Biomedical subjects
Publications and source records attributed to D Mintz.
We describe the morphologic and signal changes detected about the proximal femoral growth plate in two patients with hip pain preceding the progression to slipped capital femoral epiphysis using magnetic resonance imaging.
BACKGROUND: Different viewing conditions (two- and three-dimensional National Television Standard Committee [2D-NTSC and 3D-NTSC] and two-dimensional high-definition television [2D-HDTV]) on telemanipulator performance were evaluated. METHODS: Six taskes were performed by 15 endoscopic surgeons using the daVinci telemanipulation system. Performance time and errors were measured. Encoder data from the system were used for kinematic analysis of motion. A self-evaluation questionnaire regarding performance under various viewing conditions was obtained. RESULTS: Resolution was better with 2D-HDTV. The estimate of relative distance was not influenced by the different visualization systems. Motor skill tasks were performed faster with binocular vision (3D-NTSC) than with monocular vision (2D-NTSC, 2D-HDTV). For both 2D settings, the deceleration phase of motion was prolonged (p < 0.05 vs 3D). Peak velocity was reduced with 2D-HDTV as compared with 3D-NTSC (p = 0.01). The surgeons tended to favor the 3D system despite their use of 2D systems in their own practice. CONCLUSIONS: Three-dimensional vision enhances telemanipulator performance as compared with a 2D system at the same or higher level of resolution. Because it allows faster and more precise movement, future surgical systems should focus on 3D visualization.
Sildenafil (Viagra), by virtue of its conflict-laden symbolic meanings, may be particularly likely to have psychosocial consequences, either therapeutic or disruptive. The author presents two cases of men in their mid-seventies who took sildenafil and who were admitted to a locked geropsychiatry unit because of homicidal ideation toward their wives that occurred while they were not under the direct effect of the drug. In one case, a wife's rejection of her husband's advances seemed to uncover many hidden resentments that they bore toward each other. In the other, sildenafil failed to restore potency to a patient with diabetes, and he developed a jealous delusion that his wife was having an affair.
Endotoxin (lipopolysaccharide; LPS) activates a wide variety of host defense mechanisms. In mammals LPS binding protein (LBP) and CD14 interact with LPS to mediate cellular activation. Using sucrose density gradients and a fluorescent endotoxin derivative we have investigated the mechanism of LPS binding to LBP and the soluble form of CD14 (sCD14). LPS binds to LBP to form two types of complex; at low ratios of LPS to LBP complexes with one molecule of LBP and 1-2 molecules of LPS predominate, while at high ratios of LPS to LBP a large aggregate of LBP and LPS predominates. Complexes of LPS with sCD14 do not form large aggregates, consisting of only 1-2 LPS bound to a single sCD14 even at high multiples of LPS to sCD14. LBP catalyzes LPS binding to sCD14. Catalysis by LBP apparently occurs because LBP provides a pathway for LPS to bind to sCD14 which avoids the necessity for LPS monomers in aqueous solution. The dissociation constants for LPS.LBP and LPS.sCD14 complexes were determined to be 3.5 x 10(-9) and 29 x 10(-9) M, respectively. These numbers suggest that when LBP and sCD14 are present at roughly equal concentrations as they are in normal human plasma and compete for limited LPS, the LPS will predominantly associate with LBP.
Only recently has the mechanism for lipopolysaccharide (LPS) recognition by macrophages been elucidated. In contrast to many ligand receptor interactions, the interaction of LPS with its receptor, CD14, on myeloid cells is greatly enhanced by prior complexation of LPS with LPS-binding protein (LBP), a recently discovered plasma glycoprotein. LBP is found in normal serum or plasma in the 5 to 10 micrograms/ml range. In plasma, it reacts rapidly but transiently with LPS. LPS-LBP complexes then react with CD14 bearing cells. Blocking CD14 with monoclonal antibodies or removal of LBP from plasma blocks the ability of the cells to react with LPS-LBP complexes and also blocks release of cytokines and other mediators from the cells. In the normal lung, bronchoalveolar lavage fluid contains low levels of LBP. However, during acute lung injury, LBP levels may rise by transudation and enhance activation of alveolar macrophages to release injurious mediators. Description of this pathway for LPS recognition by macrophages and other leukocytes offers the possibility of developing new reagents to block LPS recognition and prevent the development of endotoxemia.
