Search PubMed⌕ Search

Biomedical subjects

D E Johnson

Publications and source records attributed to D E Johnson.

At least 343 records · Page 19Linked to original sources

Sutureless end-to-end bowel anastomosis using Nd:YAG and water-soluble intraluminal stent.

Sutureless end-to-end intestinal anastomoses were successfully constructed in 20 rabbits. A water-soluble intraluminal stent was used to approximate the tissue edges, and the anastomotic seam was lased with 1.06 microns neodymium:YAG (Nd:YAG) laser energy supplied through a hand-held 600-microns gas-cooled noncontact optical fiber. A continuous 5-watt wave of power was applied over periods ranging from 46 to 92 seconds to produce the tissue blanching and shrinkage that indicated a satisfactory tissue weld. Integrity, degree of tissue reaction, and bursting pressures of the anastomoses were compared to those of anastomoses constructed using standard sutured techniques. The results of the two methods were equivalent at 1 to 3 days, but the laser-fused enteric anastomoses showed less inflammatory reaction and greater bursting pressures at 7 and 14 days. Application of a variety of proteinaceous solutions including extracellular matrix materials and epidermal growth factors prior to lasing failed to augment wound healing. We conclude that lasers show promise as reconstructive, in addition to ablative, surgical instruments.

Anastomosis, Surgical↗

Superior myocardial preservation with modified UW solution after prolonged ischemia in the rat heart.

Cardiac transplantation remains constrained by poor graft tolerance of prolonged cold ischemia. University of Wisconsin solution has remarkably extended ischemic preservation in pancreas, kidney, and liver transplantation. To assess its efficacy in cardiac preservation, modified University of Wisconsin solution flush and storage were tested against St. Thomas' cardioplegia flush and normal saline solution storage after six hours of ischemia at 0 degrees C in 46 isolated rat hearts. After ischemia, groups were compared before and after reperfusion. After ischemia but before reperfusion, University of Wisconsin solution hearts had significantly less tissue water (3.8%), superior tissue sodium, potassium, calcium, and magnesium profiles, and elevated adenosine and inosine levels, and tended toward better histological preservation. After reperfusion, University of Wisconsin solution more effectively preserved left ventricular compliance (75% versus 35% of baseline), developed pressure (71% versus 45% of baseline), histological integrity, and tissue potassium and calcium profiles than St. Thomas' solution. The University of Wisconsin solution provided superior preservation of systolic and diastolic ventricular function, tissue histology, tissue water, and tissue electrolytes than did St. Thomas' cardioplegia and normal saline solution storage in this experimental model, and might result in improved graft tolerance of ischemia in clinical cardiac transplantation.

Adenine Nucleotides↗

Resistance to Bacillus thuringiensis by the Indian meal moth, Plodia interpunctella: comparison of midgut proteinases from susceptible and resistant larvae.

Midgut homogenates from susceptible and resistant strains of the Indian meal moth, Plodia interpunctella, were compared for their ability to activate the entomocidal parasporal crystal protein from Bacillus thuringiensis. The properties of midgut proteinases from both types of larvae were also examined. Electrophoretic patterns of crystal protein from B. thuringiensis subspecies kurstaki (HD-1) and aizawai (HD-133 and HD-144) were virtually unchanged following digestion by either type of midgut homogenate. Changes in pH (9.5 to 11.5) or midgut homogenate concentration during digestion failed to substantially alter protein electrophoretic patterns of B. thuringiensis HD-1 crystal toxin. In vitro toxicity of crystal protein activated by either type of midgut preparation was equal toward cultured insect cells from either Manduca sexta or Choristoneura fumiferana. Electrophoresis of midgut extracts in polyacrylamide gels containing gelatin as substrate also yielded matching mobility patterns of proteinases from both types of midguts. Quantitation of midgut proteolytic activity using tritiated casein as a substrate revealed variation between midgut preparations, but no statistically significant differences between proteolytic activities from susceptible and resistant Indian meal moth larvae. Inhibition studies indicated that a trypsin-like proteinase with maximal activity at pH 10 is a major constituent of Indian meal moth midguts. The results demonstrated that midguts from susceptible and resistant strains of P. interpunctella are similar both in their ability to activate B. thuringiensis protoxin and in their proteolytic activity.

