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Biomedical subjects

R Grimson

Publications and source records attributed to R Grimson.

At least 37 records · Page 2Linked to original sources

A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings.

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

Adult↗

Plasma assay of gelatinase B: tissue inhibitor of metalloproteinase complexes in cancer.

BACKGROUND: Matrix metalloproteinases (MMPs), especially gelatinase A and gelatinase B (GLB), are believed to be important components of the metastatic process. Tissue Inhibitors of Metalloproteinases (TIMPs) form complexes with MMPs and inhibit cancer dissemination. After local secretion, MMPs and their complexes with TIMPs leach into the blood stream where their concentration can be measured, thereby serving as surrogate markers of disease. Elevated plasma gelatinase B levels have been detected in gastrointestinal cancer and breast cancer. The goal of this study was to determine whether plasma GLB:TIMP complexes also are increased in cancer and whether these tests have potential use as prognostic tumor markers. METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed to measure the plasma concentration of GLB:TIMP complexes in patients with cancer. Correlation between ELISA results and clinical outcome was sought. RESULTS: Plasma GLB:TIMP complexes were significantly increased in patients with gastrointestinal cancer and gynecologic cancer, but not in patients with breast cancer. When results from plasma GLB:TIMP complexes and plasma GLB assays were combined (GLB/complexes), abnormal levels of one or both assays were found in 36% and 65% of patients with gastrointestinal and gynecologic cancer, respectively. In Stage IV gastrointestinal cancer, patient survival was shorter (P < 0.001) in the group with increased plasma GLB/complexes than for those with normal plasma levels (4 months vs. 20 months, respectively). CONCLUSIONS: The assay of plasma gelatinase B and GLB:TIMP complexes may be clinically useful in predicting survival in subsets of patients with cancer. The possibility of using these assays in early stage cancer to predict metastasis should be studied.

Biomarkers, Tumor↗

The use of cohort vs repeated cross-sectional sample survey data in monitoring changing breast cancer screening practices.

BACKGROUND: The method used to select a study sample is a key element in designing a research protocol. This article explores two of the more common methods used, focusing on the relative advantages and disadvantages of each one. METHODS: Both cohort and repeated, independent cross-sectional surveys were conducted in each of 3 years (1988-1990) in the Awareness of Breast Cancer Screening Project to follow changing breast cancer screening rates among a population of women 50-75 years of age on Long Island, New York. RESULTS: Both survey methods revealed statistically significant increases in self-reports of mammography use. The cohort and repeated cross-sectional survey sample responses to questions concerning knowledge, attitudes, and behavior regarding breast cancer screening were comparable. An educational effect of the baseline survey itself on the cohort was not seen. CONCLUSIONS: Each of the two survey methods has advantages and disadvantages with respect to the other. The cohort method permits examination of changes in the same individual over time and is less costly and less time-consuming to perform. On the other hand, the cross-sectional method does not suffer from cumulative losses in respondents with repeated surveys and better reflects the changing community. The study findings can be used to guide the selection of an appropriate survey methodology for monitoring breast cancer screening practices in other settings.

Aged↗

Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

Adolescent↗

Quantitation of human immunodeficiency virus type 1 during pregnancy: relationship of viral titer to mother-to-child transmission and stability of viral load.

To develop strategies to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), it is important to define the factors determining it. We examined the relationship between maternal HIV-1 titer and the occurrence of mother-to-child transmission. In addition, we quantitated HIV-1 longitudinally in mothers during pregnancy, at delivery, and up to 1 year postpartum. To examine transmission, we prospectively studied 19 mother-child pairs; in 5 pairs, HIV-1 transmission occurred. We used endpoint dilution culture of peripheral blood mononuclear cells to determine maternal viral titer and found that although 4 of 6 (67%) women with viral titers of > or = 125 HIV-1 infectious units per 10(6) cells transmitted HIV-1 to their infants, only 1 of 13 (7.6%) women with lower viral titers transmitted (P = 0.01). Twelve of the 19 mothers had HIV-1 loads determined serially 3-8 times over periods ranging from 18 to 65 weeks. Viral titers varied greatly between the 12 women, but the viral load in each woman remained stable over time. In this cohort, HIV-1 viral load remained stable during pregnancy and the greater the maternal viral burden, the more likely that transmission occurred. These two related findings suggest that determination of HIV-1 titers early in pregnancy may predict which women are at high risk of transmitting to their infants and may be used to counsel HIV-1-infected women of childbearing age. These data identify maternal viral titer as a major determinant of mother-to-child HIV-1 transmission and thereby provide the scientific rationale for therapeutic strategies designed to interrupt transmission by lowering viral load.

