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Biomedical subjects

W H Fleming

Publications and source records attributed to W H Fleming.

At least 37 records · Page 2Linked to original sources

Intrapleural doxycycline control of malignant pleural effusions.

The intrapleural instillation of agents for pleural sclerosis has proved effective in preventing the reaccumulation of symptomatic malignant pleural effusions. Because manufacture of the most popular agent, tetracycline, was recently discontinued, a preliminary study was undertaken to evaluate an alternative agent, doxycycline, for treating symptomatic malignant pleural effusions. From November 1991 to September 1992, 21 patients with symptomatic malignant pleural effusions have undergone overnight chest tube drainage followed by intrapleural instillation of 10 mL 1% lidocaine and then doxycycline, 500 mg in 30 mL 0.9% saline solution. The chest tube was clamped 2 hours with patient repositioning every 15 minutes. Tubes were removed when drainage was less than 50 mL/8 h. Of surviving patients, a complete objective response at 1 month was obtained in 88% (15/17), who were free of a symptomatic or radiographic recurrence of the effusion. Complications included mild pain in 23% (5/21), moderate pain requiring analgesics in 19% (4/21), and mild fever in 5% (1/21). There were no treatment-related deaths. The mean time for chest tube removal was 1.7 +/- 0.7 days after the last treatment. Based on this preliminary study, we conclude that doxycycline is a highly effective agent for the palliative treatment of symptomatic malignant pleural effusions. Its safety profile and efficacy compare favorably with those of tetracycline and other agents used for pleural sclerosis.

Adult↗

Heterogeneity of hematopoietic stem cells.

Hematopoietic stem cells are capable of multi-lineage differentiation to all blood cell types as well as self-renewal and radioprotection. Thy-1.1lo Lin-/lo Sca-1+ cells are a heterogeneous mixture of quiescent and self-renewing hematopoietic stem cells as well as multi-lineage expanding cells.

Animals↗

Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy1.1lo Lin-/lo Sca-1+) that contain > 2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [3H]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in G0/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in G0/G1. The injection of 100 G0/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donor-derived multilineage reconstitution of the peripheral blood was observed in recipients of 100 G0/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity.

Animals↗

Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. A prospective study.

We assessed the morphologic findings of the brain prospectively before and after cardiac surgery using magnetic resonance imaging. There were 12 patients with acyanotic and 6 with cyanotic heart disease. There were 2 deaths, and 1 patient did not have to undergo postoperative magnetic resonance imaging. The study group consisted of 15 patients completing both the preoperative and postoperative magnetic resonance imagings. All patients in the study group underwent moderate hypothermic cardiopulmonary bypass using a nonpulsatile membrane oxygenator. The mean (+/- SD) cardiopulmonary bypass time was 100 +/- 55 minutes. Ten of the preoperative studies were interpreted as normal. One third (5 of 15) of the patients showed ventriculomegaly and dilatation of the subarachnoid spaces on preoperative magnetic resonance images. Measurements of the preoperative and postoperative magnetic resonance images showed a postoperative increase in the bicaudate and third ventricular diameters. Four patients in the study group developed postoperative subdural hematomas. The subdural hematomas were small and caused no demonstrable mass effect on magnetic resonance imaging. One patient had a preoperative white matter infarction. There was 1 patient with a postoperative infarction.

Brain↗

Omphalocele associated with coronary sinus atrial septal defect: report of two cases.

Two children with omphalocele were found to have coronary sinus atrial septal defect as part of their congenital heart disease complex. This unusual atrial communication may elude preoperative detection unless specifically sought. Its occurrence in conjunction with omphalocele may represent more than a chance association.

Abnormalities, Multiple↗

Valve replacement in the right side of the heart in children: long-term follow-up.

