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Biomedical subjects

M Farmer

Publications and source records attributed to M Farmer.

At least 37 records · Page 2Linked to original sources

Combined acute respiratory and renal failure: management by continuous hemodiafiltration.

OBJECTIVES: To study the impact of continuous hemodiafiltration (CHD) on the morbidity and mortality of acute combined respiratory and renal failure in critically ill patients. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit of a tertiary institution. PATIENTS: One-hundred fifteen critically ill patients with combined acute respiratory and renal failure. INTERVENTIONS: Treatment of all patients with either continuous arteriovenous hemodiafiltration (CAVHD) or continuous venovenous hemodiafiltration (CVVHD). MEASUREMENTS: Assessment of illness severity, measurement of plasma urea, serum creatinine, electrolytes and arterial blood gases prior to and during treatment. Duration of oliguria, ICU stay, hospital stay, and final outcome. RESULTS: One hundred fifteen critically ill patients with combined respiratory and renal failure (mean APACHE II score, 28.1; mean number of failing organs, 4.1) were studied. Thirty-five were treated with CAVHD and 80 with CVVHD for a mean treatment duration of 13.1 days per patient (range 2-47). Blood urea concentration fell from a mean of 29.4 mmol/l to a mean of 19.1 mmol/l (P < 0.001) and the serum creatinine concentration fell from a mean of 520 mumol/l to a mean of 374 mumol/l after 24 h of therapy (P < 0.001). The A-a gradient fell from a mean of 301 mmHg to a mean of 242 mmHg (P < 0.05). Despite the high degree of illness severity and the need for vasoactive drug infusion in 105 patients (91.3%), survival to hospital discharge was achieved in 33 patients (28.7%). For patients who required > 72 h of combined mechanical ventilation, survival was 22% (22 of 100 patients). Complications of continuous hemodiafiltration were few and all related to arterial vascular access. CONCLUSIONS: In critically ill patients with combined acute respiratory and renal failure, continuous hemodiafiltration controlled azotemia without hypotension and with early improvement in gas exchange. PATIENTS treated with this approach achieved promising survival rates. Our findings support the view that CHD is safe and effective and that it offers important advantages over intermittent hemodialysis. It may be the dialytic therapy of choice in critically ill patients with combined acute respiratory and renal failure.

Acute Kidney Injury↗

A prospective study of continuous hemodiafiltration in the management of severe acute renal failure in critically ill surgical patients.

Severe acute renal failure associated with surgical disease and a highly catabolic state poses a major therapeutic challenge. Treatment by conventional dialysis or arteriovenous hemofiltration suffers from serious shortcomings. The current study assesses the clinical and biochemical impact of a newer approach (continuous hemodiafiltration) in a cohort of 60 critically ill surgical patients with severe renal failure. All patients were studied prospectively and assessed for illness severity. Their biochemical response to therapy was analyzed and their clinical course to either death or hospital discharge documented. The use of continuous hemodiafiltration (CHD) permitted full control of azotemia in all patients (mean steady-state urea concentration: 19.8 mmol/L) and was associated with rapid control of acidemia (mean pretreatment pH: 7.27; mean ph after 24-h treatment: 7.35; p < .001). During the 15,696 h of therapy, there were no treatment-induced episodes of hypotension and/or hypoxemia. All patients were able to receive full-dose enteral (9) or parenteral (51) nutritional support with 1.5 to 2.5 g/kg/day of protein as tolerated. Despite their illness severity (mean APACHE II score: 28.9) and the need for vasopressor support and ventilation in 90% of cases, 21 patients (35%) survived to hospital discharge. We conclude that continuous hemodiafiltration is safe and effective in surgical critically ill patients with acute renal failure, and that it is associated with a low morbidity and an encouraging survival rate.

APACHE↗

The outcome of critically ill elderly patients with severe acute renal failure treated by continuous hemodiafiltration.

