Biomedical subjects
Publications and source records attributed to J Jones.
Patients with advanced head and neck cancer continue to present a difficult management problem for the otolaryngologist-head and neck surgeon. This paper discusses the principles of radiation therapy with emphasis on neutron beam therapy as an effective treatment option for advanced malignancy of the head and neck other than squamous cell carcinoma.
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Sudden death secondary to acute dissection of a coronary artery is a rare, but increasingly recognized, cause of sudden, unexpected death in apparently healthy persons. It has been reported more frequently in women and has been associated with sudden death during the puerperium. It has also been reported that these involved coronary vessels contain increased numbers of eosinophils and often show areas of cystic medial necrosis. In this article, we report a case of sudden death in a 47-year-old white woman due to dissection of the distal segment of her left anterior descending coronary artery. There was marked involvement of the coronary arterial walls with cystic degeneration of the media with accumulation of glycosaminoglycans as demonstrated by Alcian blue staining. There was no eosinophilic infiltrate within the arterial walls. This case is unusual in that this woman's mother and brother both have had aneurysms, which stresses the importance of not only searching carefully for these lesions, but also of obtaining family history in such cases.
The petunia rbcS gene SSU301 was introduced into tobacco using Agrobacterium tumefaciens-mediated transformation. The time at which rbcS expression was maximal after transfer of the tobacco plants to the greenhouse was determined. The expression level of the SSU301 gene varied up to 9 fold between individual tobacco plants which had been standardized physiologically as much as possible. The presence of adjacent pUC plasmid sequences did not affect the expression of the SSU301 gene. In an attempt to reduce the between-transformant variability in expression, the SSU301 gene was introduced into tobacco surrounded by 10kb of 5' and 13 kb of 3' DNA sequences which normally flank SSU301 in petunia. The longer flanking regions did not reduce the between-transformant variability of SSU301 gene expression.
We have performed a serial-section electron microscopic study of the inner plexiform layer (IPL) of the retina of the turtle Pseudemys scripta elegans. A qualitative and quantitative assessment of the neuropil of the IPL has been done from photomontages taken from the linear visual streak area and peripheral retina. Counts of conventional, ribbon, serial, and reciprocal synapses, of ganglion cell dendrites, and of profiles containing large, dense-cored vesicles were made in five equal-thickness strata in each montage. Averages of these different features were plotted for each stratum in the linear visual streak and compared with peripheral retina. The trend was for stratum 2 to have the highest overall absolute number of amacrine and bipolar interactions, and also of serial synapses, both in the linear visual streak and in peripheral regions. Stratum 4 tended to have the second-highest number of synapses. The total number of synapses for the entire thickness of the IPL, regardless of stratification, is higher in the streak than in the periphery. The total amacrine-to-bipolar-synapse ratio in the IPL is the highest of any vertebrate studied to date (11.0 in the streak and 14.5 in the periphery) but the number of synapses/micron 2 was found to be similar to that reported for other vertebrates. Amacrine-to-amacrine synaptic contacts greatly outnumber other types of synapses; amacrines constitute the principal input to ganglion cells, whereas bipolar output is mainly onto amacrines. The trend for higher numbers of synaptic interactions in strata 2 and 4 of the streak region of the turtle IPL can be correlated with the branching of small-field amacrine and ganglion cells described in Golgi studies (Kolb: Philos. Trans. R. Soc. Lond. B 298:355-393, '82). In peripheral retina, branching of large-field amacrines and a lower number of bipolar pathways may account for the trend for larger numbers of amacrine synapses in strata 2 and 4. Profiles having large, dense-cored vesicles tend to occur most frequently in strata 1 and 5, which correlates well with the stratification in the IPL of the processes of immunoreactive amacrine cells described in other studies.
Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P less than .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving post-operative radiation (4,600-4,700 rad in 26-27 fractions; 5,100-5,300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P = .7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival.
Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.
