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Biomedical subjects

R Best

Publications and source records attributed to R Best.

At least 19 recordsLinked to original sources

Bilateral third and unilateral sixth nerve palsies as early presenting signs of metastatic prostatic carcinoma.

PURPOSE: To report four cases of cranial nerve palsy, which presented to the ophthalmologist as the only or one of the earliest manifestations of prostatic carcinoma. This is an infrequent complication of metastatic prostatic carcinoma usually only occurring late in the disease process in those with a history of prostatic carcinoma. METHODS: The case records of four patients with a history of a cranial nerve palsy who attended the ophthalmology department and who had a recent or subsequent diagnosis of prostatic carcinoma were reviewed. RESULTS: Diplopia caused by lesions affecting the third and sixth nerves sometimes in association with sensory symptoms may be a manifestation of metastatic prostatic carcinoma. These findings are consistent with base of the skull metastases from the condition. Two patients are still alive 54 months and 12 months after the diagnosis. One of the patients died 13 months after the diagnosis of prostatic carcinoma was made and the other died 21 months after the diagnosis from an unrelated hypertensive brain haemorrhage. CONCLUSIONS: Any patient presenting with diplopia must have an adequate past medical history taken and in an elderly gentleman this should include symptoms of prostatic disease. If indicated urological referral and measurement of prostate specific antigen may be performed. In patients whose cranial nerve palsy is complicated by other sensory signs or those in whom no sign of recovery occurs in 2 months, a contrast CT scan asking for bone windows to be included may be helpful in delineating any pathology. Radiotherapy may be useful for the treatment of metastatic prostatic carcinoma causing cranial nerve palsies with some patients experiencing either complete or partial resolution of their symptoms. The effect of newer hormonal agents or chemotherapy on this aspect of the disease is not well documented in current literature.

Abducens Nerve Diseases↗

Test characteristics of the urine Gram stain in infants <or= 60 days of age with fever.

OBJECTIVE: The utility of the Gram stain for the preliminary diagnosis of urinary tract infections (UTI) in infants or= 38.0 degrees C presenting to a pediatric emergency department during 2 consecutive winter seasons. Single pathogen growth of >or= 10(4) cfu/mL from a catheterized specimen and >or= 10(3) cfu/mL from a suprapubic specimen was considered positive. A positive Gram stain was defined as the identification of any organisms. Urinalysis was tested for the presence of nitrites and for leukocyte esterase (LE). Urine microscopy was analyzed for white blood cells per high power field (WBC/hpf). RESULTS: Fourteen of 246 patients were excluded; 11 because no Gram stain was completed. Of the remaining 232 patients, Gram stain had a sensitivity of 85.2% (95% CI 71.9-98.6%), a specificity of 99.0% (95% CI 97.7-100%), a likelihood ratio for a positive test of 87.3 (95% CI 21.8-349.9), and a likelihood ratio for a negative test of 0.15 (95% CI 0.06-0.37). There were 193 specimens for which a Gram stain and a complete UA and microscopy were completed and compared. Urine microscopy had a lower sensitivity and specificity than Gram stain for both >or= 5 WBC/hpf and >or= 10 WBC/hpf. In addition to the Gram stain, a dipstick negative for nitrites and LE had a low negative likelihood ratio (0.16), useful for decreasing the likelihood of a UTI. CONCLUSIONS: The Gram stain has excellent test characteristics for the preliminary diagnosis of a UTI in febrile infants. Patient disposition and therapy will likely change if clinical protocols and guidelines use the Gram stain rather than urine microscopy for preliminary diagnosis of UTI in infants.

Female↗

Silicone oil-intraocular lens interaction: which lens to use?

AIM: To determine a suitable intraocular lens for implantation in patients at high risk of lens exposure to silicone oil in their lifetime. METHODS: PMMA, AcrySof, AR40, AQUA-Sense, and Raysoft lenses were examined. Each lens was immersed for 5 minute intervals in balanced salt solution (BSS), in stained silicone oil, and again in BSS before being photographed in air and in BSS. Percentage silicone oil coverage of the lens optic was determined. RESULTS: The mean percentage coating (MPC) for the lens biomaterials ranged from 5.2% to 21.5%. The Raysoft lens had significantly less oil coverage when statistically compared with the other lens types (p < 0.001). CONCLUSION: A Raysoft (Rayner) lens is a suitable lens for implantation in patients who are at risk of severe vitreoretinal disease.

Adhesiveness↗

Population-based, case-control study of blood C-peptide level and breast cancer risk.