Animals↗

[125I]-insulin metabolism by the rat liver in vivo: evidence that a neutral thiol-protease mediates rapid intracellular insulin degradation.

The subcellular site where insulin is degraded by rat hepatocytes in vivo is controversial. While several potential insulin-degrading enzyme systems, each with its own characteristic cellular location, are known to exist in the liver, questions remain about which of them participates in the degradation of physiologic doses of insulin. These studies examine the proteases that degrade physiologic doses of [125I]-insulin in vivo to determine (1) when and where initial degradation occurs, and (2) which of the potential degradative enzymes is active. Following injection into the mesenteric veins of male rats, intact [125I]-insulin and its labeled degradation products were analysed by reverse-phase high-performance liquid chromatography (RP-HPLC) of biopsy homogenates. [125I]-insulin was rapidly degraded in vivo; the t 1/2 of degradation was approximately 2.7 minutes. To test for extracellular protease activity, an isolated perfused liver system was employed. [125I]-insulin (or [125I]-glucagon) uptake was controlled by changing the temperature of the perfusion medium. Five minutes after [125I]-insulin injection, surface-bound label was recovered in an acidic (pH 3.5) wash. In perfusion at 15 degrees C, both the internalization and degradation of [125I]-insulin were inhibited; 7.2% of unbound hormone was degraded and 5.1% of surface-bound insulin was degraded. Only 11.4% of unbound insulin and 17.4% of surface-bound insulin were degraded at 35 degrees C. In contrast, 95.5% of unbound glucagon and 89.9% of surface-bound glucagon were degraded at 35 degrees C. Thus, although glucagon degradation occurs at the sinusoidal plasmalemma of perfused livers, the same membrane does not mediate the rapid degradation of insulin observed in vivo. Analysis of the RP-HPLC [125I]-insulin elution profiles from liver biopsy homogenates, and comparison of them to profiles produced by purified proteases, suggested that insulin protease is responsible for most hepatic degradation of physiologic doses of insulin. Some cathepsin D-like activity was also observed in vivo, confirming that two pathways exist for insulin metabolism. The time course over which insulin was degraded was more rapid than previous studies in vitro would have predicted. This suggests that more insulin was receptor-bound at the time of its initial degradation, and that the active protease was soluble and was introduced into endocytic peripheral endosomes within seconds after their formation.

Animals↗

Hyperbilirubinemia after single-stage radical cystectomy and ileal loop diversion.

One hundred ninety-two patients underwent single-stage radical cystectomy and ileal loop diversion over a three-year period. Postoperative hyperbilirubinemia occurred in 21 patients (10.9%) within the first ten days. Early hyperbilirubinemia occurred in 11 patients by postoperative day 5, accounting for 52 percent of the hyperbilirubinemic patients and 5.7 percent of the study population. Elevation persisted into the six to ten-day postoperative period for 9 at which time a total of 18 patients had bilirubin levels elevated above their presurgical values (P less than 0.001). This clinical observation appears to be benign and worthy of further investigation.

Cystectomy↗

Long-term serum creatinine values after radical nephrectomy.

Both pre- and postnephrectomy levels of serum creatinine were measured in 52 consecutive patients who underwent radical nephrectomy for localized renal cell carcinoma between 1971 and 1976. At the time of follow-up, 17 patients were alive and 35 had died, 14 of renal cell carcinoma and 21 of other causes. Follow-up lasted a minimum of 115.5 months (mean 151.1 months, median 141.1, range 115.5-211.3 months) for 16 of the 17 patients who were alive. In this group only 2 patients had elevations in the serum creatinine level above 1.6 mg/dL-1.9 mg/dL and 2.4 mg/dL, respectively. The patient whose value was 2.4 mg/dL was a diabetic who required insulin. No serious renal failure, renal disease, or tumors in the contralateral kidney occurred among the total group of 52 patients. These data indicate that renal function remains adequate in patients who have a normal contralateral kidney and are treated by radical nephrectomy.

Carcinoma, Renal Cell↗

Pelvic lymphadenectomy for staging clinically localized prostate cancer. Indications, complications, and results in 217 cases.

