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Biomedical subjects

D D Davidson

Publications and source records attributed to D D Davidson.

At least 19 recordsLinked to original sources

Down-regulation of GATA-2 transcription during Pneumocystis carinii infection.

Differences in gene expression between Pneumocystis carinii-infected and noninfected rats were examined. Total RNA was isolated from homogenized rat lungs and then subjected to differential display with combinations of oligo(dT) and various arbitrary PCR primers. Approximately 50 differentially expressed bands were observed. Several of these DNA bands were isolated, reamplified, and cloned. The cloned DNA fragments were used as probes to perform Northern hybridization on RNA from P. carinii-infected and noninfected rat lungs. One clone was found to react with a 3-kb mRNA from noninfected but not from P. carinii-infected rat lung, suggesting that the gene represented by this clone was down-regulated during P. carinii infection. The nucleotide sequence of this clone was determined and found to be 97% homologous to the mouse GATA-2 transcription factor. In situ hybridization using RNA probes derived from this clone revealed that alveolar macrophages, resident lung monocytes, and bronchial epithelial cells express the GATA-2 gene in the lung.

Animals↗

Pulmonary emboli from pulse-spray and mechanical thrombolysis: evaluation with an animal dialysis-graft model.

PURPOSE: To compare pulmonary emboli resulting from pulse-spray pharmacomechanical thrombolysis (PSPMT) and mechanical thrombolysis performed to declot dialysis-access grafts. MATERIALS AND METHODS: Polytetrafluoroethylene arteriovenous shunts were created in eight dogs and were deliberately clotted at monthly intervals. Animals were randomly assigned to treatment with pulse-spray urokinase thrombolysis or a low-speed rotational percutaneous thrombolytic device. Perfusion imaging, pulmonary-artery pressure measurements, and pulmonary arteriography were performed before and after each procedure. RESULTS: A total of 22 procedures were performed (11 PSPMT and 11 mechanical thrombolysis). Declotting was successful in all procedures, with 100% 30-day patency. Segmental defects were seen on perfusion images after 10 (91%) of 11 PSPMT procedures and two (18%) of 11 mechanical thrombolysis procedures (P < .002). Transient increases in pulmonary-artery pressure occurred in the PSPMT group. Complete resolution of emboli and return to baseline pressures were seen in all cases, even after multiple (up to four) procedures in the same animal. There was no histologic evidence of pulmonary infarction in either group. CONCLUSION: The percutaneous thrombolytic device is effective for declotting dialysis grafts in dogs and results in statistically significantly fewer pulmonary emboli compared with PSPMT.

Animals↗

Study of thrombus from thrombosed hemodialysis access grafts.

PURPOSE: To determine the volume and composition of clot within thrombosed hemodialysis access grafts. MATERIALS AND METHODS: Clots were collected in 22 patients at surgical thrombectomy of polytetrafluoroethylene grafts. Histologic analysis was performed in 10 of these clots plus 21 randomly selected clots from the pathology archives. RESULTS: A small, firm piece of whitish thrombus ("arterial plug") was almost always recovered from the arterial limb of the graft. This plug had a concave surface and ranged from 5 mm to 3 cm in length. The remaining clot was soft, red thrombus. The mean weight of all clots was 3.4 g, and mean volume was 3.2 cm3. Average graft length was 42 cm. Histologically, the arterial plug had a characteristic appearance of densely compacted alternating layers of erythrocytes and fibrin. CONCLUSION: Clot volume in thrombosed dialysis grafts is much less (approximately equal to 25%) than would be expected if the graft were completely filled with thrombus, a finding of significance to mechanical thrombolytic techniques. Resistance of the arterial plug to pulse-spray thrombolysis is likely due to compaction.

Arm↗

Recent developments in hereditary nephritis (Alport's syndrome).

Hereditary nephritis with deafness, or Alport's syndrome, is a familial disorder characterized by progressive renal insufficiency, sensorineural hearing loss and ocular abnormalities. The Alport's nephropathy appears to result from a primary biochemical defect of the glomerular basement membrane, specifically an alteration of type IV collagen. The cardinal clinical manifestation of Alport's is chronic hematuria. End-stage renal disease develops in most affected males, while affected females generally experience a benign renal course. The diagnosis depends on characteristic electron microscopy findings of a variably thickened and thinned glomerular basement membrane with lamellation and basket weaving. Alport's is a genetically heterogeneous disorder with several modes of inheritance. A review of the literature with discussion of the clinical and basic science aspects of hereditary nephritis is presented.

Adolescent↗

Unusual presentations of lymphoma of the head and neck in childhood.