Insulin resistance has been suggested to be associated with an increased risk of breast cancer. Insulin sensitivity can be measured using blood C-peptide, a marker of insulin secretion. It is thus conceivable that blood C-peptide levels may be associated with breast cancer risk. To evaluate this hypothesis, we analyzed data from a subset (143 case-control pairs matched by age and status of menopause) of women who participated in the Shanghai Breast Cancer Study, a population-based, case-control study conducted in Shanghai during 1996-1998. Fasting blood samples were collected from study subjects to measure C-peptide levels. For cancer patients, the samples were collected before any cancer therapy. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals related to C-peptide levels. Breast cancer risk was increased with increasing levels of C-peptide (trend test, P = 0.01), with an odds ratio of 2.7 (95% confidence interval = 1.2-5.9) observed for the highest compared with the lowest tertile of C-peptide concentration after adjusting for body mass index and age at the first live birth. The risk was not altered after fully adjusting for other traditional risk factors for breast cancer. This positive association was observed in both pre and postmenopausal women and regardless of the levels of waist-to-hip ratio or body mass index. The results from this study were consistent with the insulin-resistance hypothesis for breast cancer and suggest that increased levels of C-peptide may contribute to the development of breast cancer.

Adult↗

Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population.

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospital's contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mother's Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.

Journal Article↗

Intergenerational and environmental factors influencing pregnancy outcomes.

PURPOSE: Factors that relate to the mother's own course of growth and development might influence later reproductive performances. This study examines the effect of maternal birth weight and maternal height and maternal weight gain, on term-small for gestational age (SGA) and preterm delivery.METHODS: Data used for this study were from the South Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) and birth certificate files for 1993-1995. Since PRAMS data were weighted to adjust for sampling probabilities, non-response and survey design, Survey Data Analysis (SUDAAN) software was used in all analyses.RESULTS: Maternal birth weight was strongly associated with term SGA (OR = 3.65; 95% CI = 1.83-7.29), but not preterm delivery among black mothers; it was associated with preterm delivery (OR = 1.86; 95% CI = 1.09-3.17), but not term-SGA for white mothers. Maternal birth weight was associated with term SGA among nonsmokers only (OR = 2.34; 95% CI = 1.33-4.11). Maternal weight gain modified the effect of height on birth outcomes. Among women with inadequate weight gain, there was a 3-fold increase in risk for term-SGA (OR = 3.06; 95% CI = 2.41-3.89) for short maternal height, but not for preterm delivery. Among women with adequate plus weight gain, the association between short maternal height and term-SGA was 2.7 (95% CI = 0.55-9.43) compared to 3.67 (95% CI = 0.1.41-9.56) between short maternal height and preterm delivery. Maternal weight gain also modified the effect of maternal height on both outcomes for black mothers and for nonsmokers only.CONCLUSIONS: Findings indicate the need for interventions directed to those women who can benefit most from appropriate targeted weight gain recommendations. Therefore, prevention methods should be implemented to encourage short stature women to gain adequate weight during pregnancy.

Journal Article↗

Methionine in the multifactorial etiology of neural tube defect affected pregnancies.

PURPOSE: Research in the last 40 years has provided evidence of the role of dietary nutrients in the development of NTDs. Failure of the neural tube to close is one of the most frequent and severe fetal developmental defects. The etiology of NTDs is complex encompassing genetic, dietary, and environmental factors. With regard to diet, it appears that in humans, a combination of low levels of methionine, folate, and Vitamin B(12) may lead to the occurrence of NTDs. The purpose of this study was to explore the relationship between maternal dietary intake of methionine and the risk of having a NTD affected pregnancy.METHODS: It was hypothesized that women with high maternal dietary methionine intake were at a decreased risk for NTDs. Combinations of methionine and folate without supplements, methionine and folate with supplements, and methionine and Vitamin B(12) and NTD risk were also examined. Data from a case-control study of 170 NTD-affected pregnancies and 269 controls were provided by a CDC sponsored NTD Surveillance, Prevention, and Research Project.RESULTS: There was an approximately 30-55% reduction in NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/day). The odds ratios (95% CI) associated with the 3 quartiles of methionine intake greater than 1580 mg/day after adjusting for Kcal, race, and BMI were 0.72 (0.4030-1.288), 0.68 (0.3390-1.347), and 0.45 (0.1830-1.088).CONCLUSIONS: These findings indicate a reduction in the risk of having a NTD affected pregnancy is associated with maternal periconceptional dietary intake of methionine.

Journal Article↗

Decline in prevalence of neural tube defects in a high-risk region of the United States.