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The BB rat is the experimental analogue of human juvenile diabetes mellitus. From 30 through 120 days after birth, 59 BB rats were treated with water (n = 20), or FK 506 in daily intragastric doses of 1 mg/kg (n = 19) or 2 mg/kg (n = 20). Diabetes developed in 75%, 15%, and 0% of the three groups. Animals protected from diabetes by FK 506, and killed in the nondiabetic state at 120 days had normal intraperitoneal glucose tolerance tests, virtual absence histopathologically of autoimmune insulitis, normal pancreatic insulin content, and immunocytochemical confirmation of islet insulin and glucagon content. Forty five to 75 days after stopping FK 506, about 3/4 of the animals who were diabetes free at 120 days have remained so. These results provide support for a clinical trial of FK 506 for recent onset diabetes.
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Port wine stains represent a relatively common congenital vascular lesion, often appearing on the head and neck. Sixty-six consecutive treatments of port wine stains are evaluated in this study. This represents 38 patients, with many of these patients receiving multiple treatments to different areas of the lesion. All patients were treated with a CO2 surgical laser system. Of these patients, 62.9% showed good to excellent blanching, with the remainder showing fair or poor results. Hypertrophic scarring occurred in 7.4% of cases. The CO2 laser represents another tool with which these lesions can be treated. Further clinical experience is required with both the argon and the CO2 laser if the treatment of these disfiguring lesions is to be improved.
Peripheral hyperinsulinemia may be associated with metabolic consequences that could contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. Arterial wall and striated muscle cells were studied in dogs to examine the effect of hyperinsulinemia on the lipid content and on lipogenic and glycolytic enzyme activity. Eight pancreatectomized dogs received segmental pancreatic autografts with venous drainage into the iliac vein. Glucose disappearance rates (K values) were normal four years after transplantation, but both fasting serum insulin levels (48.9 +/- 4.8 v 11.8 +/- 1.9 microU/mL) and the total area under the glucose-insulin response curve (1797 +/- 196 v 1110 +/- 158 microU X min/mL) were significantly greater than in control animals (P less than 0.05). The hyperinsulinemic dogs had a marked triglyceride elevation in arterial smooth muscle (20.6 +/- 8.0 v 0.5 +/- 0.4 mumol/g) and striated muscle (171.4 +/- 46.6 v 41.2 +/- 7.7 mumol/g) (P less than 0.001). Moreover, key enzymes in lipid synthesis (glucose-6-phosphate dehydrogenase, malic enzyme, and 3-hydroxyacyl-CoA DH) were significantly increased (P less than 0.01) in the hyperinsulinemic animals, while the glycolytic enzymes, (phosphofructokinase, hexokinase, pyruvate kinase, and alpha-glycerophosphate DH) were not significantly different. These data demonstrate substantial enhancement of lipid synthesis in arterial wall and striated muscle in hyperinsulinemic dogs. Altered substrate metabolism in arterial walls, in association with hyperinsulinemia, may have important implications with regard to macrovascular disease in diabetes, particularly in insulin-treated patients. In addition, these studies may serve to stimulate longer term assessments of macroangiopathy in the increasing number of patients with functioning pancreatic allografts draining into the systemic circulation.
From 1976 to 1983, 13 living related and 54 cadaver renal transplants were done in 62 patients more than 50 years old. Patients with no coronary or myocardial disease upon coronary angiography were selected preferentially for transplantation. Over-all 1-year patient and graft survival rates were 88 and 70 per cent, respectively. Among cadaver recipients graft survival was improved (p less than 0.001) when prophylactic antilymphoblast globulin was used. There were fewer steroid-related complications (p less than 0.001) in recipients managed with a low dose rather than a high dose maintenance prednisone regimen. With careful patient selection and a steroid-sparing immunosuppressive regimen, renal transplantation can be done safely in older recipients with no increased risk of death or graft loss.
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Prolonged survival of the vascularized free-draining intraperitoneal pancreatic segmental allografts (FDPS) has been observed previously in immunosuppressed beagle littermates matched for low mixed lymphocyte culture (MLC) reactivity. When rejection (hyperglycemia) did occur, it was abrupt, unpredictable, and irreversible. This contrasts with renal allograft rejection in which elevations of serum creatinine are reversible with increased immunosuppression. In the present experiments, low MLC-reactive littermate pairs underwent simultaneous transplantation of kidney and FDPS allografts from the same donor. Increases in serum creatinine from 0.5 mg/dl to 1.5 mg/dl (renal rejection) occurred 4 to 5 days after transplantation (mean = 20.5 +/- 4.1) and preceded the onset of hyperglycemia by 6 to 22 days (mean = 1.06 +/- 4.6) in nonimmunosuppressed animals. At the onset of kidney rejection but before hyperglycemia developed, renal allograft biopsies revealed generalized mononuclear infiltration, while FDPS biopsies showed diffuse interstitial infiltration, but islets of Langerhans appeared to be spared. Treatment intervention with azathioprine and corticosteroids at the time of creatinine elevation prevented the onset of hyperglycemia from 46 to greater than 260 days in four of nine animals. Biopsies after 2 weeks of therapy showed resolution of the lymphoid infiltrates in the kidney and limitation of infiltrates to perivascular areas in the FDPS allografts. Immunological monitoring of peripheral blood lymphocyte function demonstrated the development of positive in vitro cell-mediated lymphocytoxicity shortly before the onset of hyperglycemia but only after creatinine elevation was well established and biopsies revealed evidence of rejection in both the renal and FDPS allografts.
