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Biomedical subjects

M Zimmerman

Publications and source records attributed to M Zimmerman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neutralizing anti-vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in a pre-clinical model.

PURPOSE: The formation of new blood vessels from the pre-existing vasculature is necessary for support of primary tumor growth and appears coincident with the development of metastasis. In previous studies, inhibition of vascular endothelial growth factor (VEGF), a potent angiogenic factor and mediator of vascular permeability, inhibited tumor neovascularization with consequent inhibition of both primary tumor growth and micrometastases when administered at the time of tumor inoculation. In the present study, we examined the effect of inhibiting VEGF on primary tumor growth and metastases in an in vivo model of established metastatic prostate cancer. MATERIALS AND METHODS: The human prostate cancer cell line DU-145 was found to secrete VEGF. DU-145.luciferase, a subclone stably transfected with an expression vector encoding the luciferase gene, injected subcutaneously, consistently formed tumors in C.B.-17 scid/scid mice. After 6 weeks, assay of whole lung lysates showed significant luciferase activity, consistent with the presence of micrometastasis. RESULTS: Twice weekly treatment of the animals with a monoclonal anti-VEGF neutralizing antibody, A4.6.1, not only suppressed primary tumor growth, but inhibited metastatic dissemination to the lung. When treatment was delayed until the primary tumors were well-established, further growth was still inhibited, as was the progression of metastatic disease. CONCLUSION: Inhibition of tumor-secreted VEGF by a neutralizing antibody is sufficient to significantly impair prostate tumor growth and its subsequent metastasis in an in vivo model of established advanced prostate cancer. These data suggest a critical role for VEGF in initiation and maintenance of tumor angiogenesis in prostate cancer. Inhibition of VEGF in patients with VEGF-secreting prostate cancers may prove an effective approach for inhibiting disease progression even after micro-metastatic dissemination has occurred.

Animals↗
PubMed1998

Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Our aim was to verify endoscopic ultrasound (EUS) accuracy to diagnose, rule out, and establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing ERCP for unexplained abdominal pain and/or suspected chronic pancreatitis underwent EUS. EUS was performed by experienced operators who were aware of the history but blinded to ERCP results. Chronic pancreatitis was defined using the Cambridge classification: 0 to 1 = "normal," 2 to 4 = "all chronic pancreatitis," 3 to 4 = "moderate to severe chronic pancreatitis." The number of EUS criteria required to obtain sensitivity, specificity, positive and negative predictive values > or = 85% was determined. EUS criteria for chronic pancreatitis are hyperechoic foci, hyperechoic strands, lobularity, hyperechoic duct, irregular duct, visible side-branches, ductal dilation, calcification, and cysts. RESULTS: One hundred twenty-six patients underwent EUS and ERCP. EUS was highly sensitive and specific (> 85%) depending on the number of criteria present. Chronic pancreatitis is likely (PPV > 85%) when more than two criteria (for "all chronic pancreatitis") and more than six criteria (for "moderate to severe chronic pancreatitis") are present. "Moderate to severe chronic pancreatitis" is unlikely (NPV > 85%) when fewer than three criteria are present. Independent predictors of chronic pancreatitis were "calcification" (p = 0.000001), history of alcohol abuse (p = 0.002), and the total number of EUS criteria (p = 0.008). CONCLUSIONS: EUS can accurately diagnose, rule out, and establish the severity of chronic pancreatitis found by ERCP.

Adult↗
PubMed1998

Oral manifestations in 100 Zimbabwean HIV/AIDS patients referred to a specialist centre.

OBJECTIVE: To document the prevalence, age, sex ratio and clinical features of oral lesions associated with HIV/AIDS among patients referred to the two largest specialist centres in Zimbabwe. DESIGN: Prospective study. SETTING: University Hospital. SUBJECTS: 100 consecutive patients with oral manifestations of HIV/AIDS were interviewed and examined by Dental Surgeons and Physicians. METHODS: Inspection and palpation of head and neck was done in all cases. Examination of the oral cavity and oropharynx with torchlight and wooden spatula was performed and lesions recorded according to WHO recording form for oral lesions possibly related to HIV infection. RESULTS: The median age was 35 years (range 19 to 66 years). The male to female ratio was 4:1. General symptoms and signs found were: weight loss in 52, diarrhoea in 34, lymphadenopathy in 21 and Herpes zoster in 12 patients. Ninety two patients had oral lesions of some sort. These consisted of: oral ulcerations in 26, candidiasis in 22, osteomyelitis in three, necrotizing gingivitis in two and herpetic gingivostomatitis in one patient. Neoplasms recorded were: Kaposi's sarcoma in 72 patients, squamous cell carcinoma in two patients. Four other tumours not associated with HIV/AIDS were found. No hairy leukoplakia was found in this study. CONCLUSIONS: The peak prevalence was in the age group 31 to 40 years with a male dominance of 4:1. The most frequent lesion was Kaposi's sarcoma, M:F ratio 3:1, followed by oral ulcers and candidiasis.