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The objective of this study was to determine the responsiveness of isolated embryonic murine and avian epithelial and mesenchymal tissue to PGE2 stimulation. On days 12 and 14 of gestation, murine palatal epithelium responded to PGE2 (10(-5) M) with 3.5 and 4.0 fold elevations in intracellular cAMP, respectively. On day 13 of gestation, murine palatal epithelium was responsive to forskolin, PGE1 and isoproterenol as indicated by the accumulation of cAMP, but unresponsive to PGE2 and PGF2 alpha less than treatment. Avian palatal epithelium and mesenchyme, developmental stages 31 to 34, as well as murine palatal mesenchyme on day 13 of gestation responded to PGE2 treatment with dose-dependent elevations in intracellular cAMP. Of importance, is the lack of responsiveness of murine palatal epithelium to PGE2 treatment on day 13 of gestation. This corresponds to the time of murine palatal medial edge epithelial differentiation. Lack of a PGE2 response may effect, initiate or occur as the result of murine medial edge epithelial differentiation.
This is the first report of orbital involvement in systemic adult T-cell leukemia/lymphoma (ATLL). The etiologic agent of ATLL is the human T-cell leukemia virus-I (HTLV-I), the first retrovirus demonstrated to induce cancer in humans. The diagnosis of ATLL is based on characteristic clinicopathologic features in combination with serologic or virologic evidence of HTLV-I infection. Serum antibodies to HTLV-I were identified by immunofluorescent microscopy. Viral particles characteristic of HTLV-I were found in a culture of the patient's peripheral blood lymphocytes. The patient was a native of the Caribbean, one of the known endemic foci of HTLV-I infection. Adult T-cell leukemia/lymphoma should be considered in the differential diagnosis of orbital T-cell lymphomas.
Continuous measurement of arterial oxygen saturation (SaO2) using pulse oximetry has become a common monitoring and management technique in critically ill hospitalized patients. To determine the impact of SaO2 monitoring on emergency patient management, we conducted a prospective uncontrolled clinical trial on 40 adult patients presenting to the emergency department with acute respiratory illness, such as emphysema, asthma, or pulmonary edema. Recorded data included hemograms, arterial blood gases, subsequent therapy, and response to treatment. Additionally, the "early warning" capability of SaO2 monitoring was analyzed by recording the severity and outcome of hypoxemic events during treatment. Mean duration of usage for the 40 oximeters in the ED was 1.8 hours; all probes functioned reliably over a wide range of systolic pressures (80 to 206 mm Hg), heart rates (40 to 180 beats per minute), and hematocrits (20% to 58%). There was good correlation between simultaneous pulse oximeter values and both directly measured SaO2 (r = 0.95) and saturations derived from measured arterial PaO2 (r = 0.94). The device detected several otherwise unrecognized drops in arterial saturation that were confirmed by laboratory analysis. Other clinical situations in which the pulse oximeter was found useful in the ED are reviewed. We conclude that continuous measurement of SaO2 can improve the monitoring of ED patients, increase the precision of therapy, detect hypoxemia during intubation, suctioning, and other treatments, and detect clinically unsuspected changes in arterial oxygenation.
As the number of elderly persons in the United States continues to increase, geriatric abuse has become the most recent manifestation of domestic violence seen in the emergency department. Recent data suggest that 1 million elderly persons are battered, neglected, or exploited each year by family members or caretakers. This maltreatment may be more difficult to identify than child or spouse abuse because of the relative isolation of the victims and their reluctance to report abuse. Many of these cases involve only subtle signs and have a great potential to pass undetected. We summarize the current literature on geriatric abuse and describe an ED protocol for identifying and reporting suspected victims. We retrospectively reviewed the medical records of 36 elderly patients hospitalized with documented abuse or neglect. Physical maltreatment was evident in 29 patients (80%), and 16 of the cases (44%) involved psychological abuse. Key points in the history, physical examination, and psychosocial evaluation were analyzed to identify specific criteria used in the development of the protocol. This framework will aid the emergency physician in the crucial first steps of identifying abuse, obtaining evidence, and providing immediate treatment and crisis intervention. Awareness that the problem exists and improved detection and intervention procedures are needed to prevent abuse of elderly persons from becoming more widespread.
