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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 289 records · Page 16Linked to original sources

Indirect intracranial volume measurements using CT scans: clinical applications for craniosynostosis.

This paper describes a method for obtaining indirect intracranial volume measurements using CT scans with CTpak, a software package for quantitative analysis of CT scan data. The validity of this technique was confirmed by comparing direct measurement of the intracranial volume of five dry skulls with axial scans at 1.5- and 4-mm slice intervals to determine indirect volume. The indirect intracranial volume measurement technique was then used to compare preoperative and postoperative intracranial volume in 30 patients with craniosynostosis who underwent cranial vault and orbital osteotomies with reshaping and advancement. Our findings show that the suture release and simultaneous reshaping procedures usually carried out are, in fact, associated with increased intracranial volume. The observed intracranial volume gain is attributable to a combination of factors, including the surgical procedure carried out and ongoing growth. These factors are further modified by the diagnosis, age of the patient, and time interval between CT scans.

Age Factors↗

Biodistribution and dosimetry following infusion of antibodies labeled with large amounts of 131I.

Dosimetry and treatment planning for therapeutic infusions of radiolabeled antibodies are usually performed by extrapolation from the biodistribution of trace-labeled antibody. This extrapolation assumes that the biodistribution of high specific activity antibody will be similar to that seen with trace-labeled antibody. However, high doses of radiation result in rapid depletion of lymphoid and hematopoietic cells in lymph nodes, spleen, and marrow with replacement by blood and plasma. If radiolabeled antibody is cleared slowly from blood, this replacement may result in increased radionuclide concentrations in these tissues following infusions of antibody labeled with large amounts of radionuclide. To examine the influence of deposited radiation on the biodistribution of radiolabeled antibody, we treated mice with a constant amount of antibody that was labeled with varying amounts of 131I. Survival was determined in normal specific pathogen-free AKR/Cum mice (Thy1.2+) after infusion of anti-Thy1.1 antibody labeled with 10 to 6500 muCi of 131I, to determine an appropriate range of 131I doses for further study. The dose producing 50% lethality within 30 days following infusion of 131I-labeled antibody was 530 muCi 131I. Biodistribution, bone marrow histology, and dosimetry were subsequently determined after infusion of 500 micrograms of antibody labeled with 10, 250, 500, or 3500 muCi 131I. The amount of 131I did not influence uptake or retention of antibody in blood, liver, lung, or kidney. In contrast, infusion of antibody labeled with 250 to 3500 muCi of 131I led to a dose-related increase in the concentration of 131I in marrow, spleen, lymph node, and thymus. For example, at 96 h after infusion of antibody labeled with 500 or 3500 muCi 131I, concentrations in marrow were 3- to 4-fold higher than after infusion of trace-labeled antibody. The increase in marrow 131I concentrations was associated with depletion of cells and hemorrhage within the marrow space. As a result, estimated mean absorbed doses to marrow, lymph node, spleen, and thymus were 1.2 to 3.1 times higher than would have been predicted from the biodistribution of trace-labeled antibody. These results suggest that the biodistribution of trace-labeled antibody should be an accurate predictor of the behavior of high specific activity antibody in blood and solid organs such as liver and kidney. In contrast, radiation from antibody labeled with large amounts of radionuclide can result in an alteration of the concentration of radiolabeled antibody in rapidly responding tissues such as marrow.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Decrease in the risk of bilateral acute retinal necrosis by acyclovir therapy.

We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis.

Acyclovir↗

Serum lipid concentrations in subjects with phenylketonuria and their families.

To determine if subjects with phenylketonuria receiving diets significantly lower in cholesterol and saturated fat had serum lipid concentrations different from those of their family members, we measured serum concentrations of total cholesterol, high-density lipoprotein cholesterol, and total triglycerides in the probands with phenylketonuria, their parents, and their siblings. Eleven adults (seven women and four men) and 16 children (eight girls and eight boys) were studied. Ten subjects (four girls and six boys) had phenylketonuria. Subjects with phenylketonuria consumed less cholesterol (0.02 vs 0.41 mmol/d) and fat (median, 21% vs 39.5% of total calories), and their diets had a higher ratio of polyunsaturated to saturated fatty acids (median, 2.0 vs 0.2) than did their siblings without phenylketonuria. The diet of the parents was similar to that of their offspring without phenylketonuria. No differences were noted between the subjects with phenylketonuria (consuming a diet lower in saturated fat and cholesterol) and their siblings without phenylketonuria in serum concentrations of total cholesterol (median, 3.34 vs 3.07 mmol/L); high-density lipoprotein cholesterol (median, 1.44 vs 1.37 mmol/L); low-density lipoprotein cholesterol (median, 1.44 vs 1.09 mmol/L); or triglycerides (median, 0.89 vs 0.54 mmol/L). We conclude that previously reported lipoprotein abnormalities noted between unrelated subjects with and without phenylketonuria may not be due to differences in dietary intake, but rather due to a (genetic) predisposition of the population with phenylketonuria toward lower serum lipid concentrations.