OBJECTIVES: To study the outcome of critically ill elderly patients with severe acute renal failure managed by continuous hemodiafiltration. DESIGN: Prospective study. SETTING: Intensive Care Unit of tertiary institution PATIENTS: Seventy-two consecutive critically ill patients of 65 years or older admitted to the ICU with severe acute renal failure. Seventy similar control patients of age < 65 years. INTERVENTION: Treatment of all patients with continuous hemodiafiltration. MEASUREMENTS AND MAIN RESULTS: Safety and effectiveness of therapy were assessed. Main outcome measures were duration of oliguria, of ICU stay, and hospital stay for survivors, and survival to ICU discharge and to hospital discharge. Mean APACHE II score on admission was 29.8 (95% confidence interval: 28.5 to 31.1) and mean organ failure score prior to initiation of continuous hemodiafiltration was 3.9 (95% confidence interval: 3.6 to 4.2). Sepsis was present in 51 cases (70.8%) and bacteremia or fungemia in 24 (33.3%). Fifty-three (73.6%) required mechanical ventilation for > 3 days. Vasopressor drugs were used in 65 (90.2%). Continuous hemodiafiltration controlled azotemia in all patients and was only associated with minor complications. Thirty-four patients (47.2%) survived to ICU discharge and 30 (41.6%) to hospital discharge. Among survivors, duration of oliguria was 11.6 days (95% confidence interval: 9.1 to 14.1), mean duration of ICU stay 8.6 days (95% confidence interval: 6.1 to 11.) and mean duration of hospital stay 33.1 days (95% confidence interval: 28.8 to 37.4). No statistically significant difference in survival was found when these patients were compared to a control group of similar but younger patients who also received ICU care and continuous hemodiafiltration for the treatment of severe acute renal failure. CONCLUSIONS: A greater than 40% survival was achieved in critically ill elderly patients with severe acute renal failure by the use of continuous hemodiafiltration. These patients had an in hospital survival comparable to that of younger patients. These findings support an aggressive renal replacement approach in such patients and suggest that continuous hemodiafiltration may be ideally suited to their management.

Acute Kidney Injury↗

Bringing parents into school clinics: parent attitudes toward school clinics and contraception.

Prior to implementing a change in school clinic policy to allow dispensing of contraceptives, parents of school-based clinic (SBC) enrollees were surveyed regarding attitudes toward clinic quality of care, desired services, and contraceptive distribution. Telephone interviews were conducted with a systematic sample of 262 parents who normally are in charge of the adolescent's health care. Parental opinion was felt to be crucial in shaping Baltimore SBC contraception policy. Parents overwhelmingly endorsed current clinic services including family planning for sexually active teens, annual physicals, and drug and alcohol counseling. Most parents rated the SBC as excellent (25%) or very good (36%), although a substantial minority found it difficult to rate the clinics (27%, "don't know"). Parents with prior verbal contact (45%) were more likely to rate the clinic as excellent (35% versus 16%) and less likely to respond "don't know" (13% versus 38%, p less than 0.001). Parent attitudes toward contraception was context specific: 63% endorsed and 27-30% opposed prescribing and dispensing. If a boy (or girl) was already having sex, 76% (or 75%) of parents supported and 14% (or 17%) opposed providing birth control pills or condoms. With parental permission, 93% supported contraception and only 3% were opposed. No differences were found by age, race, gender, or grade of student. Prior verbal communication with the clinic did not affect parent attitudes toward contraception. Consideration of parent attitudes was critical to changing SBC contraceptive dispensing policy in Baltimore. Contraceptive distribution, after counseling and necessary medical care, was initiated in September 1990. The parent and community response has been very supportive.

Adolescent↗

Validation of virus inactivation by heat treatment in the manufacture of diaspirin crosslinked hemoglobin.

Diaspirin crosslinked hemoglobin (DCLHb), a hemoglobin based oxygen carrying solution prepared from outdated human blood, is subjected to a heat treatment step to inactivate viruses in our manufacturing process. To validate the efficacy of this inactivation, we have simulated the heat treatment procedure at a reduced scale using hemoglobin solution spiked with representative viruses. Human Immuno-deficiency Virus (HIV), Cytomegalovirus (CMV), and Duck Hepatitis B Virus (DHBV) were used in this validation. Inoculation with concentrated virus was performed just prior to the heat treatment to determine the effect of that specific process step. Samples were taken before, during, and after heat treatment and assayed for virus titer in an attempt to assess the rate as well as the extent of virus inactivation. CMV was analyzed in a plaque assay using MRC-5 indicator cells. The titer was reduced from 3.3 x 10(6) plaque forming units (PFU) per mL to less than 5 x 10(1) PFU/mL (detection limit) within 30 minutes. DHBV was analyzed by inoculation of serially diluted samples into Pekin ducklings, followed at intervals by screening sera for DHBV DNA by dot blot hybridization. The titer was reduced from 5.0 x 10(6) duck infectious units (DIU) per mL to less than 5 x 10(0) DIU/mL (detection limit) within 1 hour. HIV titers were determined through an ELISA assay for p24 antigen present in peripheral blood lymphocyte cocultivation supernatants. The titer was reduced from 2.0 x 10(4) infectious units (IU) per mL to less than 2 x 10(0) IU/mL (detection limit) within 1 hour. These data indicate that high titers of these blood borne viruses are rapidly inactivated by this heat treatment process.