OBJECTIVES: To conduct surveillance for neural tube defects (NTDs) in a high-risk region of the United States and to prevent occurrence and recurrence of NTDs through the periconceptional use of folic acid supplements. DESIGN: Active and passive methods were used for surveillance of NTD-affected pregnancies and births during a 6-year period (October 1992-September 1998). Individual genetic counseling was used to prevent NTD recurrences and a public awareness campaign was used to reduce NTD occurrences. SETTING: State of South Carolina. PATIENTS: All cases of spina bifida, anencephaly, and encephalocele identified among 278 122 live births and fetal deaths to South Carolina residents during 1992-1998 were included. MAIN OUTCOME MEASURE: Changes in occurrence and recurrence rates during a 6-year period. RESULTS: Over the 6 years of surveillance, the prevalence rates for NTDs decreased from 1.89 to.95 cases per 1000 live births and fetal deaths. The prevalence decrease is explained primarily by a decrease in cases of spina bifida. Isolated NTDs accounted for 297/360 (82%) NTDs and 63/360 (18%) had at least 1 other structural anomaly. Females predominated among isolated NTDs but the sex distribution was equal among NTD cases with other anomalies. Prevalence rates for whites (1.48 cases per 1000 live births and fetal deaths) were higher than rates for blacks (.87 cases per 1000 live births and fetal deaths). There were no NTD recurrences in 113 subsequent pregnancies to mothers of infants with isolated NTDs who took periconceptional folic acid. The rate of periconceptional folic acid use among women of childbearing years increased from 8% to 35% during the 6-year project period. CONCLUSION: The prevalence of NTDs in a high-risk region has declined coincident with the increased periconceptional use of folic acid supplements among women of childbearing age.neural tube defects, high-risk region, birth defects, folic acid, spina bifida, anencephaly, encephalocele.

Adolescent↗

Expression of p53 and mdm2 mRNA and protein in colorectal carcinomas.

The aim of our study was to investigate the expression of p53 and mdm2 mRNA and protein in colorectal adenocarcinoma. For the detection of mRNA, 60 fresh frozen human tumour samples and 12 samples of corresponding normal tissue were examined. After total RNA extraction, reverse transcription (RT) was performed followed by cDNA amplification with specific primers using RT-polymerase chain reaction (PCR). Immunohistochemical detection of protein was examined in 81 formalin-fixed and paraffin-embedded human tumour specimens as well as 15 samples of adjacent normal colorectal tissue. p53 mRNA was detected in 80% (48/60) of the tumours and in 67% (8/12) of normal tissue samples; 87% (52/60) of tumours had mdm2 mRNA in contrast to only 17% (2/12) of normal tissue specimens. Nuclear p53 protein expression was observed in 52% (42/81) of the tumour specimens and in none of the 15 normal specimens, whereas mdm2 protein was found in the nucleus (31%, 25/81) and also in the cytoplasm (86%, 70/81) of tumour samples. In normal tissue, mdm2 protein expression was only observed in the cytoplasm (13%, 2/15) and not in the nucleus. There was a significant correlation between coexpression of p53 and mdm2 protein and the occurrence of lymph node metastases (P = 0.03) as well as between p53 protein expression and the occurrence of distant metastases (P = 0.007). Additionally, significant associations were found between p53 mRNA and p53 protein, p53 mRNA and mdm2 mRNA or protein, and also between mdm2 mRNA and mdm2 protein expression, supporting the existence of a regulatory mechanism involving p53 and mdm2.

Adult↗

Assessment of the proliferation index in gastric carcinomas with the monoclonal antibody MIB 1.

Our study aimed to reveal whether the proliferation index of tumor cells, calculated with the monoclonal antibody (mAb) MIB1, is of prognostic relevance in patients with a gastric carcinoma and shows any correlation to well-known clinicopathological factors (TNM categories, stage, grade, Laurén type). We examined formalin-fixed, paraffin-embedded tissue blocks of samples from 94 patients, who underwent surgery for an adenocarcinoma of the stomach between 1988 and 1991. Specimens were immunohistochemically stained using the mAb MIB1 in combination with the alkaline-phosphatase/anti-(alkaline phosphatase) technique. The proliferation index (PI) was estimated in various areas of interest (tumor center and periphery and in lymph node metastases of compartments I and II), by always counting 200 tumor cells in three different high-power fields per specimen, and calculated as the percentage of MIB1-positive tumor cell nuclei relative to all tumor cell nuclei in the area examined. The total PI in the primary tumor was 47.2% and slightly higher in the center (49.1%) compared to the periphery (44.7%). Surprisingly in lymph node metastases the PI was lower than in the primary tumor (compartment I: 39.5%, compartment II: 33.6%). Tumors with distant metastases revealed a higher proliferative activity (55.1%) than tumors without (44.3%). The PI increased significantly from well to poorly differentiated carcinomas (P < 0.01), whereas the intestinal Laurén type showed a lower PI than the diffuse type. No difference in survival was found between patients with a median PI or less and those with a PI above the median (47.2%). Our results show that the proliferation index in gastric carcinomas has no prognostic relevance and therefore is of low clinical value.