Adolescent↗

Mammalian ciliary-body epithelial cells in culture produce transforming growth factor-beta.

Transforming growth factor-beta (TGF-beta) has recently been found in the aqueous humor. The present study was initiated to test whether the ciliary-body epithelium, the site of aqueous humor formation, is capable of producing TGF-beta. Human, rat and bovine ciliary epithelial cells were grown in tissue culture and their supernatants were tested for TGF-beta using a bioassay. After acid activation of the samples, TGF-beta activity was found in the supernatants of all three mammalian ciliary epithelial cells. Most of this activity could be blocked by a neutralizing antibody against TGF-beta type 2. Native supernatants did not contain detectable TGF-beta activity. Thus, the ciliary epithelium is capable of producing the inactive form of TGF-beta (mainly type 2) and may be a source of TGF-beta in the aqueous humor.

Animals↗

Fosinopril pharmacokinetics and pharmacodynamics in chronic ambulatory peritoneal dialysis patients.

The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng.ml-1, 4.8 h, and 3.19 micrograms.h.ml-1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng.ml-1, tmax of 9 h, and AUC of 18.1 micrograms.h.ml-1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml.min-1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.

Adult↗

Magnetic resonance imaging in the diagnosis of adolescent colorectal carcinoma.

A 14-year-old girl presented with a large abdominal mass, thought to be an ovarian tumor on the basis of clinical and sonographic findings. MRI correctly suggested a primary colonic neoplasm. At operation, ovarian involvement was found to be secondary to metastatic signet ring cell adenocarcinoma of the colon, an extremely rare malignancy in this age group. Low index of suspicion for this tumor in children and adolescents results in advanced disease at diagnosis and poor prognosis. Early imaging with MRI is recommended when the nature of pelvic disease in children remains obscure.

Adenocarcinoma, Mucinous↗

Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification.

Two human cell lines (UACC-812 and 893), both containing significant amplification of the HER-2/neu gene, were established from biopsy specimens of breast carcinomas. One patient had Stage II breast carcinoma; the other had metastatic disease. Characterisation of these lines has revealed that both are highly aneuploid containing multiple clonal chromosome alterations, have doubling times near 100 h, and are oestrogen and progesterone receptor negative. Electron microscopy demonstrates that both lines contain numerous microvilli, cytoplasmic filaments, multivesicular bodies, and desmosomes. Immunoblot analysis for P-glycoprotein using the monoclonal antibody C219 was negative for both patient cell lines. These relatively rare cell lines may represent a useful model to investigate human breast carcinomas.

Adult↗

Cytotoxic CD4+ T cells from a sporozoite-immunized volunteer recognize the Plasmodium falciparum CS protein.

The present data provide the first evidence that a protozoan parasite, Plasmodium falciparum, can induce CD4+ cytotoxic T cells in man. The CD4+ cytotoxic T lymphocytes (CTL) were derived from a sporozoite-immunized volunteer who was protected against challenge with P. falciparum sporozoites. These T cells recognize an epitope within the circumsporozoite (CS) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vaccine candidate. The class II restricted T cell clones specifically lyse autologous B cells pulsed with a synthetic peptide representing a C-terminal sequence of the P. falciparum CS protein. The same peptide, as well as recombinant or native CS protein, also stimulates proliferation and gamma-interferon production by the CD4+ CTL. The CTL epitope, KIQNSLSTEW, is recognized in the context of HLA-DR7 and overlaps both a highly conserved, as well as a polymorphic, region of the P. falciparum CS protein.

Adult↗

Collaboration as an organizational process.

Successful collaboration does not happen by chance. An understanding of organizations and systems, and planned preventive and corrective actions are needed. These two different experiences with health departments in two different states have helped elucidate the relevant principles and provided examples that may be useful to others in building collaborative research relationships.

Communication↗

Successful immunization of humans with irradiated malaria sporozoites: humoral and cellular responses of the protected individuals.

Two groups of volunteers were vaccinated by repeated exposure to the bites of Plasmodium falciparum-infected, x-irradiated mosquitoes in order to characterize the humoral and cellular immune responses of sporozoite-immunized, protected individuals. One of the two volunteers in the first immunization trial, when challenged by the bite of P. falciparum-infected mosquitoes, developed an infection only after a prolonged prepatent period. A second group of three volunteers who were exposed more frequently to larger numbers of infected mosquitoes irradiated with a lower x-ray dose was completely protected against sporozoite challenge. These individuals and the volunteer with delayed infection had high levels of antibodies to sporozoites and to the repeat region of the circumsporozoite (CS) protein. The CS-specific cellular immune responses of these volunteers were also stimulated by sporozoite immunization, as determined by proliferation of peripheral blood mononuclear cells (PBMC) and mitogen or antigen-expanded PBMC, in response to in vitro challenge with a recombinant P. falciparum CS protein. Based upon the assays used in this study, it is not possible to reach conclusions regarding specific immunologic responses and protection from sporozoite challenge.

Adult↗

Aluminum-citrate interaction in end-stage renal disease.

The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption.

Adult↗