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Biomedical subjects

D M Kelly

Publications and source records attributed to D M Kelly.

At least 19 recordsLinked to original sources

Detection of glass patterns by pigeons and humans: implications for differences in higher-level processing.

Glass patterns have been used to examine mechanisms underlying form perception. The current investigation compared detection of Glass patterns by pigeons and humans and provides evidence for substantial species differences in global form perception. Subjects were required to discriminate, on a simultaneous display, a random dot pattern from a Glass pattern. Four different randomly presented Glass patterns were used (concentric, radial, parallel-vertical, and parallel-horizontal). Detection thresholds were measured by degrading the Glass patterns through the addition of random noise. For both humans and pigeons, discrimination decreased systematically with the addition of noise. Humans showed detection differences among the four patterns, with lowest thresholds to radial and concentric patterns and highest thresholds to the parallel-horiZontal pattern. Pigeons did not show a detection difference across the four patterns. Implications for differences in neural processing of complex forms are discussed.

Adult↗

Pigeons encode relative geometry.

Pigeons were trained to search for hidden food in a rectangular environment designed to eliminate any external cues. Following training, the authors administered unreinforced test trials in which the geometric properties of the apparatus were manipulated. During tests that preserved the relative geometry but altered the absolute geometry of the environment, the pigeons continued to choose the geometrically correct corners, indicating that they encoded the relative geometry of the enclosure. When tested in a square enclosure, which distorted both the absolute and relative geometry, the pigeons randomly chose among the 4 corners, indicating that their choices were not based on cues external to the apparatus. This study provides new insight into how metric properties of an environment are encoded by pigeons.

Animals↗

Pulmonary lymphangitis carcinomatosa and acute pancreatitis: a rare presentation of choledochal cyst.

Pulmonary lymphangitis carcinomatosa is an unusual cause of death in a young adult. This case describes an apparently healthy young woman who presented with severe acute pancreatitis, which is a recognized complication of a choledochal cyst. Autopsy examination revealed advanced malignancy with poorly differentiated adenocarcinoma penetrating the wall of the choledochal cyst and metastatic adenocarcinoma in the lymph nodes, lungs and kidneys. This case emphasises the unusual presentation of a choledochal cyst with acute pancreatitis and the aggressive nature of malignancy associated with this congenital anomaly.

Acute Disease↗

Liver transplant recipients are not at increased risk for nonlymphoid solid organ tumors.

BACKGROUND: Organ transplant recipients are at higher risk for developing lymphoid tumors, skin carcinomas, and sarcomas. Whether liver transplant recipients are at higher risk for developing more common cancers is unclear. METHODS: All patients with a history of malignancy prior to liver transplantation and those who developed malignancy, either de novo or recurrent, after transplantation were identified retrospectively. The following parameters were examined: age at diagnosis; indication for transplant; interval from transplant to tumor diagnosis; tumor treatment received; predisposing factors for the development of cancer; immunosuppression regimen, including the use of OKT3; number and treatment of rejection episodes; and survival. RESULTS: Of 888 patients, 29 (3.2%) had 31 previous malignancies; of these 29 patients, 4 developed a recurrence in the posttransplant period. Thirty-nine patients (4.3%) developed 43 de novo nonlymphoid malignancies. Alcoholic cirrhotic patients had a significantly higher incidence of de novo carcinomas. Except for skin carcinomas, tumors did not occur with greater frequency than in the general population, and recurrent tumors were not more aggressive than reported for that disease. One patient had an unrecognized renal cell carcinoma at the time of transplant that progressed rapidly; this patient died 64 days after transplantation. CONCLUSIONS: With current immunosuppressive regimens, liver transplant patients do not appear to be at an increased risk for developing nonlymphoid solid organ tumors. However, longer follow-up will be necessary to confirm these results.

Adult↗

Spontaneous rupture of a malignant rhabdoid tumour of the liver.

Malignant rhabdoid tumours (MRT) of the liver are rare. The criteria for pathological diagnosis are clearly defined, but the clinical behaviour of these tumours is still emerging. We report a MRT of the liver with the rare clinical presentation of spontaneous rupture.

Combined Modality Therapy↗

Safe use of hepatic allografts from donors older than 70 years.

