Oral cytologic screening in a large metropolitan area.
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Computers↗
Biomedical subjects
D Murray
Publications and source records attributed to D Murray.
Cortisol binding to plasma proteins in man in health, stress and at death.
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17-Hydroxycorticosteroids↗
Does verapamil act as an immunomodulatory drug in vivo?
Based on in vitro data, previous investigators have hypothesized that Ca2+ entry blockers might affect lymphocyte activation, proliferation and effector function. We have tested this hypothesis by comparing the in vitro and in vivo effects of the Ca2+ entry blocker verapamil on human lymphocytes. In vitro high concentrations of verapamil (100 microM) inhibited mitogen-stimulated Ca2+ influx, inositol phosphate generation, and proliferation; similar effects were observed with diltiazem and nifedipine. In vivo treatment of healthy volunteers with verapamil (2-4 times 240 mg per day for 7 days) did not affect the number of circulating lymphocytes or their subset distribution. Moreover, we did not observe any effect of in vivo treatment with verapamil on mitogen-stimulated lymphocyte proliferation or expression of interleukin-2 receptors in vitro. We conclude that the inhibitory effects of verapamil on lymphocyte activation in vitro are unlikely to be of therapeutic relevance and may not be related to the Ca2+ entry blocking effects of this drug.
Adjuvants, Immunologic↗
Propranolol treatment affects parameters of human immunity.
Elevated sympathetic activity can modulate parameters of immunity. We investigated the role of the low sympathetic activity in resting healthy volunteers by treating them with the beta-adrenergic antagonist propranolol (3 x 40 mg/d for 7 days). Propranolol treatment increased the number of circulating T cells but not that of other white blood cells. Similarly, Con A-stimulated lymphocyte proliferation and IL-2 formation were enhanced. Although the number of circulating NK cells did not change, NK-cell activity was reduced markedly after propranolol treatment. These alterations are not a mirror image of the changes observed under conditions of elevated sympathetic activity but demonstrate that withdrawal of the endogenous sympathetic tone by drugs such as propranolol can modulate parameters of human immunity.
Adult↗
Increasing workload of an HIV/AIDS counselling service in a London teaching hospital, 1990-91.
The number of new patients referred to the HIV/AIDS Counselling Unit at the Royal Free Hospital, London, increased from 926 in 1989-90 to 1450 in 1990-91. Follow-up contacts nearly doubled during the same period of time. Growing demand for HIV testing as well as the shift to the treatment of HIV as a chronic condition increased the workload of the HIV/AIDS counsellors.
AIDS Serodiagnosis↗
Collaboration works in Northern Michigan.
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Community-Institutional Relations↗
DNA double-strand break rejoining in human follicular lymphoma and glioblastoma tumor cells.
Follicle center cell lymphoma is among the most radioresponsive of human cancers. To assess whether this radioresponsiveness might be a result of a compromised ability of the tumor cells to accomplish the biologically-effective repair of DNA double-strand breaks (DSBs), we have measured i) the extent of the mechanical rejoining of radiation-induced DSBs in biopsy-derived follicle center cell lymphoma cells and ii) the fidelity with which nuclear protein extracts from these cells rejoin restriction enzyme-induced DSBs. Cell suspensions derived from two lymphoma biopsies, designated FCL1 and FCL2, as well as two established human glioblastoma cell lines, M059J and M059K, were exposed to 30 Gy of gamma-rays and evaluated for their ability to rejoin DSBs using a Southern transfer-pulsed-field gel electrophoresis assay. The fidelity of rejoining of restriction enzyme-induced DSBs was assessed using a cell-free plasmid reactivation assay. Both lymphoma suspensions rejoined DSBs relatively slowly and exhibited a similar phenotype to the known DSB-rejoining deficient M059J line. The level of DSB mis-rejoining in the cell-free plasmid reactivation assay was also similar in M059J and FCL2 cells and was considerably ( approximately 6-fold) higher than in M059K cells. Because of insufficient numbers of cells, we were unable to perform this assay with the FCL1 lymphoma. These limited data suggest that follicle center cell lymphoma cells may be intrinsically deficient in performing the biologically-effective rejoining of DSBs. Such a deficiency might contribute to the radioresponsiveness of this disease and may be exploitable in the development of improved treatment strategies, such as radioimmunotherapy.
Brain Neoplasms↗
Who's holding the baby?--women's experience of their postnatal care.
This paper examines women's experience of their postnatal care in hospital and at home. It found that over a third of women surveyed had problems caring for themselves and the baby. Breastfeeding mothers were more likely to have problems than bottle-feeding mothers. There was no relationship between having such problems and parity. Women were particularly dissatisfied with postnatal services at home, 45% describing them as inadequate. Satisfaction with services was significantly associated with having sufficient advice from health professionals in hospital and at home. In view of the findings of this paper, it is clear that a strategy is required to identify those most in need of postnatal care and target services accordingly.
Adolescent↗
Sensitivity of nucleotide excision repair-deficient human cells to ionizing radiation and cyclophosphamide.
