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Biomedical subjects

J C Watson

Publications and source records attributed to J C Watson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Importance of timing and length of administration of angiogenesis inhibitor TNP-470 in the treatment of K12/TRb colorectal hepatic metastases in BD-IX rats.

BACKGROUND: The timing and length of administration of angiogenesis inhibitor TNP-470 was altered to evaluate the effect on disease progression in a rat model of colorectal hepatic metastases. METHODS: Pair-fed BD-IX rats, injected intrasplenically with rat colon adenocarcinoma K12/TRb cells at day 0, were randomized to receive subcutaneous injections of either placebo or 15 mg/kg TNP-470 on alternate days: for 2 weeks beginning 24 hours after tumor inoculation ("Early"), for 4 weeks beginning 24 hours after tumor inoculation ("Prolonged"), or for 2 weeks beginning at day 15 after macroscopic tumor nodules were confirmed ("Delayed"). Response to treatment was evaluated by counting tumor nodules on the surface of the liver at laparotomy on day 14 and 28 after tumor inoculation. The animals were followed for survival and cause of death. RESULTS: Maximal suppression of hepatic metastases at day 28 required 4-week rather than 2-week TNP-470 administration. Prolonged TNP-470 administration resulted in significantly fewer hepatic metastases at day 28 compared to control (P < .05). Early and prolonged TNP-470 improved survival (Wilcoxon test, P < .05) compared with delayed TNP-470 and placebo. Delayed TNP-470 administration did not increase survival or significantly diminish the number of metastases at day 28 compared with placebo. CONCLUSIONS: These data suggest that prolonged adjuvant antiangiogenic therapy may suppress colorectal hepatic micrometastases.

Animals↗
PubMed1999

The surgical management of spinal dural vascular malformations.

Spinal dural arteriovenous fistulas (AVFs) are the most common spinal vascular malformation. The spinal dural AVF is a disease of adults, primarily men, that is a cause of subacute progressive lower extremity myelopathy. The challenge for the optimum management of these patients is in making an accurate, early diagnosis. Definitive surgical intervention by interruption of the intradural draining vein is the treatment of choice.

Arteriovenous Malformations↗
PubMed1998

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Adolescent↗
PubMed1998

Determination of the ischemic threshold for brain oxygen tension.

Measuring brain tissue oxygenation is now possible due to major advances in the technical development of Clark-electrodes and fiberoptic systems. However, to make this technique clinically useful for both nurses and medical staff, the ischemic threshold for brain tissue oxygen tension (brain pO2) must be determined. Three end points were used for determination of the critical brain pO2 value. 1) Infarct determination after permanent middle cerebral artery occlusion in a feline model. 2) Threshold analysis using the schemic threshold for cerebral blood flow (CBF) as a "gold standard" in severely head injury patients. 3) Outcome analysis in severely head injured patients. Brain pO2 dropped to 19 +/- 6 mm Hg and 23 +/- 6, 4 to 5 hours after MCA occlusion in the cat (n = 12). In severely head injured patients, a brain pO2 < or = 19 mm Hg was correlated with poor outcome (n = 24). The ischemic threshold for (r)CBF of 18 ml/100 g/min corresponded to a brain pO2 of 22 mm Hg, in the same patients. By using the above mentioned end points as a reference, we found the critical value for brain pO2 to be in between 19 and 23 mm Hg. Clearly, the difference between our threshold value and the lower critical brain pO2 level found by other groups using the Licox system, needs to be clarified in a comparison study before a uniform threshold for brain pO2 can be determined.

Animals↗
PubMed1998

Surgical management of local and regional recurrent head and neck squamous cell carcinoma.

During 1997 more than 40,000 Americans developed a squamous cancer of the upper aerodigestive tract. Surgery and radiation therapy may have been used alone or together, with reasonable prospects for curing them of disease. The majority of patients whose cancer cannot be controlled are confronted with local or regional recurrence. Such recurrences often occur in sites of the head and neck that are suited to early detection during an office examination. Hence, many are treatable with curative intent. This review addresses various surgical approaches to these difficult management problems.

Carcinoma, Squamous Cell↗
PubMed1998

The interruption of transmission of indigenous measles in the United States during 1993.