Acquired Immunodeficiency Syndrome↗

Primary graft failure: a case control investigation of a purported cluster.

Primary graft failure is a rare but major complication of penetrating keratoplasty. An apparent clustering of four cases during a 1-month period led to a review of all 778 keratoplasties performed by nine surgeons at Massachusetts Eye and Ear Infirmary from July 1, 1986 to June 30, 1988. The objectives of this study were (a) to investigate the possibility that cases of primary graft failure occurred in clusters within their physical environment of space, time, and personnel and (b) to determine the frequency of and evaluate possible risk factors for primary graft failure. Twenty-one cases of primary graft failure were found, resulting in an incidence rate of 2.7% during this period. A 13.3% incidence of primary graft failure was found in donor mates, suggesting improper tissue preparation. The charts and eye bank records of the 21 cases and 84 age-matched controls, randomly selected from the group of all keratoplasties, were reviewed for donor-, recipient-, surgeon-, and surgery-related characteristics. Improper tissue preparation was not associated with primary graft failure. An individual surgeon was the most significant risk factor [odds ratio = 6 (95% CI: 2.1-17.0)].

Adult↗

The use of mammography vans by low-income women: the accuracy of self-reports.

The objective of this study was to determine the accuracy of self-reports of mammography use by low-income income women. Mammography van records were used to verify self-reports of mammography use in the past year by women aged 50 through 75 years who had visited five community health centers (n = 237). Van records verified mammography use for 99% of these women (82% within the previous year and 98% within the past 2 years). Forty percent of those with van records who reported both the month and year of the mammogram were accurate. Inaccurately reported dates were more frequently after (74%) rather than before (26%) the actual date. These findings indicate that self-reports of mammography use by low-income women are generally reliable.

Aged↗

Prediction of sudden cardiac arrest: risk stratification by anatomic substrate.

The prognostic importance of coronary artery anatomy to specific outcomes including ventricular tachycardia/fibrillation was evaluated in 372 consecutive patients undergoing cardiac catheterization at University Hospital at Stony Brook between 1981 and 1984. The hypothesis that proximal left anterior descending artery narrowing before the first septal perforator had a specific relationship to survival was again tested in this cohort. The population was prospectively followed for 8 years, with all clinical management decisions made independently by the patient's primary or referring physician. Multivariate statistical and life table analyses were performed after comprehensive follow-up. Significant narrowing in the proximal left anterior descending artery was associated with an increased risk of sudden cardiac death (p = 0.0002). Abnormalities of contractility in the diaphragmatic segment of the left ventricle in addition to an elevation of the left ventricular end-diastolic pressure and the presence of congestive heart failure (p < 0.05) were other contributory variables. Outcome in patients with proximal left anterior descending coronary artery disease who underwent aortocoronary artery bypass to the artery demonstrated improved survival (p < 0.05). Risk stratification of patients at high risk for sudden cardiac death is possible and may allow identification for an aggressive approach or interventional trials.

Adult↗

Long HIV-1 incubation periods and dynamics of transmission within a family.

The incubation period of human immunodeficiency virus type 1 (HIV-1) infection was studied in a family of five in which vertical and heterosexual transmission occurred from one index case. This investigation documented incubation periods of longer than 12 years in a mother and her daughter; although neither has symptoms, both are definitely infected and have very low CD4(+)-lymphocyte counts. The study confirmed the predictions of incubation periods longer than 10 years in a small proportion of infected individuals. It provides evidence that vertically HIV-1-infected teenagers can be expected to appear in the population.

