization of the plasma membrane to trypan blue. These results, together with known metabolic effects of nigericin, suggest that nigericin potentiates PDT by perturbing ion transport across either mitochondrial or plasma membranes.

Adenosine Triphosphate↗

Issues in the design of drug trials for AIDS.

Although the fundamental principles that drive the design, conduct, and analysis of clinical trials are as applicable to AIDS as to other diseases, there is no question that we have been confronted with unusually difficult challenges in studying therapeutic approaches in this disease area. Treatments are being developed that show great promise, but when investigated further some may be seen to offer no clinical benefit and others may do active harm through toxicity. A group of biostatisticians, meeting in association with the AIDS Clinical Trials Group (ACTG), has discussed and written a report on a number of issues, primarily related to principles of study design, with the goal of stimulating thought on new study designs and the timely implementation of well-designed trials to identify effective treatment strategies for HIV-infected populations. These issues include (1) progression of clinical trials through phases, (2) choices of outcomes, (3) breadth and complexity of clinical trials (eligibility criteria and "low-tech" trials, (4) alternative designs to be used in randomized trials, and (5) the concept of randomized clinical trials as a desirable option, both for patients and for science. The current HIV epidemic makes the requirements of obtaining valid scientific comparisons more important, not less so, but the challenge is to expedite this process.

Acquired Immunodeficiency Syndrome↗

Cough-cardiopulmonary resuscitation in the cardiac catheterization laboratory: hemodynamics during an episode of prolonged hypotensive ventricular tachycardia.

Cough-CPR, a deep rhythmic forceful cough repeated 30-60 times per minute, can be an effective resuscitative technique during emergencies occurring in the cardiac catheterization laboratory. We provide documented evidence on the potential of cough-CPR to maintain adequate systemic arterial blood pressure and consciousness during malignant ventricular arrhythmias, including the longest cough-CPR episode (75-90 sec), with continuous hemodynamics recorded. Results in three patients disclose that 1) mean arterial pressure during cough-CPR was 47-66% of nonarrhythmic baseline at a cough rate of 38-46% of normal sinus rhythm heart rate; 2) mean arterial pressure during hypotensive ventricular tachycardia was 17-60 mm Hg higher with than without cough-CPR; 3) at comparable diastolic pressures (33 vs. 31 mm Hg), systolic arterial pressure during cough-CPR was 40 mm Hg higher than basic CPR; and 4) consciousness can be maintained with cough-CPR during prolonged malignant ventricular arrhythmias. Thus cough-CPR can be a valuable adjunct in maintaining patient stability while definitive therapy for the malignant ventricular arrhythmia is administered.

Aged↗

Response to pneumococcal vaccine among asymptomatic heterosexual partners of persons with AIDS and intravenous drug users infected with human immunodeficiency virus.

Antibody responses to pneumococcal vaccine were studied in asymptomatic heterosexual partners of persons with AIDS and intravenous drug users seropositive for human immunodeficiency virus (HIV). Serum antibodies to 12 pneumococcal capsular antigens were measured by radioimmunoassay. Eleven intravenous drug users seropositive for HIV, 13 seronegative intravenous drug users, and 10 each seropositive and seronegative sexual partners received 23-valent pneumococcal vaccine. Additional unvaccinated matched seropositives served as controls. Antibody responses were significantly lower among subjects seropositive for HIV (P less than .05). Fourteen (88%) of 16 seropositive subjects with baseline type-specific antibodies to one or more pneumococcal antigens less than 300 ng of antibody nitrogen/ml (ngAbN/ml) demonstrated a rise in one or more of these antibodies to greater than 400 ngAbN/ml. No clinical deterioration or decrease in T4 cells attributable to vaccination was found. Although antibody responses to pneumococcal vaccine among HIV-infected subjects were impaired, most with antibody levels less than 300 ngAbN/ml developed titers of one or more type-specific antibodies to levels greater than 400 ngAbN/ml without notable adverse effects.