Adult↗
PubMed1997

Psychiatric screening in primary care: what do patients really want?

Psychiatric disorders are common in primary care, but underdiagnosed. U.S. physician reluctance to diagnose psychiatric illnesses is partly attributable to the belief that patients do not want their primary care physician to assess mental health. Six hundred one patients in a U.S. general internal medicine practice completed the SCREENER, a self-report questionnaire which screens for 15 psychiatric disorders, and another questionnaire about the SCREENER. Patients were predominantly female, unmarried, black, high school graduates. Only 3% thought that their physician should never evaluate their mental health. More than 60% desired periodic mental health screening, and one third wanted psychiatric assessment only when a problem was suspected. Attitudes toward questionnaire screening were less positive than toward physician interview. Patients were more likely to want screening if they were female, unmarried, young, had a history of mental health treatment, reported psychiatric symptoms, or were in fair-poor subjective physical or mental health.

Adult↗
PubMed1997

Anatomic reconstruction of the posterolateral cranial base with titanium micromesh for combined transpetrosal approach: technical note.

OBJECTIVE: We describe a new technique for the anatomic closure of the posterior petrosectomy defect after the combined supra-infratentorial transpetrosal approach for petroclival lesions. METHODS: With this technique, a titanium micromesh, tailored according to the defect of the drilled petrous bone and contoured to the outer appearance of the posterolateral cranial base, is used to cover the petrosectomy area. The mesh is fixed to the cranium and to the repositioned bone flap with titanium microscrews. RESULTS AND CONCLUSION: To date, this technique has proven to be simple and rapid and has been used in 10 patients who were operated on for various tumorous and vascular lesions of the petroclival region. Excellent cosmetic results were achieved, and no technique-related complications occurred.

Basilar Artery↗
PubMed1997

Erosive tooth wear: prevalence and severity in Swedish winetasters.

Full-time Swedish winetasters test on average 20-50 different wines, nearly 5 days a week. As the pH of wines ranges from 3.0 to 3.6, there is a potential risk for tooth erosion. The aims of this study were to document the prevalence and severity of tooth erosion in qualified winetasters in relation to number of years of winetasting, salivary flow rate, and buffer capacity. The subjects comprised all 19 qualified winetasters (7 women and 12 men, aged 29-64 years employed in Stockholm by Vin & Sprit AB, the state-owned company marketing wines and spirits. At intraoral examination, tooth surface loss was registered and documented by photography. Salivary flow rate and buffer capacity of unstimulated and stimulated saliva were measured. Data on occupational background and dental and medical histories were collected. Fourteen subjects had tooth erosion, the severity varying from mild to extreme, mainly on the labio-cervical surfaces of maxillary incisors and canines. The severity of the erosion tended to increase with years of occupational exposure. Caries activity in all subjects was low. 14 subjects had low unstimulated salivary flow rates. It was concluded that full-time winetasting is an occupation associated with increased risk for tooth erosion.

Adult↗
PubMed1996

Change in trabecular architecture as measured by fractal dimension.

The objective of this work was to expose dried trabecular bone material to a decalcifying environment and to quantify the change in the spatial distribution of the bone with a fractal measure. Digitized radiographic images were produced from four separate slices of human vertebral bone as they dissolved within a solution of nitric acid. Pixel data from a region of interest (ROI) within the trabecular bone were used to estimate the time-dependent change in fractal dimension of the ROI as the bone dissolved. Results demonstrated that a change in the spatial distribution of trabecular material may be expressed in terms of a concurrently changing estimate of the fractal dimension.

Algorithms↗
PubMed1996

Primary care patients' reactions to mental health screening.