Between March 1991 and August 1995, 36 livers from donors >/=70 years old were transplanted. In donors, we recorded the following risk factors: alanine aminotransferase > 120 and rising, dopamine dose > 15 microg/kg/min, hypotension (systolic blood pressure <80) >1 hr, stay in the intensive care unit >5 days and body mass index >/=27. In 35 recipients, we recorded pretransplant United Network for Organ Sharing (UNOS) status, cold/warm ischemia time, intraoperative blood loss, and occurrence of poor early graft function or primary nonfunction. Mean recipient age was 55 years (range, 25-75 years). Four recipients were UNOS status 1, 19 were UNOS 2, and 12 were UNOS 3. Two livers were used as second grafts for primary graft nonfunction. Mean donor age was 73 years (range, 70-84 years). Intracranial bleeding was the cause of death in the majority of donors. The 36 donors had 40 risk factors; 10 donors had >1 risk factor. Mean cold and warm ischemia times were 9:08 +/- 2:57 hr and 51 +/- 9 min. Mean total operative time was 7.5 hr. Posttransplant mean peak alanine aminotransferase and aspartate aminotransferase levels were 937.3 +/- 703.1 IU/L and 923.3 +/- 708.5 IU/L, respectively. Mean prothrombin time on postoperative day 2 was 14.9 +/- 1.6 sec. Average total bilirubin on postoperative day 5 was 4.9 mg/dl. Median length of stay in the intensive care unit was 4 days. One recipient had poor early graft function; two recipients had primary nonfunction. Mean follow-up was 503 days (range, 110-1714 days). Three-month actual graft and patient survival rates were 85% and 91%, respectively. One-year actuarial graft and patient survival rates were also 85% and 91%, respectively. We conclude that older livers can be used safely. Advanced donor age should not be a contraindication to liver procurement.

Adult↗

Revised approach for identification and detection of ampicillin and vancomycin resistance in Enterococcus species by using MicroScan panels.

The frequency of antimicrobial agent-resistant enterococci is increasing, making accurate identification and screening for susceptibility essential. We evaluated the ability of MicroScan Positive Breakpoint Combo Type 6 panels (Dade MicroScan Inc., West Sacramento, Calif.) to identify Enterococcus species and to detect ampicillin and vancomycin resistance. A total of 398 well-characterized Enterococcus isolates from two institutions were inoculated into MicroScan panels, into conventional biochemical assays, and into ampicillin and vancomycin agar dilution media. Resistance was verified by the broth macrodilution method. MicroScan panels accurately detected resistance to ampicillin in 132 of 132 enterococcal isolates, while three isolates for which the MICs were < 16 micrograms/ml were classified incorrectly by MicroScan panels as resistant. No beta-lactamase-producing enterococci were detected. All 64 isolates showing resistance to vancomycin (MICs > or = 32 micrograms/ml) were correctly classified by MicroScan panels. Seven isolates for which the vancomycin MICs were 8 and 16 micrograms/ml were incorrectly classified as susceptible by MicroScan panels, while eight isolates for which the MICs were 4 micrograms/ml were incorrectly labeled as intermediate. Fourteen of these 15 isolates were subsequently identified as motile enterococci. Overall, there were three major errors in susceptibility testing for ampicillin and 15 minor errors for vancomycin. Conventional testing confirmed the identity of 181 Enterococcus faecalis isolates, 157 E. faecium isolates, and 60 isolates of other species; however, 56 of these 60 isolates were misidentified by the MicroScan panels. After recognition of this problem, a revised approach which included tests for pigment, motility, and sucrose fermentation was devised. In combination with these additional assays, the conventional MicroScan panels accurately identified the 56 originally misidentified isolates. In summary, the ability of MicroScan panels to detect vancomycin and ampicillin resistance in enterococci was confirmed. Our study found that the inability of MicroScan panels to identify enterococci other than E. faecalis and E. faecium can be compensated for by the addition of standard assays.

Ampicillin Resistance↗

Effect of off-site transportation on detection of Neisseria gonorrhoeae in endocervical specimens.