Twenty-five patients (16 male, 9 female) underwent right-sided valve replacement (10 pulmonary valve replacement, 14 tricuspid valve replacement, 3 tricuspid plus pulmonary valve replacement, and 2 replacements of a single atrioventricular valve) at the University of Nebraska Medical Center from June 1977 to December 1986. Twenty-one patients (84%) are long-term survivors with 2,035 months follow-up (range, 41 to 143 months; mean, 96.9 months). Twenty-three Carpentier-Edwards bioprosthetic valves, one Ionescu-Shiley bioprosthetic valve, and nine St. Jude Medical valves were inserted. Follow-up of 17 patients with a Carpentier-Edwards valve ranged from 5 years 9 months to 11 years 9 months (mean, 8 years 11 months). To date there has been one reoperation after 3 years 4 months in this group. One patient who received an Ionescu-Shiley bioprosthesis required re-replacement at 20 months after operation. Three of 4 patients who received St. Jude mechanical valves and are long-term survivors have required replacement after 36 to 56 months. We conclude that the Carpentier-Edwards bioprosthetic valve is a viable option in the right side of the heart in the young age group when annular size is adequate to accommodate an appropriate bioprosthesis.

Adolescent↗

Retraction of bioprosthetic heart valve cusps: a cause of wide-open regurgitation in right-sided heart valves.

Most failures of bioprosthetic heart valves in children are due to stenosis secondary to thrombus, calcific deposits, or tissue ingrowth. Valve failures due to regurgitation typically involve cuspal detachment, tears, or perforations. We present four cases of prosthetic valve regurgitation in children caused by cuspal retraction without stenosis and describe the morphologic findings related to the valves at autopsy or explantation. A mononuclear cell and giant cell response to the cusps of the valve was a striking finding in one patient.

Adolescent↗

Evaluation of SOC for the presumptive identification of Candida albicans and Cryptococcus neoformans.

SOC, a fungal growth medium composed of Solryth, oxgall, and caffeic acid, was evaluated as a medium to provide rapid, differential identification of Candida albicans and Cryptococcus neoformans. Using a variety of common isolation media to produce the yeast inocula, the germ tube methods tested ranked in the following order of decreasing sensitivity: SOC (97% +/- 1), serum (92% +/- 5), rabbit coagulase plasma with EDTA in combination with tryptic soy broth (89% +/- 5), TOC (89% +/- 6), and rabbit coagulase plasma with EDTA (83% +/- 4). In chlamydospore production, SOC also proved to be the most sensitive after 24 h incubation: SOC (96% +/- 2), TOC (80% +/- 2), and cornmeal-Tween 80 agar (14% +/- 3). Other medically important yeasts showed normal patterns of growth within 24 h on SOC, thus assisting in their identification. Eighty strains of Cryptococcus neoformans showed characteristic brown pigmentation on SOC and TOC within 18 h, while all other species of the genus Cryptococcus and 229 Candida isolates did not show a change in pigmentation.

Candida albicans↗

Aortic valve replacement with concomitant aortoventriculoplasty in children and young adults: long-term follow-up.

Sixteen patients (9 male, 7 female) underwent aortic valve replacement (AVR) with a Konno aortoventriculoplasty at the University of Nebraska Medical Center from August, 1976, to May, 1986. There was 1 early death (6%), but no operative deaths have occurred since 1977. There was 1 late death from unknown cause 51 months postoperatively. One patient has been lost to follow-up. Long-term follow-up of 14 patients was 923 months (mean, 66 months; range, 9 to 120 months). Of the 16 patients, 12 (75%) had had previous cardiovascular procedures. A total of thirty-five operations, including the aortoventriculoplasties, were done in the 16 patients. Of the aortic valves inserted, 11 were tissue valves (Carpentier-Edwards, 10; Ionescu-Shiley, 1) and 5 were mechanical valves (St. Jude, 3; Björk-Shiley, 2). Patient age at the time of aortoventriculoplasty ranged from 2 years 3 months to 24 years (median, 11 years 8 months). Size of the aortic annulus ranged from 10 to less than 21 mm (median, 16 mm). Valves inserted ranged from 21 to 29 mm; 13 (81%) of them were 25 mm or larger. In 2 patients, degenerated tissue valves were replaced with mechanical valves after 110 and 33 months. At present, all patients are in New York Heart Association Functional Class I. One female patient married and delivered a normal child approximately five years after AVR with a Carpentier-Edwards valve plus aortoventriculoplasty; she never received anticoagulant medications. We conclude that AVR with a concomitant Konno aortoventriculoplasty can be safely performed in the pediatric and young-adult age groups with satisfactory results for up to ten years.

