Somatostatin receptor-based imaging in malignant lymphomas.
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Hodgkin Disease↗
Biomedical subjects
J P O'Brien
Publications and source records attributed to J P O'Brien.
A phase I trial of intrahepatic verapamil and doxorubicin. Regional therapy to overcome multidrug resistance.
BACKGROUND: Verapamil can modulate multidrug resistance in vitro, but only at levels that are not tolerable when administered systemically. Regional strategies of drug administration may permit the delivery of high concentrations of a drug to specific areas with lower systemic levels. Colorectal cancers typically express the multidrug resistance phenotype. METHODS: A Phase I trial was performed to determine the maximum tolerable dose (MTD) and dose limiting toxicities of verapamil by hepatic artery infusion, together with doxorubicin, to patients with hepatic metastases of colorectal cancer. Fourteen patients with metastatic colorectal cancer received a 14-hour intrahepatic infusion of verapamil. Six hours after the start of the infusion, a fixed dose of doxorubicin (50 mg/m2) was given, also via the hepatic artery, over a 30-minute period. Patients were followed by cardiac telemetry but were not in an intensive care setting, and no invasive monitoring was used. All patients had received prior intrahepatic chemotherapy. RESULTS: The MTD of intrahepatic verapamil on this schedule in this patient population was 1.2 mg/kg/hour. Hypotension was the dose limiting toxicity. No major objective responses were noted in this heavily pretreated patient population. A dose of 1.0 mg/kg/hour is recommended for Phase II trials. CONCLUSIONS: Based on estimations of normal hepatic artery blood flow, the estimated concentration of verapamil delivered to the hepatic tumors at 1.0 mg/kg/hour is 3.6 micrograms/ml (7.3 microM), which is comparable to concentrations at which an in vitro reversal of MDR is seen. This study demonstrates that the systemic toxicities of an MDR reversal agent can be overcome by regional drug delivery, establishing this approach as an important model system for further study of MDR modulation.
Adenocarcinoma↗
Delayed pain response after lumbar discography.
The delayed onset of symptomatic pain following lumbar discography (with no immediate pain response) is described in six patients, five with a minimum 2-year follow-up. It is usually seen in patients with nearly normal disc morphology who have incomplete or discrete annular tears that are not filled at the time of injection. Later (2-12 h in this study), dye leakage occurs through these lesions, thereby precipitating the discogenic pain. This phenomenon may be missed and is probably more common than previously believed due to early discharge from the hospital, the patient expecting discomfort after the invasive study (hence no complaint is made), and the clinician being unaware of this delayed symptom, thereby not asking about it in follow-up. Close patient questioning regarding a delayed onset of symptomatic pain after discography is, therefore, an essential element in diagnostic information following this study.
Adult↗
Anterior lumbar fusion using a hybrid interbody graft. A preliminary radiographic report.
This is a radiographic report of 40 patients (20 men, 20 women) who underwent anterior lumbar interbody fusions (73 levels) utilizing a "hybrid" interbody graft composed of femoral cortical allograft (FCA) bone and iliac crest cancellous autograft bone. The average age at surgery was 38 years (range 17-64 years), and follow-up averaged 1.4 years (range 1.0-2.4 years). Nineteen of the patients had undergone previous lumbar surgery. Thirty-two patients (63 levels) underwent anterior fusion combined with some type of posterior fixation, and eight patients (10 levels) had no posterior fixation. Types of posterior fixation included: for 20 patients (36 levels) Steffee variable screw placement fixation, for 10 patients (23 levels) translaminar facet screws (TFS), for 1 patient (3 levels) Knodt rods and for 1 patient (1 level) facet screws. Based on the persistence of lucent lines at the graft-host interface, three patients (one level each) were felt to have non-unions at their latest follow-ups at 1.4, 1.5 and 2.0 years, respectively. Two of these patients had no posterior fixation, and the other had TFS fixation. The overall fusion rate was 96% (70 of 73 levels). The fusion rate for all levels treated with posterior fixation was 98% compared with 75% for those without fixation. Intervertebral disc heights (IVDH) were measured on all films and corrected for magnification with computer assistance. On average, the IVDH was increased postoperatively but returned to preoperative values at follow-up. IVDH loss was independent of the type of instrumentation used. No complications arose from the use of the hybrid graft.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder.