BACKGROUND: The United States has a goal to eliminate all indigenous cases of measles by the year 2000. Initial interruption of indigenous measles transmission would be expected during a period of very low measles incidence as occurred during late 1993. METHODS: Indigenous measles cases (i.e. cases acquired in the United States and not traceable to any imported case) from 1993 were investigated to determine their source of infection. The probability of sustained undetected measles transmission between isolated indigenous cases was estimated. RESULTS: Of the 312 measles cases reported for 1993, only 25 (8%) occurred after September 19. Of these only 4 cases (16%) could be classified as indigenous. The estimated probability that any of these 4 cases resulted from indigenous measles transmission in theirs or any adjoining counties was 0.05 or less. CONCLUSIONS: Interruption of indigenous measles transmission appears to have occurred for the first time throughout the United States in 1993. This event provides strong support for the current national strategy for measles elimination. However, complete elimination of indigenous measles will require maintaining high population immunity to prevent spread from imported cases and attaining global measles control to prevent the importation of measles.

Adolescent↗
PubMed1998

Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging.

OBJECT: Pituitary surgery has been reported to produce remission of Cushing's disease with preservation of pituitary function in only 60 to 70% of patients. The inability to identify an adenoma accounts for most failed sellar explorations. Most negative surgical explorations occur in patients in whom magnetic resonance (MR) imaging of the pituitary demonstrates normal findings, which happens in at least 35 to 45% of patients with Cushing's disease. METHODS: To examine the usefulness of intraoperative ultrasonography (IOUS) for identifying an adenoma in patients with no demonstrable tumor (negative findings) on pituitary MR imaging. we prospectively assessed the results of IOUS in 68 patients with a negative (59 patients) or equivocal (nine patients) MR image from a consecutive series of 107 patients with Cushing's disease (64%). We compared surgical findings and outcomes in these 68 patients with a group of 68 patients with Cushing's disease and negative findings on MR imaging in whom IOUS was not available. Intraoperative ultrasonography localized a tumor in 47 (69%) of 68 patients with negative findings on MR imaging. Surprisingly, the size of the adenomas that were detected with IOUS compared with the size of those not detected did not differ (6.8+/-3.4 mm compared with 6.1+/-2.8 mm [mean+/-standard deviation], respectively [p=0.51). In four patients, no adenoma was found at surgery or in the pathological specimen ("true negative"). In eight patients, nine abnormalities detected by IOUS that were suspected adenomas were negative on exploration ("false positive"). Thus, IOUS has a sensitivity of 73% and a positive predictive value of 84% for detecting pituitary adenomas in patients with Cushing's disease and negative findings on MR imaging. Compared with the 68 patients who did not undergo IOUS. remission after surgery was improved (61 patients [90%] compared with 57 patients [84%]), the number of tumors found on exploration was increased (61 tumors compared with 51 tumors, p=0.02), and the number of hemihypophysectomies was decreased (five compared with 15; p=0.02) with IOUS. When the groups were compared after excluding patients with prior pituitary surgery, tumors were found in 91% versus 72% (p=0.008), and remission occurred in 95% versus 87% of patients, respectively, in the groups that had or did not have IOUS. CONCLUSIONS: The IOUS is a sensitive imaging modality when used in patients with Cushing's disease in whom findings on pituitary MR imaging are negative. The improved ability to detect and localize these tumors by using IOUS positively affects surgical outcome.

Adenoma↗
PubMed1997

The rationale for, and effects of oxygen delivery enhancement to ischemic brain in a feline model of human stroke.

Reduced brain tissue oxygenation is frequently seen in severe head injury and after subarachnoid hemorrhage, and this is considered a major cause of secondary ischemic brain injury. In fact, in a previous study, we found a tight correlation between low brain tissue oxygen tension and poor outcome. Therefore, we tested the hypothesis that an allosteric modifier of hemoglobin, which improves oxygen transport to tissue, could reduce the size of an acute infarct in a feline model of human stroke. This compound produces a shift in the hemoglobin dissociation curve to the right and therefore facilitates the unloading of oxygen during low oxygen tension. Seventeen adult cats were studied. Ischemic stroke was induced through a transorbital, permanent, middle cerebral artery occlusion. Seven animals received saline, and 10 received the allosteric Hb modifier RSR-13. Three different endpoints were used to determine the effect of the allosteric modifier. Delta p50 values were measured in the arterial blood; the intra-infarct oxygen tension was measured, and finally, the volume of the infarct was assessed using TTC staining. Mean delta p50 changes varied from 10.4 +/- 9.2 mmHg up to 15.0 +/- 6.8 mmHg. Mean intra-infarct oxygen tension was 27 +/- 6 mmHg for the control group and 33 +/- 7 mmHg for the drug-treated animals. The mean infarct size (measured as percentage of hemisphere volume) in the control group was 32 +/- 9% and for the RSR-13 animals 22 +/- 10% (p < 0.05). A definitive trend towards improvement in brain oxygen tension was seen, such that animals pretreated with RSR-13 showed a higher infarct oxygen tension. Infarct size was significantly reduced in the drug group. Therefore, RSR-13 is potentially beneficial in the treatment of brain ischemia. Since human studies with this compound are already completed, and other compounds which increase oxygen delivery, such as perfluorocarbons, are already being evaluated, it is likely that oxygen delivery enhancement will rapidly become the first 'neuroprotective' modality, employed in patients with severe brain injury, stroke and subarachnoid hemorrhage.