OBJECTIVES: To evaluate both the effect of off-site transportation on detection of Neisseria gonorrhoeae in cultured endocervical specimens and the impact of transportation on viability of N. gonorrhoeae by comparison of culture with a nucleic acid probe assay. DESIGN: Three endocervical swabs were randomly collected; one was tested on-site using a nucleic acid-based assay (PACE 2NG System, Gen-Probe, Inc, San Diego, Calif), one was tested off-site following inoculation to modified Thayer-Martin agar (Remel, Lenexa, Kan), and a third swab was tested on-site by culture isolation. A nucleic acid amplification assay of the original swab for PACE 2NG testing was used to resolve discrepancies. SETTING: The emergency department of a university medical center. PATIENTS: Four hundred two patients were evaluated. The test population consisted of both asymptomatic and symptomatic patients. MAIN OUTCOME MEASURE: Positivity for N. gonorrhoeae by one or more of the test procedures, with discrepancy analysis when warranted. RESULTS: Of 402 specimens evaluated, the sensitivities for on-site and off-site testing using culture isolation for N. gonorrhoeae were 88.9% and 77.8%, respectively, in a population prevalence of 6.7%. However, the sensitivity for on-site PACE 2NG testing for N. gonorrhoeae was 96.3%. CONCLUSIONS: A decrease in sensitivity between on-site and off-site culture was found, which suggested transportation may have an adverse effect on the detection of N gonorrhoeae. However, with the limited population and prevalence, the difference was not found to be statistically significant. Further studies indicated that the nucleic acid probe assay was significantly more sensitive (P = .05) when compared with off-site testing using a culture isolation method, demonstrating that viability is an important consideration. These results suggested that a molecular probe assay should be considered in testing specimens for N. gonorrhoeae, especially when the specimen is to be transported off-site.

Bacteriological Techniques↗

Invasive infection due to Candida krusei in immunocompromised patients not treated with fluconazole.

Candida krusei is a cause of invasive candidiasis (IC), with numerous cases reported among leukemia patients after bone marrow transplantation and treatment with fluconazole. The relation between fluconazole therapy and IC remains controversial. In a retrospective review covering 5 years, we identified 203 cases of IC, 71 (35%) of which were due to non-albicans species. Eight cases were caused by C. krusei: four of the patients involved had leukemia, two had breast cancer, one had end-stage liver disease, and one had undergone abdominal trauma. None of these patients received fluconazole. Surveillance cultures detected colonization with C. krusei before the onset of symptoms in seven cases. The median time from colonization to IC diagnosis was 10 days. Of six patients with neutropenia, five were neutropenic at IC diagnosis. Concomitant infections were common; four patients had both bacteremia and invasive aspergillosis. C. krusei was considered the immediate cause of five of the seven deaths among this group of patients. These eight cases extend the range of immunocompromised conditions in which IC caused by C. krusei develops in the absence of fluconazole therapy.

Abdominal Injuries↗

Pancreatic carcinoma.

The management of patients with pancreatic carcinoma poses many problems. The diagnosis is usually made late, generally because the patients present late, but it is not unusual to find patients who have had many negative investigations for vague upper abdominal symptoms only to be diagnosed as having pancreatic carcinoma many months later. Staging the disease is equally difficult and often inaccurate. The results of treatment are to date discouraging even in those patients diagnosed early. But the outlook is not totally dismal; in recent years the results for surgical resection of pancreatic lesions have improved; adjuvant treatment may finally be having an effect, although small, on this relentless disease. The most notable inroad made in the management of pancreatic cancer in the last 10 years is the improvement in palliation due to the use of the endoprosthesis. In spite of the poor results we must continue to search actively for more accurate methods of diagnosis and better methods of treatment.

Antigens, Neoplasm↗

Evaluation of nucleic acid-based test (PACE 2C) for simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae in endocervical specimens.

A nucleic acid-based test (Gen-Probe PACE 2C System) was evaluated for the ability to detect Chlamydia trachomatis and Neisseria gonorrhoeae from endocervical specimens in a single assay. Three swab samples, randomized for collection order, were obtained from each patient and tested by N. gonorrhoeae and C. trachomatis culture and by the PACE 2C probe assay. Fifty of 395 specimens were culture positive for N. gonorrhoeae (17 specimens), C. trachomatis (26 specimens), or both (7 specimens), of which PACE 2C testing detected 48 specimens. The PACE 2C assay was positive for 56 specimens, including 8 specimens not positive by culture. Of the total of 10 discrepancies between culture and PACE 2C results, resolution testing yielded four false-negative culture, four false-positive PACE 2C, and two false-negative PACE 2C results. The sensitivity, specificity, and positive and negative predictive values for PACE 2C after reevaluation were 96.3, 98.8, 92.9 and 99.4%, respectively. The overall sensitivities for C. trachomatis and N. gonorrhoeae culture were 89.2 and 88.9%, respectively. The prevalence rate for C. trachomatis was 9.4%, and that for N. gonorrhoeae was 6.8%. The Gen-Probe PACE 2C System is a reliable alternative for screening endocervical specimens for both C. trachomatis and N. gonorrhoeae in a single assay.

