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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1995

Vasoactive intestinal peptide and nerve growth factor effects on nerve regeneration.

Sixty rat sciatic nerves were used to study the effects of vasoactive intestinal peptide (VIP) and nerve growth factor (NGF) on nerve regeneration. They were divided into three groups. Groups 1 and 2 were treated with VIP and NGF, respectively, after dividing the nerves without repair and placing them in silastic chambers. Group 3 served a control. The rate and quality of nerve regeneration were compared among the groups using caliper measurements and histologic evaluation. Both VIP and NGF groups showed an enhanced rate of regeneration at three weeks as compared to controls (p < 0.05). The quality of nerve regeneration histologically and by axonal counting was not significantly different among the three groups, except for the presence of less vascularity in the VIP as compared with the NGF group. In addition to NGF, VIP appears to increase the rate of nerve regeneration as compared to controls.

Animals↗
PubMed1995

Screening for Wilms tumor in high-risk individuals.

Recognition of the association between a variety of genetic syndromes and Wilms tumor has influenced physicians to develop tumor surveillance protocols based on empiric risk estimates. In recent years, clinical evaluation of high-risk individuals has been greatly refined and sensible screening protocols have been proposed. A continued effort to clinically characterize the Wilms tumor syndromes continues to be important, and a patient registry is currently being generated by one of the authors (CC). This registry will prospectively assess the occurrence of Wilms tumor in patients with high-risk phenotypes. All interested clinicians are encouraged to enroll their patients. As molecular genetic technologies refine our knowledge of factors leading to Wilms tumor, improved mechanisms of surveillance in high-risk individuals will be developed. Recent characterization of molecular mechanisms responsible for cases of BWS, isolated hemihypertrophy, DDS, familial Wilms tumor, and aniridia has already influenced the clinical management of high-risk patients and has become an important adjunct to clinical assessment in these patients. The involvement of clinical genetics in the coordination of clinical assessment, genetic testing, and tumor surveillance will provide better patient care and will promote the development of a multidisciplinary approach to Wilms tumor risk assessment. This collaboration between clinical genetics, molecular biology, oncology, and pediatrics should allow for a more precise understanding of tumor risks and will accelerate the understanding of factors involved in the genesis and progression of Wilms tumor.

Humans↗
PubMed1994

Neurobehavioral characteristics of CGG amplification status in fragile X females.

Neurobehavioral correlates of CGG amplification were studied in 17 nonretarded adult female carriers of fragile X syndrome. The results revealed a significant relationship between IQ and the number of CGG repeats in the 5' untranslated region of the FMR1 gene. Women with a full mutation (> 200 CGG repeats) scored below average in IQ, visual-spatial perception, visual-spatial organization, and executive function. There were no differences in fine motor dexterity or memory as a function of CGG amplification status. A history of major depressive disorder was identified in 71% of the sample, but incidence of depression was not associated with the degree of CGG amplification. Schizotypal features were noted in 18%. No intellectual or neuropsychological deficit was found in women with a premutation (< 200 CGG repeats). Decrements in IQ, visual-spatial perception, and executive function appear to arise as a consequence of the CGG amplification.

Adult↗
PubMed1994

Megestrol acetate for the prevention of hot flashes.

BACKGROUND: Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. METHODS: The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries. RESULTS: After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). An intention-to-treat analysis of data for all eligible treated patients showed that 74 percent of the megestrol acetate group, as compared with 20 percent of the placebo group, had a decrease of 50 percent or more in the frequency of hot flashes during the first four weeks (P < 0.001). The degree of efficacy was similar in men and women. The only side effect was withdrawal menstrual bleeding in women, generally occurring one to two weeks after the megestrol acetate had been discontinued. CONCLUSIONS: Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.

Breast Neoplasms↗
PubMed1994

Repair of failed transpedicle screw fixation. A biomechanical study comparing polymethylmethacrylate, milled bone, and matchstick bone reconstruction.

In a random, controlled laboratory study, pedicle screws placed in human cadaveric vertebrae were axially loaded to failure. Three repair methods were tested. Use of low pressure polymethylmethacrylate yielded 149% of the original pullout strength, milled bone yielded 70% of the initial pullout strength, and matchstick bone yielded 56% of the initial pullout strength. Two incidents of cortical penetration during reinsertion in the matchstick group occurred. The results were statistically analyzed.

Biomechanical Phenomena↗
PubMed1994

Autocrine stimulation of B lymphocytes by a platelet-activating factor receptor agonist, 1-palmitoyl-2-acetyl-sn-glycero-3-phosphocholine.