We reviewed the findings of 217 consecutive pelvic lymphadenectomies performed in patients with clinically localized prostatic carcinoma focusing particular attention on the importance of completely removing the hypogastric lymph nodes and on the operative complications associated with a more extensive dissection. Metastatic disease was identified in the lymph nodes of 127 patients (58.6%). The hypogastric nodes were involved in two thirds of the patients with lymph node metastases, and in 29 percent the hypogastric nodes were the only site of metastasis. No increased operative morbidity was documented as a result of extending the level of the pelvic lymphadenectomy to include the lower hypogastric nodes. We conclude that although the lower hypogastric lymph nodes have not been routinely included in most pelvic lymphadenectomies, their removal is important in detecting metastases.

Adenocarcinoma↗

Squamous cell carcinoma antigen (TA-4) in penile carcinoma.

TA-4 antigen, originally isolated from women with squamous cell carcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites, including esophagus, lungs, and head and neck. In this study, we compared the serum levels of TA-4 in normal volunteers, patients with resected penile squamous cell carcinoma, and patients with metastatic penile squamous cell carcinoma. TA-4 values were elevated in 5 of 11 patients (45%) who had metastatic disease. In 2, TA-4 was normal the first time metastasis was clinically detected but rose as the disease progressed. Moreover, in 3 patients in whom serial determinations were made, serum TA-4 values correlated well with disease progression and response to treatment. We conclude that TA-4 values are elevated in some patients with metastatic squamous cell carcinoma of the penis and may become a useful marker for monitoring response to therapy.

Antigens, Neoplasm↗

Indications for urethrectomy in an era of continent urinary diversion.

Interest in performing a continent urinary diversion and in preserving sexual potency after radical cystectomy for transitional cell carcinoma of the bladder has emphasized the need to identify accurately those men who are at high risk for urethral recurrences. We reviewed the records of 200 men who underwent radical cystectomy between 1969 and 1976. In 76 men urethrectomy and cystectomy were combined. Of these patients 6 had known urethral tumors and the incidence of unsuspected urethral malignancy was 2.9%. A total of 124 men had initial cystectomy only and were monitored up to 16 years (mean 67 months). Of these patients 6 (4.8%) underwent subsequent urethrectomy for malignant disease 6 to 40 months (median 23.5 months) after cystoprostatectomy. This group included 1 of 69 patients (1.5%) who presented with a solitary tumor not encroaching on the bladder neck, 1 of 22 (4.5%) with either carcinoma in situ or multifocal tumors not involving the prostate and none of the 9 with tumor at the bladder neck alone, which suggests that these patients may be satisfactory candidates for continent urinary diversion and may avoid the added risk to potency associated with urethrectomy. However, urethral recurrences were found in 4 of 24 patients (17%) who presented with disease extending into the prostate, including 3 of 10 (30%) with stromal invasion. These results emphasize the importance of assessing the prostatic urethra and ducts carefully before deciding to eliminate urethrectomy.

Carcinoma, Transitional Cell↗

Familial renal cell carcinoma: hereditary or coincidental?

The familial clustering of some cancers may be related to genetic factors, shared carcinogenic exposure among relatives or chance association. In cases of familial renal cell carcinoma identifying those persons at risk for renal tumors is difficult. There have been 28 family aggregates of renal carcinoma reported since 1961 but an abnormality in the constitutional karyotype has been demonstrated in the members of only 1 of these families. Since 1980 we have identified 5 more families in which a total of 12 relatives had renal cell carcinoma. However, peripheral blood karyotypes obtained from the 7 patients and 5 unaffected relatives whom we studied showed no significant abnormalities. With current laboratory techniques it is not possible to differentiate reliably familial renal tumors occurring by chance from those hereditary tumors posing a threat to remaining relatives. Therefore, in families with multiple cases of renal cell carcinoma we recommend that screening be conducted as has been suggested for families with von Hippel-Lindau's disease, with an initial renal ultrasound for family members at age 30 years and repeat examinations every 2 to 3 years.

Adult↗

Primary peripheral arterial stenoses and restenoses excised by transluminal atherectomy: a histopathologic study.