Acquired Immunodeficiency Syndrome↗

Therapeutic focus. Minocycline in the treatment of acne.

Minocycline has an established place in the oral therapy of acne. Prolonged courses of therapy have an acceptable safety profile. Where therapy with oxytetracycline has failed, minocycline is still likely to prove effective. The twice-daily dosage and ease of absorption from the gastrointestinal tract offer significant advantages over other tetracyclines. The simpler minocycline regime and early onset of clinical improvement are likely to result in better patient compliance, and hence optimise therapeutic response. There is therefore justification for the use of minocycline as first-line oral therapy, but, whether as a first- or second-line therapy, minocycline is a valuable drug in the treatment of this very distressing disorder. The earlier effective therapy is used in a patient with acne, the less physical and psychological scarring will remain thereafter.

Acne Vulgaris↗

Low occupational risk of human immunodeficiency virus infection among dental professionals.

We studied 1309 dental professionals (1132 dentists, 131 hygienists, and 46 assistants) without behavioral risk factors for the acquired immunodeficiency syndrome (AIDS) to determine their occupational risk for infection with human immunodeficiency virus (HIV). Subjects completed questionnaires on behavior; type, duration, and location of their dental practice; infection-control practices; and estimated numbers of potential occupational exposures to HIV. Serum samples were tested for antibodies to HIV and to hepatitis B surface antigen (unvaccinated subjects). Fifty-one percent of the subjects practiced in locations where many cases of AIDS have been reported. Seventy-two percent treated patients who had AIDS or were at increased risk for it. Ninety-four percent reported accidental puncturing of the skin with instruments used in treating patients. Adherence to recommended infection-control practices was infrequent. Twenty-one percent of unvaccinated subjects had antibodies to hepatitis B surface antigen. Only one dentist without a history of behavioral risk factors for AIDS had serum antibodies to HIV. We conclude that despite infrequent compliance with recommended infection-control precautions, frequent occupational exposure to persons at increased risk for HIV infection, and frequent accidental puncturing of the skin with sharp instruments, dental professionals are at low occupational risk for HIV infection.

Accidents, Occupational↗

Concerns of medical and pediatric house officers about acquiring AIDS from their patients.

To assess the degree of house officers' concerns about acquiring AIDS (acquired immunodeficiency syndrome) from their patients, we surveyed 263 medical and pediatric interns and residents in four housestaff training programs affiliated with seven New York City hospitals with large AIDS patient populations; 258 questionnaires (98 per cent) were returned. Thirty-six per cent of medical and 17 per cent of pediatric house officers reported percutaneous exposures to needles contaminated with blood of AIDS patients. Forty-eight per cent of medical and 30 per cent of pediatric house officers reported a moderate to major concern about acquiring AIDS from their patients. Greater concern about personal risk was noted in those house officers who were earlier in their residency training, who reported having treated a greater number of AIDS patients, and who were in medicine rather than pediatrics programs. Twenty-five per cent of all respondents reported that they would not continue to care for AIDS patients if given a choice. The results demonstrate a substantial degree of concern about acquiring AIDS among house officers caring for AIDS patients and suggest the need for housestaff program administrators for formally address these concerns.

Acquired Immunodeficiency Syndrome↗

Outflow resistance measurement during infrainguinal arterial reconstructions: a reliable predictor of limb salvage.