Based on previous data which demonstrated the ability of platelet-activating factor (PAF) antagonists to inhibit constitutive immunoglobulin synthesis in B-lymphoblastoid cell lines, we determined the capacity of these cells to synthesize PAF or 1-palmitoyl-2-acetyl-sn-glycero-phosphocholine (PAGPC), an acyl-PAF identified in various cell types. In two B-lymphoblastoid cell lines (LA350 and HSCE-), significant amounts of production of PAGPC were detected, whereas the amount of PAF was below the level of detection in our system. The biologic effects of PAGPC were examined in these cells, both of which have well-characterized PAF receptors. PAGPC induced a concentration-dependent increase in intracellular Ca2+ concentrations and activation of MAP-2 kinase (as detected by immunoblotting and measurements of kinase activity) in these cells. The kinetics and magnitude of these responses were similar to those induced by PAF, and they were inhibited by Web 2086, a PAFR antagonist. Phosphatidylcholine, which differs from PAGPC in that it contains a long fatty acid residue at position 2, did not induce any of these responses. A mutual cross-desensitization of the B lymphoblasts between PAGPC and PAF was observed for Ca2+ mobilization. To induce maximal cell stimulation, approximately 600-fold higher concentrations of PAGPC than of PAF were needed. Because the two B-lymphoblastoid cell lines synthesized significant amounts of PAGPC, this phospholipid may participate in an autocrine stimulation pathway in B cells. Furthermore, the data indicate that PAGPC is an agonist for the PAFR in B lymphoblasts and that the ether linkage in the PAF molecule is not an absolute requirement for activity, although it increases the potency of the ligand.

Amino Acid Sequence↗
PubMed1994

Putative tumor-suppressor gene on chromosome 11 is important in sporadic endocrine tumor formation.

Endocrine tumors arising sporadically or as a manifestation of the multiple endocrine neoplasia type I syndrome (MEN I) have been shown to have mutations on chromosome 11. These mutations can be detected at the molecular level by loss of heterozygosity (LOH) for DNA markers from chromosome 11. This study represents one of the largest collections of sporadic endocrine tumors in which LOH was systematically assessed on chromosome 11 for the loci flanking the proposed MEN I region. DNA was isolated from 39 endocrine tumors and probed with 7 DNA probes spanning the region of chromosome 11q13 from the loci PYGM to INT-2. Eleven tumors demonstrated LOH at any two loci in this region. The remaining 28 tumors showed no LOH or were noninformative at these loci. Thus, nearly 30% of these tumors showed LOH in the region (from PYGM to INT-2) that is thought to contain the MEN I gene(s). Previous studies of sporadic endocrine tumors have suggested that these tumors may arise via the same mechanism as tumors of the MEN I syndrome. Namely, these sporadic tumors are thought to result from mutations leading to genetic loss on the long arm of chromosome 11, thereby inactivating a possible tumor-suppressor gene (or genes). These findings strongly support the hypothesis that sporadic pancreatic endocrine tumors share a similar etiology of tumorigenesis with tumors of the MEN I syndrome, which principally involves deletion of a tumor-suppressor element (or elements).

Blotting, Southern↗
PubMed1994

Risk stratification using the Society of Thoracic Surgeons Program.

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.

Aged↗
PubMed1994

The association of alcohol and night driving with fatal snowmobile trauma: a case-control study.

STUDY OBJECTIVE: To investigate the association of alcohol use and night driving with traumatic snowmobile fatalities. DESIGN: Case-control study. PARTICIPANTS: Traumatic deaths occurring while driving a snowmobile during the years 1985 to 1990 were reviewed. A sample of 1989 to 1990 fatal motor vehicle driver and motorcycle driver accidents were used as controls. Records were obtained from the provincial coroner. RESULTS: One hundred eight snowmobile fatalities, 432 motor vehicle fatalities, and 108 motorcycle fatalities were included. Young men (mean age, 30 years) made up the snowmobile fatalities population, with weekend fatalities predominating (67%). Snowmobile fatalities were associated with use during times of suboptimal lighting (crude odds ratio, 1.9 [95% confidence interval, 1.1-3.3]; P < .01). Blood alcohol concentration exceeded provincial limits in 64% of cases. When snowmobile fatalities were adjusted for occurrence during suboptimal lighting conditions, only alcohol use was associated independently with fatal outcome (adjusted odds ratio, 4.3 [95% confidence interval, 2.5-7.0]; P < .0001). CONCLUSION: Drivers in snowmobile fatalities are associated with an approximately fourfold greater use of alcohol than are age- and sex-matched drivers in automobile and motorcycle fatalities. Preventive strategies should be targeted at reducing the use of alcohol while snowmobile driving in young men.

Accident Prevention↗
PubMed1994

A critical analysis of laparoscopic assisted vaginal hysterectomies compared with vaginal hysterectomies unassisted by laparoscopy and transabdominal hysterectomies.