Cervix Uteri↗

Glomerular epithelial and mesangial cells differentially modulate the binding specificities of VLA-1 and VLA-2.

BACKGROUND: Maintenance of glomerular cell interaction with the complex basement membrane is crucial for the normal functioning of the kidney. Because little is known about the receptors utilized by glomerular cells, we examined the attachment of cultured glomerular cells to extracellular matrix proteins. EXPERIMENTAL DESIGN: We produced monoclonal antibodies that inhibited the function of rat VLA-1 and VLA-2 and used these antibodies alone and in combination to explore the attachment of glomerular epithelial cells (GEC) and mesangial cells to extracellular matrix proteins in vitro. RESULTS: Cultured GEC utilize only VLA-2 for attachment to collagen but use it together with VLA-1 for adhesion to laminin. In contrast, mesangial cells use both receptors for their attachment to collagen but utilize only VLA-1 in their interaction with laminin. The use of VLA-1 by GEC and of VLA-2 by mesangial cells was unexpected because the expression of these receptors was barely detectable in an enzyme-linked immunosorbent assay and by immunocytochemistry. CONCLUSIONS: VLA-1, VLA-2, and VLA-3 are integrin receptors with overlapping specificities in that all have the potential to interact with collagen and laminin. Our studies demonstrate that cultured GEC use VLA-1 and VLA-2 almost exclusively for their adhesion to these ligands, and thus VLA-3 appears to play a negligible role in such attachment. Interestingly, GEC and mesangial cells differentially modulate the ligand binding specificities of VLA-1 and VLA-2. In situ, VLA-1 has been localized within the mesangium, whereas VLA-2 has not been detected within the glomerulus leading to the conclusion that GEC do not use VLA-1 or VLA-2 and that mesangial cells fail to utilize VLA-2. However, our studies have shown that, even when such receptors are barely detectable on the surface of cultured cells by sensitive techniques, they can play a functional role. These results suggest either that the levels of expression in situ are too low for the relatively insensitive immunohistochemical techniques employed, and thus the importance of these receptors to glomerular cell attachment in vivo is under appreciated or that such receptors are the result of de novo expression by glomerular cells when they are subjected to in vitro culture conditions. Because it is known that such conditions may mimic pathologic stress, we are presently examining the expression of these receptors by glomerular cells in various disease models.

Animals↗

Microvasculature of the pancreas, liver, and kidney in cerulein-induced pancreatitis.

Edematous pancreatitis was induced in 12 male Sprague-Dawley rats using supramaximal doses of the cholecystokinin analogue cerulein (5 micrograms/kg per hour). The microvasculature of the pancreas, liver, and kidney was examined using scanning electron microscopy of microvascular corrosion casts in 12 test animals and four controls at intervals of 30 minutes, 1 hour, 2 hours, and 4 hours. Distortion of the pancreatic and hepatic microvasculature was seen as early as 30 minutes and progressed during the study period. The renal vasculature remained normal throughout. Light microscopic analysis revealed no morphologic abnormalities in the walls of the pancreatic, hepatic, or renal microvasculature. This study demonstrates that cerulein-induced pancreatitis is associated with marked distortion of the pancreatic and hepatic microvasculature; the abnormalities start early in the disease and progress during the study period.

Animals↗

Temporal relationship of acinar and microvascular changes in caerulein-induced pancreatitis.

A study in rats investigated the temporal relationship between acinar cell changes and alterations in the local microvasculature in oedematous pancreatitis produced by administration of caerulein 5 micrograms kg-1 h-1. Samples were taken from experimental and control animals after 15 min, 30 min, 1 h and 2 h of caerulein infusion. Transmission electron microscopy showed ultrastructural acinar cell changes after 15 min whereas the earliest microvascular changes were seen after 30 min. Ultrastructural alterations in the acinar cells thus preceded local microvascular changes. Microvascular distortion appears to be a consequence and not a cause of pancreatitis in the caerulein model.

Animals↗