Criteria for abandoning infrainguinal arterial reconstructions in favor of major amputations should include reliable predictors not only of graft patency, but more importantly, of limb salvage. To evaluate the efficacy of intraoperative outflow resistance measurements in predicting limb salvage after infrainguinal bypasses, we have reviewed 134 such operations (64 femoropopliteal and 70 femorodistal bypasses) performed for critical ischemia. Outflow resistance measurements were divided into quartiles for femoropopliteal bypasses (Group A 0.17 mm Hg/ml/min or less, Group B 0.18 to 0.24 mm Hg/ml/min, Group C 0.25 to 0.4 mm Hg/ml/min, and Group D greater than 0.4 mm Hg/ml/min) and femorodistal bypasses (Group A 0.4 mm Hg/ml/min or less, Group B 0.4 to 0.58 mm Hg/ml/min or less, Group C 0.6 to 1 mm Hg/ml/min, and Group D 1 mm Hg/ml/min or greater). One year limb salvage rates for patients who underwent femoropopliteal bypass were 95 percent, 92 percent, 87 percent, and 67 percent from the lowest to the highest quartile (difference not statistically significant), and for those who had femorodistal bypass, they were 51 percent, 75 percent, 48 percent, and 0, respectively (p less than 0.05). Interestingly, 12 month graft patency and limb salvage rates for patients who underwent femorodistal bypass with outflow resistances between 0.59 and 1 mm Hg/ml/min did not correlate well (22 percent and 48 percent, respectively), whereas for those with outflow resistance greater than 1 mm Hg/ml/min, they were 22 percent and 22 percent, respectively. Thus, measurement of intraoperative outflow resistance is a very accurate predictor of limb salvage after infrainguinal bypass operations.

Adult↗

Short-contact anthralin therapy for psoriasis using an aqueous cream formulation.

A pilot study of five patients was conducted using an aqueous anthralin cream (Drithocreme) and demonstrated that between twenty and forty minutes was an effective contact time to produce an improvement in induration of psoriatic plaques. In a further, bilateral controlled study, the anthralin cream was used to treat twenty patients with symmetrical chronic plaque psoriasis. The cream was applied to one side of the body overnight and then to the other side in the morning. Thirty minutes later it was washed off both sides in a bath or shower. The results indicated that both overnight and short-contact treatment were equally effective, and the short-contact treatment reduced staining and irritation.

Adult↗

Clinical evaluation of fenticonazole cream in cutaneous fungal infections: a comparison with miconazole cream.

A randomized, double-blind, parallel-group, multi-centre clinical trial was undertaken in 60 patients with dermatophytosis or pityriasis versicolor to compare topical 2% fenticonazole cream with topical 2% miconazole cream. Treatment, by twice-daily application, was for 4 weeks or until earlier complete resolution of disease. Assessment was by laboratory mycological investigation and regular clinical/symptomatic evaluation, both during and for 2 to 6 weeks after therapy. Fifty-three patients satisfactorily completed the trial, 28 of whom received fenticonazole and 25 miconazole. The groups were adequately well-matched. All assessment criteria showed fenticonazole to be at least as efficacious as miconazole, with no statistically significant differences between the two treatments. A number of assessment criteria, however, did show trends in favour of fenticonazole. Fenticonazole resulted in mycological findings becoming negative in 92%, i.e. all but 2 of 25 patients, by the end of treatment and a similar proportion (91%, 21 of 23 patients) remained mycologically negative 2 to 4 weeks after the end of therapy. With miconazole, only 79% (19 of 24 patients) became mycologically negative during treatment and this figure decreased further to 74% (14 of 19 patients) after therapy. Essentially similar results were seen for clinical assessments of erythema, itching and desquamation, these features being significantly and progressively eliminated or improved by both treatments in high proportions of patients during therapy, followed by little tendency to return after the cessation of therapy. Overall clinical assessments demonstrated statistically significant improvement during the second, third and fourth weeks of treatment with both drugs. Only 4 patients (two with each treatment) were reported as showing clinical deterioration at any stage during the trial, in all cases after the end of therapy. There were no reports of local or systemic adverse reactions to either drug, and laboratory screening investigations failed to reveal any signs of toxicity. These results indicate that a 4-week course of twice daily topical 2% fenticonazole cream is extremely well tolerated and is at least as efficacious as an equivalent regimen of 2% miconazole for the treatment of cutaneous dermatophytosis or pityriasis versicolor. Trends in the results suggest that fenticonazole may prove to be more efficacious than miconazole, particularly in relation to elimination of laboratory evidence of persistent fungal infection, which could be reflected in a lower incidence of subsequent relapse of the disease.

Adolescent↗