Adolescent↗

Postnatal atresia of extraparenchymal pulmonary veins, fulminant necrotizing pulmonary arteritis and elevated circulating immune complexes.

An infant with operatively corrected total anomalous pulmonary venous connection developed postnatal atresia of the extraparenchymal left pulmonary veins with secondary arteritis of the ipsilateral intraparenchymal pulmonary arteries. Atresia of the right or left main pulmonary veins or of the common pulmonary vein is a rare occurrence and it is believed that association of such with necrotizing pulmonary arteritis has never been reported. This case illustrates the potential consequences of severe pulmonary venous obstruction in the absence of a left to right shunt.

Angiography↗

Regulation of prostatic genes: role of androgens and zinc in gene expression.

Gene expression in the rat dorsolateral prostate gland has been studied using cloned cDNA probes to the most abundant expressed mRNAs. One cDNA clone (pM-40) corresponds to two closely homologous mRNAs of about 880 nucleotides which code for two proteins of 23 and 21 kilodaltons (kDa). At least the 23-kDa protein contains a signal peptide. Another clone (pRWB) corresponds to a 1550-nucleotide mRNA which codes for a 52-kDa protein which also contains a signal peptide. The steady-state levels of these specific mRNAs increase in the dorsolateral prostate with sexual maturation. In castrated mature male rats, the M-40 mRNAs are inducible either by androgens or zinc, while the RWB mRNA is only responsive to androgens. In situ cDNA-mRNA hybridization histochemistry has been used to study the localization of the M-40 and RWB gene transcripts. Both M-40 and RWB mRNAs are most abundant in the epithelium of the lateral tip of the dorsolateral prostate. Following castration, the RWB mRNA decreases, while the M-40 mRNAs continue to be expressed in isolated areas of the epithelium. These castration-resistant cells maintain normal morphology in the absence of androgens.

Androgens↗

Expression of the c-myc protooncogene in human prostatic carcinoma and benign prostatic hyperplasia.

We have examined the level of c-myc transcripts in prostate tissue obtained from patients with both benign prostatic hyperplasia and adenocarcinoma of the prostate. A significantly higher level of c-myc transcripts is observed in patients with adenocarcinoma (P less than 0.05). In addition, a subset of patients with adenocarcinoma had levels of c-myc transcripts 2-fold higher than the mean level for this group. These preliminary results indicate that the investigation of c-myc levels as a prognostic indicator in prostatic carcinoma is warranted.

Acid Phosphatase↗

Serum concentrations of prostacyclin and thromboxane in children before, during, and after cardiopulmonary bypass.

Twenty-six consecutive pediatric patients undergoing reparative procedures necessitating cardiopulmonary bypass were prospectively studied to determine changes in serum levels of 6-keto-prostaglandin F1 alpha and thromboxane B2. Cardiac lesions included acyanotic lesions (five patients), obstructive lesions (10 patients), and right-to-left shunts (11 patients). There was a significant (p less than 0.05) increase in 6-keto-prostaglandin F1 alpha from preoperative levels measured at the time of arterial and venous cannula insertion. This concentration was maintained throughout cardiopulmonary bypass and remained significantly elevated (p less than 0.001) in the recovery room, but returned to preoperative levels by the morning after the operation. Preoperative levels of thromboxane B2 varied widely and were not significantly different from intraoperative levels. The postoperative levels of thromboxane B2, however, were significantly different (p less than 0.05) from the intraoperative levels. In the pediatric age group undergoing cardiopulmonary bypass, 6-keto-prostaglandin F1 alpha and thromboxane B2 change during bypass but do not significantly differ when preoperative levels are compared to postoperative values.

6-Ketoprostaglandin F1 alpha↗