BACKGROUND: To determine the expression of P-glycoprotein in pre- and post-chemotherapy tumor tissue samples from patients with transitional cell carcinomas treated with M-VAC (methotrexate, vinblastine, adriamycin and cisplatin). PATIENTS AND METHODS: Fresh frozen tissue sections of primary and metastatic urothelial tumors were stained with mouse monoclonal antibody HYB-241 which recognized an external epitope of P-glycoprotein, using an avidin-biotin immunohistochemical technique. Immunoreactivity was scored separately in tumor cells and endothelial cells. RESULTS: Untreated primary lesions showed immunostaining in 6 of 46 cases (13%), while 6 of 16 (38%) post-therapy primary tumors were immunoreactive. None of the untreated metastases (0 of 17) were positive, however, 6 of 11 (55%) post-therapy specimens showed varied percentages of positivity for p-glycoprotein (p = 0.002). The highest percentage, 50%-70% of tumor cells stained, was observed in metastatic lesions from patients who had received 6 or more chemotherapy cycles. No difference in the proportion of endothelial cells stained was observed in pre- and post-therapy specimens. However, 3 of 6 post-therapy samples obtained from 5 individual patients showed MDR1 up-regulation on endothelial cells. CONCLUSIONS: The data show that an increase in the proportion of cells expressing P-glycoprotein occurs after exposure to a combination chemotherapy program containing drugs known to select for P-glycoprotein expression in vitro. The observation of increased immunoreactive endothelial cells suggests transactivation of the MDR1 in these cells. While data are preliminary, P-glycoprotein expression in capillary endothelial cells may contribute to drug resistance. Taken together, these mechanisms may contribute to therapeutic failure in patients with bladder tumors treated with chemotherapy.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A controlled hematoxylin-eosin for actinic elastosis-lysis. Its versatility and use for vascular damage (actinic arteriopathy) in the skin and orbit.
To demonstrate elastic tissue and its reactions in the skin and other organs, the hematoxylin-eosin staining method had been modified in two ways: (a) the hematoxylin solution is used once only to obtain its full potential, and (b) aqueous eosin is given greater selectivity by controlling its pH with a buffer. This stain highlights the broad supporting role of elastic tissue, particularly in pressure-containing blood vessels. It also helps to define the hyperplasia, degeneration, and elastolysis that arise from its peculiar sensitivity to actinic radiation.
Arteries↗
Anterior lumbar fusion options. Technique and graft materials.
The biomechanical requirements of the ideal lumbar interbody fusion are important in the surgical treatment of the vertebral endplates and graft selection. A series of 45 patients with anterior lumbar fusion were reviewed retrospectively. The fusion was performed with a composite construct consisting of femoral allograft cross-sections and allograft cancellous bone. Preparation of vertebral endplates consisted of scraping the endplate until punctate bleeding appeared. The major part of the endplate was preserved to withstand interspace distraction and stability. A 97% fusion rate was achieved based on flexion and extension analysis with a six- to 12-month follow-up period. A final average interspace distraction of 2.39 mm was reported. The graft should consist of a rigid structure that exceeds physiologic loads anticipated in the postoperative period, and the composition to promote arthrodesis. Anterior lumbar fusion with femoral allograft is an excellent procedure, but long-term further follow-up studies and statistical data are essential.
Biomechanical Phenomena↗
Reduction of severe lumbosacral spondylolisthesis. A report of 22 cases with a ten-year follow-up period.
Severe spondylolisthesis produces a kyphos at the lumbosacral junction. Reduction can be complicated by injury to the cauda equina. To prevent this, a posterior decompression and fusion is carried out before a slow reduction in extension. An anterior fusion with internal fixation then locks the reduction. Using these principles, a good reduction was achieved in 20 of 22 patients. Only two patients suffered a permanent neurologic deficit consisting of slight loss of ankle dorsiflexion. Severe spondylolisthesis can be safely reduced by this method.
Adolescent↗
Early failure of short-segment pedicle instrumentation for thoracolumbar fractures. A preliminary report.
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Humans↗
Observations of resorption of the posterior lateral bone graft in combined anterior and posterior lumbar fusion.
The past 10 years have seen the development of a surgical reconstructive procedure for the treatment of patients disabled with severe postlaminectomy syndrome. The technique involves anterior lumbar fusion, replacing the excised disc with bone graft, and under the same anesthetic, applying a posterolateral bone graft along with segmental instrumentation. The purpose of this report was to compare cases with fused and nonfused posterolateral grafts in cases where the anterior fusion was successful. Seventy-four interbody segments in 30 patients were fused while 47% (14 of 30) of the posterolateral bone grafts underwent resorption. Both allograft and autograft were used and this did not appear to influence the resorption seen at the 4-year follow-up period. The most likely factor to explain resorption of the posterolateral graft is deprivation of the proper mechanical forces in the lateral gutter by the simultaneous use of anterior lumbar interbody grafts.
Adult↗
Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.
PURPOSE: To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS: Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS: Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). CONCLUSION: Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.
Adolescent↗
Is damage by the sun and other actinic radiation the basis of temporal arteritis?