Nucleotide excision repair (NER)-deficient rodent and human cells (such as those derived from patients with xeroderma pigmentosum, XP) are hypersensitive to UV light. Some of these cell lines, specifically certain rodent mutants with severe defects in the ERCC1 and XPF genes, are dramatically sensitive to crosslinking agents such as phosphoramide mustard (PM). These crosslink-sensitive rodent mutants also exhibit sensitization to gamma-rays under hypoxic (but not under aerated) conditions. Like their rodent counterparts, human XP cells are highly sensitive to UV light; however, none of the human XP lines, even XPF, displays extreme hypersensitivity to crosslinking agents. Studying XP cells, therefore, allows us to further assess the extent to which the phenotypic characteristic of hypoxia-specific radiosensitization of mammalian cells tracks with defects in crosslink repair (as opposed to NER). The sensitivity to PM and gamma-rays of normal human fibroblasts and human XP fibroblasts from two complementation groups, XPA and XPF, was assessed using a clonogenic survival assay. Compared with normal cells, XPA cells were not appreciably hypersensitive to PM or to gamma-rays under either aerated or hypoxic conditions. XPF cells were modestly (approximately 1.75-fold) sensitive to PM but showed no significant radiosensitization under either aerated or hypoxic conditions. Thus, although the phenotype of human XPF cells is quite different from that of "severe" rodent XPF mutants such as UV41, the characteristic of hypoxia-specific radiosensitization consistently tracks with extreme hypersensitivity to crosslinking agents and is separable from UV sensitivity (and thus from defects in NER).
Biotransformation↗
Circadian variation in multiple sclerosis of oxidative stress marker of DNA damage. A potential cancer marker?
OBJECTIVE: To investigate circadian rhythm (CR) of urinary creatinine and 8-hydroxy-2-deoxyguanosine (8-OHdG) in patients with Multiple Sclerosis (MS) and to present concentrations of this DNA damage marker, 5 years prior to mastectomy, in one MS study subject, and 2 years prior to biopsy confirmed a carcinoma (CA) of the prostate in one non-MS subject. MATERIALS AND METHODS: Eleven subjects with MS (6 women 36-52 years of age and 5 men 51-68 years) volunteered for this study, carried out at Edward Hines Jr., Medical Center. Subjects were offered a general hospital diet (2400 cal in total/24h) at 16:30h, 07:30h and 13:00h. The dark (sleep) phase of the light-dark cycle extended from 22:30h to 06:30h with brief awakening for sampling at 01:00h, and 04:00h. Urine samples were collected for consecutive 3h spans beginning at 16:00-19:00h and were analyzed for creatinine and 8-OHdG. Twelve men (including 3 with type 2 diabetes) provided 21 profiles according to the same protocol used for comparison. In addition, 10 healthy women provided 24h urine samples. Statistical analysis of data was performed using the Single-Cosinor and Population-Mean Cosinor. RESULTS: A CR was detected for creatinine in healthy men (p < 0.001) but not for MS patients. Urinary creatinine concentrations were lower in MS women than in healthy women (p = 0.015) and were lower in MS women than in men healthy or with MS (p < 0.001): Women; MS 655 +/- 76; H 1381 +/- 316; Men, MS 1830 +/- 285; H 1532 +/- 265 mg/24h vol. A CR was evident in 8-OHdG in MS (p = 0.007) and in non-MS subjects (p < 0.001) with highest values occurring at about 16:45h. The average concentrations of 8-OHdG in MS patients were similar to those in healthy subjects: Women, MS 589 +/- 125; H 794 +/- 318; Men, MS 504 +/- 156; H 591 +/- 134 picomoles/kg bw/24h vol. The 8-OHdG concentrations of a MS patient, later diagnosed with breast cancer, were found to exceed the upper 95% prediction limit in health. An increased 8-OHdG level was also noted in a non-MS subject who 2 years later received a biopsy-confirmed diagnosis of prostate CA. CONCLUSIONS: Despite the small number of subjects in this study, a statistically significant CR was documented for 8-OHdG in urine of subjects with MS. Interestingly, the increased concentrations of DNA damage marker, the 8-OHdG, 5 years prior to mastectomy and the 2 years prior to affirmative diagnosis of prostate CA, could be the most significant clinical observations of this study. Follow-up studies of a larger population of subjects would, thus, be required to ascertain the predictive validity of such challenging observation.
8-Hydroxy-2'-Deoxyguanosine↗
Streptococcal sore throat followup program in a hospital clinic, New York City.
To improve followup and treatment of patients with streptococcal sore throat at St. Vincent's Hospital and Medical Center, New York City, a simple and inexpensive method was devised for recalling and treating untreated patients with positive throat cultures and culturing household contacts. The program was conducted by a clinic nurse and a secretary, with only occasional assistance from a physician. All services were free for those without Medicaid coverage. The secretary sent notification letters to all patients with positive cultures urging them to return for treatment and emphasizing the need for their contacts to come for screening. The secretary, trained in the throat culturing technique, also performed the laboratory work on the cultures from contacts. The clinic nurse swabbed the throats of all contacts and administered treatment, according to a standing-order protocol, to all with culture-proved streptococcal sore throat. A comparison of initially untreated patients with positive cultures seen 3 months before and 6 months after the program was started revealed that 46 percent returned for treatment after the notification letter was sent; before the program only 21 percent returned for treatment. No attempt had been made to reach household contacts before the program began. The rate of streptococcal sore throat in contacts was 14 percent, and in the clinic patients it was 11 percent during the first 6 months of the program.
Adolescent↗
Natural history of anterior knee pain: a 14- to 20-year follow-up of nonoperative management.
We describe a consecutive series of girls with idiopathic anterior knee pain in adolescence and who were treated nonoperatively. At a mean follow-up of 16 years, 22% had no pain, 71% thought that their symptoms were better than at presentation, 88% used analgesics rarely or not at all, and 90% continued to participate regularly in sports. Nevertheless, about one in four of the patients continued to have significant symptoms for < or = 20 years after presentation. No features were identified that predicted those patients in whom symptoms would persist. We conclude that surgical treatment of idiopathic anterior knee pain in adolescents is not justified until a procedure has been shown to provide a better outcome than that reported here or until a way has been found to distinguish the few patients who will not get better spontaneously from the majority who will.
Adolescent↗