Aspirin↗

Trace element analyses of diaspirin cross-linked hemoglobin solutions.

A sensitive assay using inductively coupled plasma atomic emission spectroscopy (ICP-AES) has been applied to the measurement of trace elements in diaspirin cross-linked hemoglobin (DCLHb) solutions. Calcium, magnesium, zinc and iron were the only elements detected at greater than background levels. Ag, Al, As, B, Ba, Bi, Cd, Co, Cr, Cu, Mn, Mo, Pb, Sb, Se, Si, Sr, Ti, and V were present at concentrations either equal to the acid blanks or were not detected. Detection of non-heme iron (not incorporated into the hemoglobin porphyrin ring) in a 10 g/dL hemoglobin solution required the development of a special protocol. In this protocol a chelator, DTPA, was added to hemoglobin solutions to complex with both free and non-specifically bound non-heme iron. The resulting iron:DTPA complexes were separated from the hemoglobin molecules by ultrafiltration and the ultra-filtrate analyzed by ICP-AES. A modification of this assay in which the DTPA was omitted was used to measure the free non-heme iron in solution. Typical concentrations of chelatable (free and non-specifically bound) and solution (free) non-heme iron in DCLHb production lots at the completion of manufacture were 0.5-1.0 ppm and 0.1-0.3 ppm, respectively.

Aspirin↗

Long-term follow-up of treatment of thyrotoxicosis by three different methods.

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%. At 5 years, 18% were hypothyroid, the prevalence rising to 42% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7%. The rate of hypothyroidism at 5 years (38.5%) was higher than that found in the calculated dose group. A minimum 10-year follow-up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2%. The prevalence of hypothyroidism (2% at 5 years, 27.5% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thyroxine-binding prealbumin gene polymorphism: a population study.

The human thyroxine-binding prealbumin (TBPA) gene was examined for restriction fragment length polymorphism (RFLP) in normal subjects and a subject with euthyroid hyperthyroxinaemia, due to increased thyroxine binding by TBPA, using 16 restriction enzymes. Only Taq I and Msp I were shown to detect RFLPs. In a male of the normal population and one of his daughters, an additional Taq I site was found in the 3'-flanking region of the TBPA gene. The RFLP in a subject with euthyroid hyperthyroxinaemia was due to the deletion of a MspI site. All three subjects with RFLPs were heterozygous.

Adult↗

Immunologic studies of alveolar macrophages from patients with metastatic renal cell carcinoma.

Alveolar macrophage function in patients with renal carcinoma, a disease characterized by frequent pulmonary metastases, has not been examined. The purpose of this study was to evaluate tumoricidal responses of alveolar macrophages in renal carcinoma to determine if such activity is compromised. Alveolar macrophages and/or blood monocytes were obtained from 26 normal volunteers and 16 patients with renal carcinoma. Tumoricidal activity of alveolar macrophages and monocytes was assessed against 3H-thymidine-labeled tumor target cells. Patient alveolar macrophages and monocytes exposed to lipopolysaccharide (LPS) or recombinant interferon-gamma expressed tumoricidal activity comparable to those in normal subjects. Activated alveolar macrophages recognized and lysed neoplastic cells (including allogenic renal carcinoma cells), but not nonneoplastic cells. Alveolar macrophage and monocyte tumoricidal responses of patients with pulmonary metastases were not different from those of patients with metastases to other sites. These results indicate that alveolar macrophages from patients with renal carcinoma with or without pulmonary metastases are not compromised in vitro, but respond to immunomodulators with enhanced tumoricidal activity in the same fashion as do alveolar macrophages from normal volunteers.

Adult↗

Letter identification declines with increasing retinal eccentricity at the same rate for normal and dyslexic readers.

It has recently been claimed (Geiger & Lettvin, 1987; Perry, Dember, Warm, & Sacks, 1989) that the acuity/eccentricity function is flatter in dyslexics than in normal subjects, with dyslexics showing better performance in the periphery and worse performance at fixation. In these studies, all target letters were presented to the right of fixation, a procedural flaw inviting subjects to optimize performance by directing attention and/or gaze to the right of the designated fixation point. It is suggested that dyslexic and normal readers may differ in the degree to which they might adopt the optimal strategy in this situation. To overcome this problem, target letters were briefly presented at 16 randomly intermixed locations derived from the orthogonal combination of four eccentricities and four directions from fixation (above, below, right, left). The accuracy of letter identification declined with increasing eccentricity at the same rate for good and poor adult readers and dyslexic teenagers. This finding provides no support for the view that the acuity/eccentricity function might vary with and possibly cause differences in reading level.