Acquired Immunodeficiency Syndrome↗

The effects on merino lambs of chronic infection with Trichostrongylus rugatus.

Four groups of six 5-month-old merino lambs were exposed to infection with 12,000 larvae of Trichostrongylus rugatus per week and one group was killed at each of 3, 6, 9 and 12 weeks. Numbers of adult worms increased in an approximately linear manner throughout the experiment; the percentage of larvae developing to adults remained between 35 and 25% throughout the course of the experiment. Sub-total villus atrophy was evident in the anterior small intestine of each group of infected sheep and significant reductions occurred in the plasma concentrations of albumin and phosphate. Serum globulin and calcium concentrations rose in infected animals. No clinical signs were observed in infected sheep, no alteration in bone histology was detected and no decrease in growth rate occurred.

Animals↗

Comparison of the effects of infection with Trichostrongylus colubriformis, T. vitrinus and T. rugatus in merino lambs.

Groups of six worm-free merino lambs were infected with 100,000 larvae of T. colubriformis, T. vitrinus, T. rugatus or a mixture of the three species and were slaughtered 21 days later. Nematodes were distributed predominantly in the first 3 m of the small intestine where they caused subtotal villus atrophy. T. vitrinus caused severe erosion of the epithelium; erosion was less severe with T. colubriformis infections and mild with T. rugatus infections. Plasma concentrations of albumin declined during the experiment and were most marked in sheep infected with T. vitrinus. Plasma phosphate concentrations declined during infection with all three species, while plasma concentrations of globulin and calcium declined only in sheep infected with T. vitrinus. Food intake was reduced in all groups, but was most marked with sheep infected with T. vitrinus. T. vitrinus appeared to be more pathogenic than the other species.

Animals↗

Comparison of antigen immunoassay and reverse transcriptase assay for monitoring human immunodeficiency virus infection in an antiviral trial.

We compared the Abbott enzyme immunoassay for human immunodeficiency virus (HIV) antigen with the reverse transcriptase assay (RTA) as a means of monitoring HIV infection during an antiviral trial. The Abbott enzyme immunoassay detected HIV earlier than RTA whether or not the patients were antigenemic and appears to be superior to RTA for detecting HIV in cultures used for monitoring clinical trials.

AIDS-Related Complex↗

Antibody to human immunodeficiency virus correlates with decreased T helper lymphocytes in asymptomatic individuals.

To examine the relationship between human immunodeficiency virus (HIV) seropositivity and T lymphocyte subsets in a clinically well population, we assayed HIV antibody and analyzed T lymphocyte subsets in 30 people at increased risk for acquired immunodeficiency syndrome (AIDS) who were clinically well. Seventy-six percent of the HIV-seropositive individuals had abnormally low numbers of T helper lymphocytes, and HIV seropositivity was strongly correlated with an abnormally low number of T helper cells (p less than 0.00002). Among these clinically well subjects at increased risk for AIDS, HIV-sero-positive individuals had a significant decrease in mean T helper lymphocytes and mean T helper:T suppressor ratios as compared to those who were seronegative (483 cells/mm3 vs 915 cells/mm3, p less than 0.002; and 0.80 vs 1.7, p less than 0.002, respectively). Because of the strong correlation of HIV seropositivity and abnormally low numbers of T helper lymphocytes in this asymptomatic population, these findings suggest that asymptomatic seropositive individuals should be followed closely for development of AIDS-related disease and should be considered for future antiviral therapy when it becomes available.

Acquired Immunodeficiency Syndrome↗

Herniorrhaphy in the elderly. Benefits of a clinic for the treatment of external abdominal wall hernias.