Because the presentation and clinical features of infectious mononucleosis can be misleading in the elderly, a significant number of infections may go unrecognized. We report an unusual case of infectious mononucleosis in a 61-year-old man in whom marked visual impairment was the presenting complaint and severe optic neuritis was the only prominent finding. Confirmation of the diagnosis was made by serologic testing for Epstein-Barr virus antibody. Recovery of visual function was near complete, but optic atrophy persisted. We reviewed the English literature and collected seven cases of well-documented optic neuritis associated with infectious mononucleosis. A clinical profile of parainfectious optic neuritis is discussed along with the likely pathogenesis for this complication.
The relationship between the endogenous cytoplasmic levels of the enzymes superoxide dismutase and catalase and the inhibition of cell proliferation by radiation has been studied in 11 mouse cell lines. The resistance of these mouse cell lines to radiation was found to vary by over 25-fold. No correlation was found between the cytoplasmic level of CuZn-superoxide dismutase or catalase and the resistance to radiation as measured by extrapolation number (EN), quasi-threshold dose (Dq), or DO. None of the cell lines had detectable cytoplasmic Mn-superoxide dismutase. The apparent Ki of potassium cyanide for mouse CuZn-superoxide dismutase was determined (Ki = 6.5 mumol dm-3).
Benzamides are potent inhibitors of nuclear ADP-ribosyltransferase and have been extensively used to demonstrate the involvement of ADP-ribosylation in cellular function. When permeabilized L1210 cells are treated with 50 microM 3-acetylamidobenzamide (3-aab) the enzyme is inhibited. However, when 50 nM 3-aab is used a two-fold stimulation of enzyme activity is produced. This anomalous stimulation is obtained with benzamides and nicotinamides and is correlated with their activity as inhibitors. Strikingly the steady-state level of poly(ADP-ribose) in intact cells is increased by these low levels of inhibitors. The mechanisms of this effect and its consequences for the experimental use of benzamides are discussed.
This study was designed to investigate a postulated relationship between vitamin B-12 and leucine metabolism in mature domestic chickens. Plasma amino acid analysis revealed the presence of beta-leucine at a concentration of 60 to 80 mumol/l. After 425 d on a vitamin B-12-deficient diet, plasma beta-leucine was 133% higher (P less than 0.06) and plasma leucine and methionine lower (P less than 0.03) than values in plasma from hens fed a diet adequate in vitamin B-12. Branched-chain-amino-acid aminotransferase (EC 2.6.1.42) (BCAT) activity was not enhanced by vitamin B-12 deprivation (P greater than 0.05). In contrast to leucine, beta-leucine was not utilized as substrate by BCAT for the formation of alpha-ketoisocaproate. Kidney extracts possessed leucine 2,3-aminomutase (EC 5.4.3.7) (LAM) activity, as evidenced by enhanced conversion of beta-leucine to alpha-leucine in the presence of adenosylcobalamin. LAM activity could not be demonstrated in liver or muscle extract, while leucine formation by pancreas extract was negligible. These data represent the first evidence of the presence of the amino acid beta-leucine in chicken plasma. In addition, the data support vitamin B-12-dependent leucine synthesis from beta-leucine in the chicken and highlight the kidney's role in leucine synthesis.
Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least two samples of clear follicular fluid (FF) collected in the late follicular phase. The cohort concentrations of Insulin-like Growth Factor-1 (IGF1) were significantly correlated with serum IGF1 and dominant follicles contained significantly higher concentrations of IGF1 and oestradiol (E2) than their cohorts. After the LH surge, a further significant increase in dominant FF-IGF1 occurred. FF-(log)E2 was significantly correlated with both FF-IGF1 and FF volume. Nine women with the polycystic ovary syndrome (PCOS) and one patient with multicystic ovaries (MCO) associated with weight-loss related amenorrhoea also had follicular aspiration performed. The mean (SD) FF-IGF1 in the PCOS group, 0.42 (0.15) U/ml, was not significantly different from that of the cohorts in the control group, 0.39 (0.13) U/ml. The patient with MCO had both serum and FF-IGF1 concentrations less than 10th centile. These results support the hypothesis that IGF1 has a paracrine (and possibly endocrine) role in the regulation of ovarian function in the human female.
We have studied eight children with primary hypothyroidism (6F, 2M) aged 6.7 to 14.2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotropin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.