Lymphoma of the head and neck in children can pose a significant diagnostic problem, especially when histologic analysis indicates non-Hodgkin's lymphoma and the initial site of involvement is extranodal. This report describes 15 pediatric cases of lymphoma seen from 1981 to 1987 with an initial presentation in the head and neck. Cervical lymph nodes represented the initial site of involvement in 10 of the cases. The other five cases presented with disease in the tonsillar fossa; maxillary sinus and mandible; parotid; pharyngeal wall; trachea and thyroid gland; and ethmoid sinus, sphenoid sinus, and anterior fossa. The histologic type was non-Hodgkin's lymphoma in 12 cases and Hodgkin's lymphoma in 3 cases. Our experience has shown that lymphoma of the head and neck in children presents a confusing clinical picture and was initially confused with inflammatory disease, polymorphic reticulosis, and other neoplasms such as rhabdomyosarcoma. In one patient, Epstein-Barr virus infection and an inherited immunodeficiency state probably played a role in the pathogenesis of the lymphoma.

Adolescent↗

Epiphysiodesis by electrocautery in the rabbit and dog.

Numerous experiments have demonstrated arrest of longitudinal bone growth by traumatizing the epiphyseal growth plate. Recently, promising studies have been performed using less invasive means to produce epiphysiodesis than the conventional surgical technique. The distal femoral physeal plate was cauterized in 20 rabbits and 17 dogs through an inserted needle and a standard operating room electrocautery machine. The result showed a progressive distal femoral length reduction without angular deformities in the experimental limb averaging 3 mm at two weeks to 11.6 mm at 20 weeks after the surgical procedure in the rabbit and 11.5 mm at 12 weeks in the dog. Histologic sections demonstrated thermal injury to the physis followed by a progressive narrowing and eventual resorption of the growth plate.

Animals↗

High-frequency percussive ventilation compared with conventional mechanical ventilation.

In seven patients with severe respiratory distress, conventional mechanical ventilation and PEEP were used initially for respiratory support, which was changed to high-frequency percussive ventilation (HFPV) at the same level of airway pressure and FIO2. During both modes of ventilation, patients could breathe spontaneously via a low-threshold demand valve. With HFPV, PaO2 improved significantly (p less than .01) compared with PaO2 during conventional methods. Cardiac output was unaffected by the change to HFPV.

Carbon Dioxide↗

Suppression of murine immunologic functions by fresh and cultured human tumor extracts.

The role of human tumor-derived immunoregulatory factors (IRF) in the suppression of murine in vitro cell-mediated immune systems was investigated. IRF was extracted from a fresh human colon carcinoma and a liposarcoma using 3 M KCl. These extracts have previously been shown to suppress in vitro human immune responses. Both IRF extracts inhibited PHA-stimulated murine splenocyte [3H]Tdr uptake in a dose-dependent manner while extracts of normal tissue were not inhibitory. To further investigate in vitro immunosuppression a (C57BL/6 X A/J) F1 anti-B10. BR mixed lymphocyte reaction (MLR) was developed. Optimal [3H]Tdr incorporation was on Day 4 with 1 X 10(5) responders and 2 X 10(5) irradiated stimulators. Addition of IRF caused a 56% inhibition of this response but did not alter the kinetics of the MLR response. Induction of cell-mediated cytotoxicity (C57BL/6 X A/J F1 vs B10.D2) was significantly inhibited by addition of IRF during in vitro sensitization. Release of 51Cr from P-815 targets was decreased to spontaneous release levels at an effector:target (E:T) ratio of 20:1 when IRF was present during sensitization. At this E:T ratio, cells sensitized in the presence of a normal muscle 3 M KCl extract or medium caused 71 and 60% 51Cr release, respectively. IRF activity could also reproducibly be extracted from two small cell lung carcinoma tissue culture lines grown under a variety of culture conditions or passaged in nu/nu mice. The biochemical characteristics of the factor inhibiting human and murine lymphoid cell proliferation were identical. Thus, this system provides a convenient model for assessing the activity of human tumor-derived immunoregulatory factors.

Animals↗

Increasing phantom limb pain as a symptom of cancer recurrence.

Previous studies have shown that phantom limb pain following major amputation reaches its greatest severity 2 to 3 weeks following amputation; it then gradually diminishes over subsequent months and years. Transient episodes of severe phantom limb pain are sometimes temporally related to specific activities such as urination, sexual intercourse, or local pressure applied to the amputation stump. Also, neuroma formation may be associated with transient episodes of increased discomfort usually associated with the application of local pressure. Phantom limb pain progressively increasing over an extended period of time has not been previously reported. The authors observed phantom limb pain of increasing severity to be associated with locally recurrent extremity sarcoma in two patients. In both patients increasing phantom limb pain was the first indication of recurrent cancer and led to radiologic studies and biopsy which confirmed the diagnosis of recurrent disease. It is suggested that phantom limb pain of progressive increasing severity may be a symptom of locally recurrent cancer in an amputation stump.

Adult↗

Syngeneic humoral immune responses to tumor-associated antigens expressed by K-1735 UV-induced melanoma and its metastases.