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Giant Cell Arteritis↗
Are we losing focus on the internal elastic lamina in giant cell arteritis?
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Animals↗
Comparison of technetium-99m-MIBI and thallium-201-chloride uptake in primary thyroid lymphoma.
A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2-methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl-chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma.
Female↗
Lysis of Neisseria gonorrhoeae initiated by binding of normal human IgM to a hexosamine-containing lipooligosaccharide epitope(s) is augmented by strain-specific, properdin-binding-dependent alternative complement pathway activation.
We studied the specificity of naturally acquired IgM bactericidal for strains of Neisseria gonorrhoeae that varied in sensitivity to the lytic action of normal human serum (NHS) and the relative ability of these strains to deplete the classical (CP) and alternative (ACP) C pathways. Lysis of both highly sensitive and relatively insensitive strains was inhibited by the same gonococcal lipooligosaccharides (LOS), as well as by Salmonella minnesota Re LOS and three hexosamine-containing glycose polymers. A polymer of N-acetylgalactosamine phosphate was the most inhibitory; a polymer of N-acetylglucosamine phosphate only partially inhibited. Neither 3-deoxy-D-manno-octulosonic acid (dOc1A) nor a polymer that contained dOc1A but not hexosamine inhibited NHS lysis. A co-polymer of N-acetylgalactosamine-dOc1A inhibited both bactericidal activity and the binding of IgM to the LOS of a highly serum-sensitive (sers) gonococcal strain. Carboxyl reduction of the dOc1A in this polymer did not affect its inhibitory capacity for gonococcal antibody, but abolished its binding to homologous antibody induced by vaccination. CP activity was not affected by vaccination. CP activity was not affected by absorption of NHS with gonococcal strains, whereas ablation of CP activity markedly but variously diminished lytic activity for highly sers strains. ACP activity was variously depleted by gonococcal strains, and the proportion of bacteria that could be lysed through the ACP varied among strains and among different populations of a given strain. The titer at which a strain was sensitive to NHS lysis was a function of its ACP consumption (p = 0.006), which accounted for 70% of the differences in titer among strains. Analyses of the absorbed sera revealed that the gonococci had variously depleted properdin from NHS as assessed by using an Ag-capture solid-phase RIA. Addition of purified properdin to absorbed sera restored ACP activity to normal levels. Western immunoblots of gonococcal lysates showed that purified properdin bound directly to a 39-kDa outer membrane protein. We conclude that both CP activation by IgM binding to LOS epitopes, one of which contains hexosamine, and ACP activation, which is a function of strain-specific direct binding of properdin, can initiate lysis of sers strains and that ACP activation, also enhances lysis and accounts for variations in sensitivity of sers strains.
Antigens, Bacterial↗
Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model.
Changes in nerve fiber numbers distal to a nerve repair in the sciatic nerve of 48 rats were evaluated over a 1- to 24-month period. The results of the morphometric evaluation in the sciatic nerve distal to the nerve repair demonstrated an increase in nerve fiber counts as early as 1 month following the nerve repair. The number of nerve fibers in the distal nerve was greatest at 3 months and did not return to normal levels until 24 months. The results of this study will influence the timing of experimental studies in which nerve fiber counts are critical for evaluation, and provides a better understanding of the clinical events occurring following nerve repair.
Animals↗
A study of elastic tissue and actinic radiation in "aging," temporal arteritis, polymyalgia rheumatica, and atherosclerosis. The actinic storm in the modern world.
Solar radiation provokes a lifelong series of destructive changes in the supporting elastic tissues of "exposed" skin. Called actinic elastosis/lysis (or actinic "aging"), the sequence begins in early life as simple elastic hyperplasia, converts in middle life to progressive actinic elastotic degeneration, and, in late life, typically ends with a stage of resorption (elastolysis) and atrophy ("aged" skin). Superficial "exposed" arteries such as the temporal artery participate in the same sequence of degenerative elastotic changes, which, as in the skin, may provoke granulomatous responses in a few of the many subjects affected. In the case of the temporal artery, a contingent outcome may be giant cell (temporal) arteritis and its recognized systemic vascular expression, polymyalgia rheumatica. Actinic commotion at the surface of the body is often massive in degree and extent and may be expected to exert a deleterious autoimmune impact on the essential elastic tissues of the arterial system. For this reason, solar radiation should be recognized as a risk factor for other elastic-related vascular diseases, including atherosclerosis and aneurysms. Man-made radiations may be exacerbating the effects of predominant solar radiation. Of the many radiant bands that make up the actinic (electromagnetic) spectrum, little is known for certain about the identity of those that cause these prevalent disorders of elastic tissue. Until this void is filled, more care should be taken with solar and the other "safe" radiations.
Arteriosclerosis↗