OBJECTIVE: The authors examined whether there is empirical support for the notion that medical patients are upset by being asked questions about psychiatric disorders. METHOD: Six hundred and one patients attending a primary care clinic completed the SCREENER-a newly developed, brief self-administered questionnaire that surveys a broad range of psychopathology. In addition, they completed a second questionnaire that assessed their attitudes toward the SCREENER. RESULTS: We found a high level of acceptance by patients. The questions were judged easy to answer, and they rarely aroused significant negative affect. Fewer than 2 percent of the patients judged the questions difficult to answer, and fewer than 3 percent were "very much" embarrassed, upset, annoyed, or uncomfortable with the questions. Individuals with a history of psychiatric treatment and poorer current mental health reacted more unfavorably to the questionnaire. CONCLUSIONS: From the patient's perspective, it is feasible and acceptable to use self-administered questionnaires for routine screening of psychiatric problems in primary care settings.

Adult↗
PubMed1995

Increase in neuronal Jun immunoreactivity and epidermal NGF levels following UV exposure of rat skin.

Effects of cutaneous ultraviolet (UV) irradiation on superficial nerve fibres are controversial. In the present study we demonstrate by electron microscopy that single high-dose UV exposure of rat skin results in membrane damage in peripheral nerves. Furthermore, a UV-induced accumulation of nerve growth factor (NGF) within the irradiated epidermis and a delayed increase in nuclear Jun immunoreactivity in dorsal root ganglion neurones were detected by immunohistochemistry. Our results suggest that UV-mediated alterations of axonal membranes leads to an activation of Jun transcription factor within affected neurones despite an increase in neurotrophic NGF within their innervation area.

Animals↗
PubMed1995

Calcitonin gene-related peptide, substance P and nitric oxide are involved in cutaneous inflammation following ultraviolet irradiation.

Evidence from our previous work suggests that neurogenic mediators contribute to the inflammation following ultraviolet (UV) irradiation of the skin. We have investigated whether calcitonin gene-related peptide (CGRP), substance P and nitric oxide (NO) participate in the cutaneous inflammatory reaction of the rat hind paw and ear to UV irradiation. Skin blood flow was measured by laser Doppler technique. Oedema was quantified using a spring loaded micrometer to measure ear thickness. UV irradiation of the rat skin lead to a long lasting increase in skin blood flow. This increase was dose dependently attenuated by the CGRP receptor antagonist CGRP-(8-37) (0.15 nmol in 25 microliters to 6.0 nmol in 25 microliters, s.c.) up to 51% with a maximum of effectiveness at 24 h post irradiation. The inhibitor of NO synthase NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 25 nmol in 25 microliters, s.c.) attenuated skin blood flow by 38%. Concurrent injections s.c. of CGRP-(8-37) (1.5 nmol in 12.5 microliters) and L-NAME (25 nmol in 12.5 microliters) demonstrated an augmentive effect in attenuating skin blood flow. The tachykinin NK1 receptor antagonist CP-96,345 (6.0 nmol in 25 microliters, s.c.) attenuated skin blood flow by 27%. NG-Nitro-D-arginine methyl ester hydrochloride (D-NAME) and CP-96.344 showed no effects on skin blood flow after UV irradiation. CGRP-(8-37) (0.6 nmol in 10 microliters) i.d. and L-NAME (10 nmol in 10 microliters) i.d. had no effect of oedema formation after UV irradiation. Furthermore, post UV irradiation enhanced CGRP- and NO synthase-immunoreactivity in nerve fibres in the exposed skin area were visible. Taken these findings together we suggest the involvement of the neuropeptides CGRP and substance P and of neuronal NO on the vasodilatory component of the UV-induced inflammatory reaction of the rat skin. CGRP contributing to UV-induced vasodilation acts in an endothelial NO-independent manner.

Animals↗
PubMed1995

Suicidal ideation among urban medical outpatients.

The prevalence of current suicidal ideation among urban primary care outpatients was assessed, and suicidal and non-suicidal patients were compared with regard to their demographic characteristics and their attitudes toward mental health screening. Twenty (3.3%) patients reported having thoughts of killing themselves. The patients who had suicidal ideation were significantly younger and more frequently divorced. Almost all (97.6%) of the patients indicated that their physicians should inquire about emotional health issues at some time, and the suicidal patients were nonsignificantly more likely to recommend inquiry about psychiatric symptoms at every visit (55.0% vs 37.0%, p < 0.11). Only half of the suicidal patients reported lifetime histories of mental health treatment. The majority (70.2%) of the patients believed that it would be easy to discuss mental health problems with their medical physicians. Among the patients who had previously received psychiatric treatment, the suicidal patients were nearly three times more likely to anticipate that it would be difficult or very difficult to talk to their physicians about psychiatric problems. In contrast, among the patients who had no history of mental health treatment, there was no association between suicidal ideation and anticipated discomfort in talking with their physicians about emotional health.

Adult↗