Atherectomy is a new therapeutic intervention for the treatment of peripheral arterial disease, and permits the controlled excision and retrieval of portions of stenosing lesions. The gross and light microscopic features of 218 peripheral arterial stenoses resected from 100 patients by atherectomy were studied. One hundred seventy of these lesions were primary stenoses and 48 were restenoses subsequent to prior angioplasty or atherectomy. Microscopically, primary stenoses were composed of atherosclerotic plaque (150 lesions), fibrous intimal thickening (15 lesions) or thrombus alone (5 lesions). Atherosclerotic plaques had a variable morphology and, in one-third of cases, were accompanied by abundant surface thrombus that probably added to the severity of stenosis. Most patients with fibrous intimal thickening or thrombus alone had typical atherosclerotic plaque removed elsewhere from within the same artery. Intimal hyperplasia, with or without underlying residual plaque, was found at 36 sites of restenosis, the remaining 12 consisting of plaque only. Intimal hyperplasia had a distinctive histologic appearance and was due to smooth muscle cell proliferation within a loosely fibrous stroma. Superimposed thrombus may have contributed to arterial narrowing in 25% of hyperplastic and 8% of atherosclerotic restenoses (p = 0.41). Pathologic examination of tissues recovered by peripheral atherectomy is an important adjunct that may provide insight into the efficacy of vascular interventions and the phenomenon of postintervention restenosis.

Adult↗

Directional peripheral atherectomy: histopathologic aspects of a new interventional technique.

Among the new transluminal vascular interventions currently being explored, directional atherectomy is unique in that it improves vessel patency by resecting intact portions of atherosclerotic plaque. Experimental atherectomy studies show that strips of plaque are cut away, leaving behind confluent defects within the stenotic lesions. Histologic examination of tissues excised during clinical peripheral atherectomy documents the heterogeneous morphology of peripheral atherosclerosis and shows that intimal hyperplasia is the most common cause of restenosis after therapeutic vascular interventions.

Arteriosclerosis↗

Changes in liver and gastrointestinal tract energy demands in response to physiological workload in ruminants.

Liver and gastrointestinal tract weights (ingesta- and adipose-free) appear to increase or decrease in direct proportion to dietary intake within and across physiological stages of maintenance, growth, fattening or lactation. Liver and gut mass increase approximately 15 and 30 g per unit of liveweight raised to the 0.75 power (Wt0.75) for each multiple of 500 kJ/Wt0.75 [approximately 1 x maintenance (M)] increase in metabolizable energy (ME) intake, with linearity indicated up to the highest recorded level (4.5 x M). Extrapolation from in vivo arteriovenous O2 measurements across splanchnic tissues and from the previously cited weight information indicates that liver and gut tissue oxidize approximately 3.5 and 1.0 kJ of ME/g of fresh tissue daily, in contrast to whole-animal rates of 0.1 kJ/g. Thus, energy use by the relatively small amount of liver and gut accounts for 45 to 50% of whole-animal heat energy. On a differential basis, increases in energy use by these tissues appear to account for up to 70% of the heat increment of ME use above maintenance.

Animal Nutritional Physiological Phenomena↗

Prompt orchiectomy reduces morbidity and mortality from testicular carcinoma.

The records of 154 patients with non-seminomatous germ cell testicular tumours were reviewed to determine the potential effect of prompt diagnosis and orchiectomy on morbidity and mortality from this disease. Orchiectomy was performed 30 days or less after the onset of testicular symptoms on 65 patients (Group 1) and more than 30 days after the onset of symptoms on 89 patients (Group 2). The initial clinical stages of Group 1 patients were: I, 40 (62%); II, 14 (22%); III, 5 (8%); marker only, 6 (9%). The initial clinical stages for Group 2 patients were: I, 25 (28%); II, 15 (17%); III, 35 (39%); marker only, 14 (16%). The difference between the percentages of Group 1 and Group 2 patients with stage I disease was statistically significant, as was the difference between the percentages of Group 1 and Group 2 patients with stage III disease. One of the Group 1 patients died, whereas 11 of the Group 2 patients died. In 5 of the Group 2 patients who died, orchiectomy had been performed more than 120 days after the onset of testicular symptoms. This study suggests that orchiectomy performed promptly after the onset of testicular symptoms not only helps to reduce mortality from testicular cancer but also has a major effect on its morbidity by reducing the need for systemic chemotherapy or major surgery.