An enzyme-linked immunoassay (ELISA) was developed to study syngeneic humoral immune response to a primary tumor and its metastases in the K-1735 ultraviolet light (UV)-induced C3H murine melanoma system. Binding of sera from syngeneic animals previously immunized with primary tumor or metastatic tumor tissue (M-3, M-4) to corresponding 3 M KCl extracts of tumor was significantly greater than binding of control C3H mouse serum. Antibody binding was not significantly reduced by competitive binding with syngeneic murine muscle or liver extracts, indicating the presence of tumor antigen(s) not shared by normal murine tissue. Antibodies to the tumor-associated antigens were selectively removed by competitive binding with syngeneic K-1735 tumor extracts but not by the unrelated 102 murine sarcoma from C57BL/6. However, EL-4 extracts (C57BL/6) did inhibit antibody binding to the primary and both metastases. Further competitive binding studies demonstrated the presence of a common antigen(s) present on the primary tumor and both metastases. We conclude that the K-1735 UV-induced melanoma primary tumor and its metastases express serologically detectable shared antigenic determinate.

Animals↗

Tumor stasis factor (TSF): a possible mechanism for the regulation of tumor cell proliferation.

A new class of factors that regulates tumor cell division in vitro can be isolated from fresh and cultured tumor cells by 3 M KCl extraction. Tumor stasis factors (TSF) inhibiting cultured tumor cell proliferation were extracted from 8 of 11 fresh human tumors and 2 cultured tumor cell lines. TSF inhibited [3H]Tdr incorporation by allogeneic and autologous cultured tumor cells in a dose-dependent manner. Extracts of normal human tissues and benign tumors did not demonstrate inhibition with the exception of liver. The mechanism of inhibition was cytostatic and not cytotoxic as demonstrated with trypan blue exclusion by tumor cells following TSF treatment, maintenance of intact tumor cell monolayers following addition of TSF, and lack of inhibition of Con A-mediated lymphocyte proliferation by TSF. TSF activity could be reversed by washing for up to 48 hr of incubation and was resistant to heat, pH alterations, reducing agents, proteases, and glycosidases. However, the active moiety bound to lentil lectin and could be purified 80-fold by preparative isoelectric focusing. These factors may represent a novel regulatory mechanism for tumor cell proliferation.

Cell Division↗

Surgical problems of diverticula of the small intestine.

During a 25 year period at this medical center and the UCLA Center for Health Science, we identified 34 patients who had jejunal or ileal pseudodiverticula. Seventeen of these were treated for a more significant pathologic condition, the diverticula being an incidental finding. Of the remaining 17 patients, six underwent an operation for complications of these diverticula; two of them had diverticulitis of the jejunum; two, a perforated ileal diverticulum, and two others, severe malabsorption. Another two patients had laboratory evidence of malabsorption attributed to the presence of the diverticula and were treated medically. In the remaining nine persons, four were diagnosed as having a functional bowel syndrome and five had undiagnosed abdominal pain. For the group of six patients undergoing an operation, there was a 50 per cent mortality. Our experience gives weight to the contention that, although jejunal and ileal diverticula are rare, in any collected experience with them, significant morbidity and mortality accompanies the complications.

Adult↗

The morbid anatomy of the skeleton in osteogenesis imperfecta.

Clinically, the two most prominent features of osteogenesis imperfecta are dwarfing and bone fragility. Radiologic examination reveals severe osteopenia with or without multiple deformities. Histological examination of samples obtained from 16 iliac crest biopsies compared with 21 age-matched controls revealed a significantly diminished amount of bone matrix without an associated decrease in the number of bone cells, suggesting a quantitative deficiency of collagen production. Radiologic studies of 46 affected children and autopsy studies of two children revealed abnormalities in the ossification of the secondary centers of ossification, together with evidence of fracture and fragmentation of the epiphyseal growth plates causing a characteristic radiologic appearance which may be likened to a bag of popcorn. These epiphyseal abnormalities may contribute to the limb shortening in some cases.

Bone and Bones↗

Abdominal and pelvic needle aspiration biopsies: can we perform them well when using small needles?

BACKGROUND: The aim of this study was to compare abdominal fine-needle aspirations (FNAs) performed with large (>/=20-gauge) or small (</=21-gauge) needles for diagnostic rate, number of samples required for diagnosis, diagnostic accuracy, and complication rates. METHODS: Abdominal and pelvic FNA procedures were retrospectively reviewed. Needle size, imaging guidance used, number of pathology slides created, complications, and cytologic and final diagnoses were obtained by reviewing radiologic, medical, and cytology records. RESULTS: Two hundred ninety procedures were included in the study. Two hundred fifty-seven were performed in patients having only one biopsy during the study interval. Of these, 159 had biopsies using small needles and 98 using large needles. Small needle biopsies had as high a diagnostic rate as did large needle biopsies (97.5% vs. 92. 9%, p = 0.11). Small and large needle biopsies showed high diagnostic accuracy (96.1 and 98.9%, respectively; p = 0.27). Incorrect cytologic diagnoses plus nondiagnostic examinations composed 6.3% of biopsies using small needles and 8.2% of biopsies using larger needles (p = 0.62). Complication rates were low. Average number of needle passes tended to be lower when small needles were used. CONCLUSION: Small needles can be successfully used for abdominal and pelvic FNAs. Small needles require the same or fewer needle passes, have low risk, have the same or improved ability to obtain diagnostic material, and achieve correct diagnoses compared with larger needles.

Abdomen↗