Adult↗

Acetabular cup-siting device for total hip arthroplasty.

A method for improving acetabular cup positioning at arthroplasty is introduced. The anatomic and engineering principles involved are explained. The device used for this method of siting is described. The method was tested in cadaver experiments and resulted in a 380% improvement of anteversion-retroversion position and a 370% improvement in abduction position over conventional siting. The value of this method in conventional and revision arthroplasty is suggested.

Cadaver↗

Induction of in vitro tumoricidal activity in alveolar macrophages and monocytes from patients with lung cancer.

Human alveolar macrophages (AMs) and blood monocytes were obtained from 65 smoking and nonsmoking normal volunteers and 29 patients with lung cancer. The oxidative metabolic response of these cells was measured by superoxide anion production after incubation with lipopolysaccharide. In addition, tumoricidal activity of AMs and monocytes was assessed against [3H]thymidine-labeled tumor target cells. Smoking was associated with depressed AM superoxide anion responses in normals but not in patients. In contrast, smoking appeared to slightly elevate monocyte superoxide anion activity. AMs and monocytes exposed to lipopolysaccharide or recombinant gamma-interferon showed tumoricidal activity in all groups. Mean cytotoxicity values of smoking patients versus smoking normals and exsmoking patients versus nonsmoking normals were not significantly different. Smoking, however, in both patients and normals was associated with significantly (P less than 0.005) depressed AM cytotoxicity levels (less than 40%) compared to nonsmoking volunteers and exsmoking patients. Activated AMs from cancer patients and normals were cytotoxic against three different tumorigenic cell lines but not against a nontumorigenic line. No correlation between monocyte and AM cytotoxic activity within single individuals was found. We conclude that AM and monocytes from smoking and exsmoking patients can be activated after exposure to immunomodulators; however, smoking may be slightly suppressive to cytotoxic responses. These studies provide a rationale for clinical trials of immunomodulators in patients with lung cancer.

Adult↗

Human alveolar macrophage function: differences between smokers and nonsmokers.

Human alveolar macrophages and peripheral blood monocytes were obtained from smoking and nonsmoking normal volunteers. The macrophages and monocytes were incubated in vitro with bacterial lipopolysaccharide (LPS). The oxidative metabolic response of these cells was measured by superoxide anion production. Macrophages from smokers were suppressed in their superoxide anion response to LPS activation as compared to macrophages from nonsmokers. Monocytes from smokers and nonsmokers were not different. The cytotoxic properties of these macrophages and monocytes were assessed by an in vitro 3H-thymidine release assay against various allogeneic target cells. Macrophages and monocytes exposed to LPS were rendered tumoricidal. Macrophages from nonsmokers appeared to generate greater cytotoxic activity than macrophages from smokers. Macrophages from both smokers and nonsmokers were cytotoxic for three different tumorigenic cell lines but not for a nontumorigenic cell line. Monocytes from smokers and nonsmokers were not different in cytotoxic activity. We conclude that macrophages from both smokers and nonsmokers can be activated after exposure to LPS; however, macrophages from smokers may be slightly suppressed in their responses.

Adult↗

High prevalence of genital tract papillomavirus infection in female adolescents.

To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.

Adolescent↗

3,5-Diiodotyrosine and thyronine in the urine of patients with chronic renal disease.

Urinary 3,5-diiodotyrosine (DIT) and thyronine (T0) excretion was investigated in 18 patients with chronic renal disease. In accord with previous findings serum T4 and thyroid hormone binding proteins measured in 17 patients were in the low or normal range. Urinary albumin excretion was elevated in all 18 and T4 binding prealbumin (TBPA) in 15 of the 18. Urinary T0 excretion measured in 12 patients was also significantly lower than normal (mean +/- SD 4.4 +/- 2.6 vs 15.8 +/- 5.8 nmol/24 h renal vs normal 2 P less than 0.001). In contrast urinary DIT excretion was significantly elevated in renal patients compared with normal subjects (2.0 +/- 1.5 vs 0.75 +/- 0.41 nmol/24 h, respectively). Possible sources of the increased DIT are discussed.

Adult↗