Humans↗

An external urine collection device for incontinent women. Evaluation of long-term use.

Urinary incontinence is common in aged women, may precipitate nursing home admission, and may prompt use of a urine collection device, usually an indwelling urethral catheter. The safety and efficacy of a new external urine collection device for women that is affixed to the perineum by an adhesive developed for ostomy bags was evaluated. Applied to 26 aged women, 78% of 2,264 devices were leak-free for 24 hours and 49% for 48 hours. The incidence of new bacteriuria was less than half that found in our earlier studies of long-term urethral catheters in the same institution. Perineal erythema was infrequent and preexisting decubitus ulcers improved or did not change. Four patients were withdrawn, one each because of periurethral itching, diminished urine output, recurrent wetness, and fracture of the proximal femur associated with severe osteoporosis. This device may offer an alternative to urethral catheters for management of urinary incontinence but should not be used on women with urine retention and should be used with care on women with severe osteoporosis. Controlled trials must determine effects upon bacteriologic complications and health-care costs.

Aged↗

Construction of a urease-negative mutant of Proteus mirabilis: analysis of virulence in a mouse model of ascending urinary tract infection.

Proteus mirabilis, a urease-producing uropathogen, causes serious urinary tract infections in humans. To specifically evaluate the contribution of urease to virulence, a mutation was introduced into P. mirabilis HI4320 by homologous recombination. Virulence was assessed in the CBA mouse model of ascending urinary tract infection. Twenty mice each were challenged transurethrally with P. mirabilis HI4320 and its urease-negative derivative (1 x 10(9) to 2 x 10(9) CFU). At 48 h animals were sacrificed and the mean log10 CFU per milliliter of urine (parent, 6.23; mutant, 4.19; P = 0.0014) or per gram of bladder (parent, 6.29; mutant, 4.28; P = 0.0002), left kidney (parent, 4.11; mutant, 1.02; P = 0.00009), and right kidney (parent, 4.11; mutant, 2.43; P = 0.036) were all shown to be significantly different. These data demonstrate a role for urease as a critical virulence determinant for uropathogenic P. mirabilis.

Animals↗

Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains.

Acute pyelonephritis, a complication of Escherichia coli bacteriuria, must represent a bacterial invasion through the kidney epithelium. To study this process, we overlaid bacterial suspensions onto monolayers of cultured human kidney proximal tubular epithelial cells and measured cytotoxicity by release of lactate dehydrogenase (LDH). Thirty-four isolates cultured from patients with acute pyelonephritis were screened for the ability to cause pyelonephritis in CBA mice by transurethral challenge. The eight most virulent strains (greater than or equal to 70% of mice challenged developed greater than or equal to 10(3) CFU/g of kidney after 48 h) were selected for study. Each strain displayed mannose-resistant hemagglutination of human O erythrocytes; three strains were phenotypically and genotypically hemolytic. Pyelonephritogenic strains were significantly more cytotoxic (30.1 +/- 9.5% LDH release after 18 h) than eight fecal control strains (13.5 +/- 11.5% LDH release; P = 0.0068). We selected the most cytotoxic strain, CFT073, for further study. Sterile filtrate from this hemolytic strain was significantly more cytotoxic than was the filtrate of the fecal control strain, FN414. Transposon mutagenesis of CFT073 with TnphoA abolished hemolytic activity and cytotoxicity by both whole cells and sterile filtrate. Southern blot analysis revealed that the Tnphoa insertion mapped to the E. coli chromosomal hly determinant within a 12-kilobase SalI restriction fragment. Transformation of a nonhemolytic strain, CPZ005 with plasmid pSF4000, which carries a cloned hemolysin determinant, resulted in highly elevated cytotoxicity. Light micrographs of proximal tubular epithelial cell cultures demonstrated cell damage by pyelonephritogenic strains that was not induced by a fecal strain or the hemolysin-deficient mutant. Results indicate that pyelonephritogenic E. coli strains are more frequently cytotoxic for a putative target, that is, human renal tubular epithelium, than are fecal isolates. Hemolysin, in some strains, is apparently responsible for this cytotoxicity.

Bacterial Toxins↗