The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors. Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated lymphocytotoxicity (CML) assays revealed increases in CML before graft rejection in low MLC reactors, and decreases in both CML and MLC responses before graft rejection in high MLC reactors. FDPS graft survival was indefinite (>6 mo) in group II dogs, despite low-grade MLC reactivity (2:4 dogs) and CML responses (4:4 dogs). Biopsies of FDPS grafts at 6 mo in normoglycemic dogs showed disappearance of exocrine tissue and coalescence of islets in both groups I and II, but with less fibrosis in group I (immunosuppressed). These results indicate that (a) pancreatic islets in vascularized grafts (FDPS) may survive indefinitely in the presence of a good tissue match best predicted by MLC testing, (b) tissue specific histocompatibility factors appear to be common enough between kidney and pancreas to allow for long-term survival of both organs transplanted from the same donor, at least in appropriate recipients (group II), and (c) immunosuppression is associated with less fibrosis in FDPS allografts.
Because successful allotransplantation of islets of Langerhans isolated by collagenase digestion has been difficult in many animal species, we asked whether isolated islet preparations might have tissue specific determinants conferring amplified immunogenicity in vitro. Lymphocyte proliferative responses ([(3)H]thymidine uptake) were studied in beagle dogs in mixed culture combinations of lymphocyte vs. lymphocyte (MLC) and lymphocyte vs. islet (MLIC). In five MLC responder and five nonresponder pairs, peripheral blood lymphocytes of dogs A and B were used as responding cells, and dog B x-irradiated lymphocytes (Bx), x-irradiated (or nonirradiated) islets (BI), or hepatic cells (BH) were used as stimulating cells in primary and secondary reactions. For the secondary reactions, A + Bx, A + BI, or B + BI were incubated for 9 d (A'B, A'BI, B'BI, respectively) before addition of new stimulating cells. The results showed that islets were autostimulatory, eliciting a tissue-specific lymphoproliferative response in a primary MLIC. Thus, B + BI reactivity was evident at 3,5, and 7 d in primary culture, whereas collagenase-digested liver cells, or lymphocytes obtained from collagenase-digested lymph nodes did not stimulate autologous lymphocytes. A separate reactivity was observed in the allogeneic A + BI combination in MLC responder pairs, and the peak response of A + BI at 9 d was markedly greater than that of B + BI, suggesting the presence of major histocompatibility complex lymphocyte-defined locus determinants in the islet preparations, in addition to islet-specific determinants. A secondary reaction was observed if lymphocytes were primed with islets and challenged with islets (A'BI + BI or B'BI + BI), but not if they were challenged with lymphocytes (A'BI + Bx, B'BI + Bx) or hepatic cells (A'BI + BH, B'BI + AH). Furthermore, priming of lymphocytes with autologous islets (B'BI) led to exclusion of any reactivity against allogeneic lymphocytes, i.e., B'BI suppressed A + Bx, and B'BI also markedly suppressed phytohemagglutinin-stimulated lymphoproliferative responses. Experiments were performed that excluded the possibility that the insulin levels present in the MLIC, the presence of passenger lymphocytes in the islets, or the maintenance of islets in tissue culture for 1-7 d affected the observations. These results provide evidence for the existence of alloantigens as well as tissue-specific antigens on collagenase-isolated islets of Langerhans.
The authors' experience in dealing with 10 cases of chemodectomas occurring in head and neck is outlined. The symptomatology of these tumors is discussed with their investigation and management. Analysis of this series suggests that polytomography is the most valuable tool in diagnosing lesions within the confines of the temporal bone, whereas angiography is the most rewarding method of investigating cervical lesions. Surgical resection is the preferred method of treatment, and the most definitive. However, in those cases where the patient's general medical condition or the size and location of the tumor create unacceptable risk factors, radiotherapy may be employed as a palliative measure.