Adult↗
PubMed1997

Breast cancer increases initiation of angiogenesis without accelerating neovessel growth rate.

BACKGROUND: Recurrence and mortality rates in patients with breast cancer correlate with the degree of tumor angiogenesis (angiogenic index). We have developed a novel angiogenesis model by using disks of fresh human placental vein that initiate an angiogenic response and exhibit linear radial capillary growth in culture. We hypothesized that the addition of human breast cancer cells to this human placental vein angiogenesis model would increase the incidence of angiogenesis and accelerate the rate of neovessel growth compared with vein disk cultured without tumor cells. METHODS: To test this hypothesis, vein explants from seven human placentas were incorporated into clots of 0.3% fibrin in Medium 199 and fetal bovine serum with or without 1.5 x 10(5) T-47D (n = 6 placentas) or MCF-7 (n = 1 placenta) breast cancer cells. Statistical differences between the experimental (with breast cancer cells) and control (no added cells) cultures were determined by repeated measures ANOVA. RESULTS: The proportion of disks exhibiting neovessel growth (initiation) by day 12 was significantly increased in the presence of T-47D cells (p < 0.05 at day 12, p < 0.001 at day 15). No statistical difference was seen in rates of neovessel growth (millimeters per day). Similar results were seen with MCF-7 cells. CONCLUSIONS: Tumor enhancement of angiogenesis may occur by increased initiation of the angiogenic response. Subsequent vessel growth rates may be tumor independent. We predict that effective antiangiogenic therapies will block a tumor's ability to augment angiogenesis initiation rather than subsequent neovessel growth.

Analysis of Variance↗
PubMed1997

Effects of the allosteric modification of hemoglobin on brain oxygen and infarct size in a feline model of stroke.

BACKGROUND AND PURPOSE: Cerebral ischemia and stroke are leading causes of morbidity and mortality. An approach to protecting the brain during ischemia is to try to increase the delivery of oxygen via the residual blood flow through and around ischemic tissue. To test this hypothesis, we used a novel oxygen delivery agent, RSR-13 (2-[4-[[(3,5-dimethylanilino)-carbonyl]-methyl]phenoxy]-2-methylpr opionic acid). Intravenous administration of RSR-13 increases oxygen delivery through allosteric modification of the hemoglobin molecule, resulting in a shift in the hemoglobin/oxygen dissociation curve in favour of oxygen delivery. METHODS: We studied RSR-13 in a feline model of permanent middle cerebral artery occlusion to assess its effects on cerebral oxygenation and infarct size. A randomized, blinded study of RSR-13 (n = 6) versus 0.45% saline (n = 12) was conducted, after an RSR-13 dose-escalation study (n = 4). Drug was administered as a preocclusion bolus followed by a continuous infusion for the duration of the experiment (5 hours). Brain oxygen was measured continuously with the use of a Clark oxygen electrode. Infarct size was measured at 5 hours after occlusion with computer-assisted volumetric analysis. RESULTS: The drug treatment group had consistently higher mean brain oxygen tension than controls (33 +/- 5 and 27 +/- 6 mm Hg, respectively) and significantly smaller infarcts (21 +/- 9% versus 33 +/- 9%, respectively, P < .008). We observed an inverse relationship between the dose response of RSR-13 (the shift in the hemoglobin/oxygen dissociation curve) and infarct size. CONCLUSIONS: These results are evidence that allosteric hemoglobin modification is protective to the brain after acute focal ischemia, providing a new opportunity for neuroprotection and raising the possibility of enhancing the protective effect of thrombolysis and ion channel blockade.

Aniline Compounds↗
PubMed1997

Hyperactive pectoralis reflex as an indicator of upper cervical spinal cord compression. Report of 15 cases.