Elective abdominal herniorrhaphy carries morbidity and mortality rates of 26 percent and 1.5 percent, respectively, in patients over 65 years of age. These figures climb to 55 percent and 15 percent during emergent surgery. Our purpose was to investigate if standardization of treatment could improve such results. Our program stressed centralization of care in a hernia clinic; early operation of patients at risk of incarceration; optimization of underlying systemic disorders by consultative services; operation under local anesthesia; preoperative, operative, and postoperative protocol; and continuity of care by senior personnel. Over a 4 year period, we have performed 241 abdominal herniorrhaphies in patients over 65 years of age (median age 71.5 years old) who exhibited an 84 percent incidence of significant preoperative systemic disorders. Since the inception of our program, our rate of emergent operation has decreased significantly from 7 percent to 2 percent (chi-square less than or equal to 0.05). Our rate of systemic complications after elective operation was 1.2 percent and 0 after emergent operation. These data are statistically better than those reported in the literature (chi-square less than or equal to 0.05). These results suggest that the creation of a hernia clinic significantly improves the care of herniated patients.

Age Factors↗

ras p21 expression in the progression of breast cancer.

The differential expression of the ras oncogene product p21 in the primary tumor, regional nodes, and distant metastatic sites in patients with disseminated breast cancer was examined to define the biologic and clinical significance of the ras oncogene in the progression of breast cancer. The avidin-biotin peroxidase complex method was used on formalin-fixed, paraffin-embedded tissues from 16 patients with metastatic disease. The primary antibody used in this protocol was RAP-5, an anti-p21 murine monoclonal IgG2a. p21 antigen staining was similar in the primary tumor and regional nodes from the same patient (P less than 0.05), but the staining of distant metastases was more variable. Expression of ras p21 was consistently increased in invasive components of the primary tumor as compared with intraductal tumor. In addition, a high level of p21 expression was seen in tumor emboli in lymphatics and blood vessels as compared with contiguous tumor in parenchymal tissue. Although p21 staining is present in aggressive primary breast cancers and most metastatic sites, our findings indicate that markedly enhanced p21 expression is associated with the earlier stages (invasion and dissemination) of aggressive breast cancers.

Breast Neoplasms↗

Pregnancy- and gender-related changes in pulmonary vascular reactivity.

Pregnancy is a state of altered pulmonary vascular reactivity, but the conclusions about changes in reactivity have varied with the agents or species chosen for study. The present study was designed as a comprehensive analysis of pregnancy-induced and gender-related differences in pulmonary vascular reactivity in one species. Using an isolated perfused feline lung preparation, the pulmonary vascular responses to angiotensin II, serotonin, histamine, epinephrine, norepinephrine, and acute hypoxia (FIO2, 8%) were compared between males, females, and pregnant females. Vascular reactivity (maximum response) and drug sensitivity (ED50) were compared using cumulative dose-response data for each pharmacological agent. The results demonstrate that (1) reactivity to angiotensin II, serotonin, epinephrine, and acute hypoxia is decreased during pregnancy, while the response to norepinephrine remain unchanged, (2) drug sensitivity is unchanged with serotonin and the catecholamines, increased with histamine, and decreased with angiotensin II, and (3) the responses to acute hypoxia and histamine have significant gender-related differences in reactivity independent of the changes observed during pregnancy.

Angiotensin II↗

Ocular sarcoidosis. A case-control study among black patients.

A case-control study was conducted to investigate possible environmental risk factors for ocular sarcoidosis. The factors studied were exposures to pine products and occupational histories of employment in the tobacco, lumber, and textile industries. The exposure histories of 29 female and 15 male cases, patients with newly diagnosed ocular sarcoidosis that were attending the Glaucoma/Uveitis Clinic of the North Carolina Memorial Hospital, were compared to those of 110 female and 28 male controls selected from out-patient clinics. Elevated risks for sarcoidosis were detected among those females that were exposed to burning pine or were employed in the tobacco industry. For males, positive associations were observed for chewing pine products and for employment in the lumber and textile industries. These preliminary data are consistent with incomplete phagocytic clearance of nonbiodegradable foreign bodies present within our environment that may become antigenic to the immunologically susceptible host. Confirmation of refutation of these hypotheses awaits additional clinical and epidemiological research within the sarcoidosis belt.

Adolescent↗

Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients.

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers.

Antibodies, Monoclonal↗