Adenocarcinoma↗

11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress.

Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), which interconvert active corticosterone (cortisol in humans) and inert 11-dehydrocorticosterone (cortisone in humans). 11beta-HSD type 2, a dehydrogenase, thus excludes glucocorticoids from otherwise nonselective mineralocorticoid receptors in the kidney. Recent data suggest the type 1 isozyme (11beta-HSD-1) may function as an 11beta-reductase, regenerating active glucocorticoids from circulating inert 11-keto forms in specific tissues, notably the liver. To examine the importance of this enzyme isoform in vivo, mice were produced with targeted disruption of the 11beta-HSD-1 gene. These mice were unable to convert inert 11-dehydrocorticosterone to corticosterone in vivo. Despite compensatory adrenal hyperplasia and increased adrenal secretion of corticosterone, on starvation homozygous mutants had attenuated activation of the key hepatic gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, presumably, because of relative intrahepatic glucocorticoid deficiency. The 11beta-HSD-1 -/- mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis.

11-beta-Hydroxysteroid Dehydrogenases↗

Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone.

Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7alpha position. Brain extracts also efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy pregnenolone.

17-alpha-Hydroxypregnenolone↗

Prognostic relevance of occult tumor cells in lymph nodes of colorectal carcinomas: an immunohistochemical study.

PURPOSE: Whereas lymph node metastases in colorectal carcinoma are an important prognostic factor, the prognostic relevance of occult tumor cells in lymph nodes is not elucidated at present. Therefore, our study intended to assess the rate of patients with occult tumor cells in histopathologically negative lymph nodes. Furthermore, we tried to evaluate an eventual influence of these occult tumor cells on patients' prognoses. METHODS: For examination, we used paraffin blocks of lymph nodes, tumor-negative by conventional histopathology, from 49 patients with colorectal carcinoma (Stage I-III) after a curative (R0) tumor resection in 1987. After preparation of tissue blocks using the serial sectioning technique, the specimens were stained with the alkaline phosphatase, antialkaline phosphatase method and two monoclonal antibodies (AE1/AE3 and Ber-EP4). RESULTS: In 13 of 49 patients (26.5 percent), we disclosed tumor cells, mostly located in subcapsular sinuses as single cells or in groups. There was a good correlation between the detection rate and N category, tumor stage, and grading. Moreover, 33 percent of patients in Stage I/II with occult tumor cells (N0+) developed a local relapse and/or distant metastases in contrast to 12 percent of patients without tumor cells (N0-). With a median follow-up of 84 months, we found no difference in disease-free survival between the tumor cell negative and positive groups in Stage I/II patients. CONCLUSION: The results show that occult tumor cells might increase the risk for development of a local tumor relapse and/or distant metastases but do not influence patients' prognoses at all.

Adult↗

Force, velocity and energy dynamics of nine load-moving muscles.

Nine architecturally different muscles of the cat's hindlimb were investigated with respect to the kinetic energy, the potential energy, and the force variations associated with shortening contractions against gravitational loads. Insight about the energy dynamics of contractile muscle can provide a unifying concept for models of muscle performance capability. In this study, it was found that as contractions shortened from passive equilibrium against a constant mass load, acceleration and deceleration phases appeared. These phase were associated with muscular force variations of up to 25% of the mass weight in fast twitch muscles at low loads. In contrast, slow twitch muscles were associated with less than 10% force variations when shortening against a gravitational load. It also was found that optimal loads exist which maximize each muscle's ability to impart kinetic and potential energy, these optimal loads tend to be in the mid-force range for highly pennate muscle and in the low-force range for justform muscles. It was concluded that the kinetic energy provided by each muscle is a small percentage of that calculated from its length-force relationship, especially at low loads. This study confirms that the efficiency of kinetic energy conversion is very low at low loads (gradually improving as the loads increase) and thereby substantiates early experiments with heat and metabolic energy.

Animals↗