Myelopathy from cervical spondylosis is often accompanied by hyperreflexia of the upper-extremity deep tendon reflexes (DTRs). Reflexes such as the pectoralis jerk and the deltoid jerk may only be apparent in the context of hyperreflexia. Although the nerve roots involved in the reflex arcs are well described, levels of cervical spinal cord compression that lead to the hyperreflexia are not as clear. This is of particular significance for patients with multilevel cervical spondylosis in determining the levels responsible for their symptoms. The authors examined 15 consecutive patients who presented for treatment of cervical myelopathy. The clinical examination was then correlated with levels of cervical spinal cord compression by cervical magnetic resonance imaging or computerized tomography with intrathecal contrast enhancement. The presence of a prominent pectoralis jerk was seen only in patients with spinal cord compression at the C2-3 and/or C3-4 levels (nine patients). No patient with compression at or below the C4-5 disc space without coexisting compression at a higher level had hyperactive pectoralis reflexes. This association between the C3-4 level and a hyperactive pectoralis reflex was significant (p < 0.004, Fisher's exact test). The deltoid reflex was tested in the last nine consecutive patients. It was present in patients with compression of the upper spinal cord at levels C3-4 and C4-5 (four of five patients) but appeared in only one of four patients with compression below C4-5. This association did not attain statistical significance. The presence of a hyperactive pectoralis reflex is specific for lesions of the upper cervical spinal cord. Examination of upper-extremity DTRs may be helpful in planning the appropriate levels for surgical decompression in patients with multilevel spondylosis and myelopathy.

Humans↗
PubMed1997

Intraoperative monitoring of substrate delivery during aneurysm and hematoma surgery: initial experience in 16 patients.

The effects of proximal occlusion of the parent artery during aneurysm surgery in humans are not fully understood, although this method is widely used. The reduction in substrate that can be tolerated by normal and subarachnoid hemorrhage (SAH)-affected brain is unknown. Therefore, the authors measured brain oxygen tension (brain PO2), carbon dioxide tension (brain PCO2), pH, and hemoglobin oxygen (HbO2) saturation before and after temporary occlusion in 12 patients with aneurysms. The effect of removal of a traumatic intracranial hematoma on cerebral oxygenation was also studied in four severely head injured patients. A multiparameter sensor was placed in the cortex of interest and locked by means of a specially designed skull bolt. The mean arterial blood pressure, inspired O2 fraction, and end-tidal PCO2 were analyzed. Brain PO2 and HbO2 saturation data were collected every 10 seconds. Descriptive and nonparametric analyses were used to analyze the data. A wide range in baseline PO2 was seen, although a decrease from baseline in brain PO2 was found in all patients. During temporary occlusion, brain PO2 in patients with unruptured aneurysm (seven patients) dropped significantly, from 60 +/- 31 to 27 +/- 17 mm Hg (p < 0.05). In the SAH group (five patients), the brain PO2 dropped from 106 +/- 74 to 87 +/- 73 mm Hg (not significant). Removal of intracranial hematomas in four severely head injured patients resulted in a significant increase in brain PO2, from 13 +/- 9 to 34 +/- 13 mm Hg (p < 0.05). The duration of safe temporary occlusion could not be determined from this group of patients, because none developed postoperative deterioration in their neurological status. However, the data indicate that this technique is useful to detect changes in substrate delivery during intraoperative maneuvers. This study also reemphasizes the need for emergency removal of intracranial hematomas to improve substrate delivery in severely head injured patients.

Adult↗
PubMed1996

In vitro activation of the interferon-induced, double-stranded RNA-dependent protein kinase PKR by RNA from the 3' untranslated regions of human alpha-tropomyosin.

The cellular kinase known as PKR (protein kinase RNA-activated) is induced by interferon and activated by RNA. PKR is known to have antiviral properties due to its role in translational control. Active PKR phosphorylates eukaryotic initiation factor 2 alpha and leads to inhibition of translation, including viral translation. PKR is also known to function as a tumor suppressor, presumably by limiting the rate of tumor-cell translation and growth. Recent research has shown that RNA from the 3' untranslated region (3'UTR) of human alpha-tropomyosin has tumor-suppressor properties in vivo [Rastinejad, F., Conboy, M. J., Rando, T. A. & Blau, H. M. (1993) Cell 75, 1107-1117]. Here we report that purified RNA from the 3'UTR of human alpha-tropomyosin can inhibit in vitro translation in a manner consistent with activation of PKR. Inhibition of translation by tropomyosin 3'UTR RNA was observed in a rabbit reticulocyte lysate system, which is known to contain endogenous PKR but was not seen in wheat germ lysate, which is not responsive to a known activator of PKR. A control RNA purified in the same manner as the 3'UTR RNA did not inhibit translation in either system. The inhibition of translation observed in reticulocyte lysates was prevented by the addition of adenovirus virus-associated RNA1 (VA RNAI), an inhibitor of PKR activation. Tropomyosin 3'UTR RNA was bound by immunoprecipitated PKR and activated the enzyme in an in vitro kinase assay. These data suggest that activation of PKR could be the mechanism by which tropomyosin 3'UTR RNA exerts its tumor-suppression activity in vivo.

Animals↗
PubMed1996

Phenylalanine ammonia-lyase gene structure, expression, and evolution in Nicotiana.

Phenylalanine ammonia-lyase (PAL) catalyzes the first reaction in the general phenylpropanoid pathway leading to the production of phenolic compounds with a significant range of biological function. A PAL gene we designated gPAL1, cloned from tobacco, consists of two exons separated by an intron of 1932 bp. Exon I, 398 bp, and exon II, 1747 bp, together encode a polypeptide of 715 amino acids. A putative TATA box and polyadenylation signal are found 144 bp upstream of the initiation codon and 193 bp downstream from the stop codon, respectively. Using various parts of gPAL1 as probes, genomic Southern blots indicated the presence of a small family of PAL genes in the tobacco genome that can be divided into two distinct subfamilies, one consisting of pal1 and pal2 and another of pal3 and pal4. Comparative genomic blot analysis of progenitor species (Nicotiana tomentosiformis and N. sylvestris) indicated that each species contains one PAL gene from each of the subfamilies, suggesting that pal1 and pal3 (or pal2 and pal4) diverged prior to the evolution of N. tabacum. Expression of the PAL gene family was examined using RNA gel blots. PAL transcript levels were significantly higher in flowers and roots than in leaves and stems of mature plants. PAL transcripts accumulate differentially during flower and leaf maturation in that mRNA levels decline during flower maturation but increase during leaf maturation. In leaves, PAL transcripts rapidly accumulated afer wounding.

Amino Acid Sequence↗
PubMed1996

The relationship between vivid description, emotional arousal, and in-session resolution of problematic reactions.

The relationships among clients' descriptions of external events, emotional arousal, and resolution of problematic reactions was examined. Clients (n = 12) explored problematic reactions with their therapists on 2 separate occasions. It was found that (a) resolution sessions, in contrast to nonresolution sessions, were characterized by high levels of referential activity (W. Bucci, 1985) when clients described problematic situations followed immediately by the differentiation of an emotional reaction by clients and (b) clients reported a change in mood immediately after the vivid descriptions of problematic situations. The findings highlight the role that vivid description can play in promoting clients' emotional arousal during the session and provide preliminary evidence for the validity of the performance model (L. N. Rice & E. P. Saperia, 1984).

Adult↗
PubMed1996

Measles vaccine effectiveness and duration of vaccine-induced immunity in the absence of boosting from exposure to measles virus.

BACKGROUND: It is unknown whether vaccine-induced immunity is lifelong in the absence of periodic exposure to measles virus. After 27 years of no known exposure to measles, an outbreak in Palau in 1993 offered the opportunity to study this issue and the measles vaccine effectiveness. METHODS: Household contacts of a sample of confirmed cases were interviewed for exposure, symptoms and vaccination status verified by records. Serum from symptomatic contacts was tested for measles antibodies. RESULTS: Among 78 contacts 4 of 5 (80%) unvaccinated, 4 of 35 (11%) 1-dose vaccine recipients and none of 38 (0%) > 1-dose recipients developed measles. Effectiveness of 1-dose vaccine was 86% (95% confidence interval, 60 to 95%). An additional dose significantly reduced the risk of measles (P = 0.048). Time since vaccination was not a significant risk factor for developing measles (relative risk, 1.6; 95% confidence interval, 0.3 to 9.4; persons vaccinated > 15 years ago vs. < 5 years ago). CONCLUSIONS: Similar to the estimates previously obtained in the area, measles vaccine effectiveness in Palau was lower than the estimates obtained in the US. A second dose of vaccine further reduced the risk for developing measles. We found no evidence that waning immunity was an important problem in this limited population with no known previous exposure to measles virus. The small number of vaccinated contacts precludes a definitive assessment.

Child↗