The first 115 laparoscopically assisted vaginal hysterectomies (LAVH) done by our faculty surgeons were compared with 220 vaginal hysterectomies (VH) and 194 abdominal hysterectomies (AH) done in our affiliated hospitals over the same period of time. Logistic regression analysis indicates that LAVHs were done for cases that would significantly be more likely selected for AH than for VH (p less than 0.0001). Matched case control studies with 28 LAVH/VH and 34 LAVH/AH pairs and bivariate analyses demonstrated that LAVH can be accomplished with low morbidity, short lengths of stay, and little, if any, increase in operating times compared with VH and AH. The LAVH procedure can be expected to replace many AHs in the future.

Adolescent↗
PubMed1994

The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium salt) (Na-PMP) on the taste of bitter-sweet stimuli.

The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium salt) (Na-PMP) on the taste and temporal properties of a range of bitter-sweet stimuli was determined using a trained sensory panel. Na-PMP was found to be an effective inhibitor of the sweetness response of all stimuli tested, reducing both sweetness intensity and persistence. The inhibitor was found to be specific to sweet taste, no reduction in bitterness intensity or persistence was observed at the concentrations of Na-PMP employed in this study. The results therefore do not support the claim of Fuller and Kurtz (1991), that Na-PMP is a potent bitterness inhibitor, but rather support the existence of two distinct receptor sites/loci in sweet and bitter chemoreception.

Adult↗
PubMed1994

A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children: effect of polysaccharide size and linkage characteristics.

Because most childhood invasive pneumococcal disease occurs before the age of 2 years, the development of a pneumococcal vaccine that is immunogenic in infants is a priority. We assessed the safety and serum antibody responses to two dose levels of three bivalent pneumococcal capsular polysaccharide (CPS)-protein conjugate vaccines incorporating the poorly immunogenic serotypes 6A and 23F. The conjugate vaccines differed in CPS size and chemical linkage, but all used a nontoxic cross-reactive mutant diphtheria toxin (CRM197) as the protein carrier. 118 young children 18 to 30 months of age received a single immunization with one of the three glycoconjugates or with licensed pneumococcal vaccine. Sera were obtained before and 1 month after immunization and analyzed by enzyme-linked immunosorbent assay for serotype-specific antibody titers. The 23F CPS was more immunogenic than the 6A CPS in all vaccine formats. The most immunogenic 23F conjugate vaccine consisted of native CPS directly linked to the carrier protein; smaller CPS or the use of a six-carbon linker did not appear to enhance immunogenicity in these young children. Conjugation of two pneumococcal CPSs is associated with an increase in immunogenicity, and the characteristics of the CPS and of the CPS-protein linkage appear to influence the antibody response.

Bacterial Vaccines↗
PubMed1994

Immunogenicity, safety and tolerability of varying doses and regimens of inactivated hepatitis A virus vaccine in Navajo children.

The Navajo are known to be at high risk for hepatitis A virus (HAV) infection. This study investigated the safety and immunogenicity of an investigational, alum-adjuvanted, formalin-inactivated HAV vaccine (VAQTA) developed by Merck Research Laboratories in Navajo children. One hundred two of 212 children, ages 4 to 12 years, were HAV-seronegative (< 10 mIU/ml by an enhanced sensitivity modification of the HAVAB; Abbott). Ninety of these children received the HAV vaccine. Study participants were given vaccines containing various viral protein concentrations: Group A (n = 18), 6 units; Group B (n = 36), 13 units; and Group C (n = 36), 25 units HAV protein (1 unit approximately 1 ng viral protein antigen). Three-dose (0, 8, 24 weeks) and two-dose (0, 24 weeks) regimens were compared in subgroups within B and C. The vaccine was well-tolerated and there were no serious adverse reactions; no vaccinee developed hepatitis A. After 1 dose 82 to 100% of children seroconverted (> or = 10 mIU/ml, modified HAVAB; Abbott) and 100% seroconverted after 2 doses. After 1 dose the geometric mean titer for antibody was: Group A, 22 mIU/ml; Group B, 18 mIU/ml; and Group C, 38 mIU/ml. After 3 doses geometric mean titers increased to 10,106 mIU/ml in Group A, 7258 mIU/ml in Group B and 11,856 mIU/ml in Group C. Further field studies are indicated to evaluate its use in high risk populations, such as the Navajo.

Age Factors↗
PubMed1994

Effects of increasing dietary polyunsaturated fatty acids within the guidelines of the AHA step 1 diet on plasma lipid and lipoprotein levels in normal males.

We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.

Adult↗
PubMed1994

Baseline silent cerebral infarction in the Asymptomatic Carotid Atherosclerosis Study.

BACKGROUND AND PURPOSE: In a group of patients with high-grade asymptomatic carotid artery stenosis, we prospectively determined the prevalence and radiological characteristics of clinically asymptomatic brain infarction evident on computed tomography. Risk factors and extent of carotid disease were also determined. METHODS: Patients randomized into the Asymptomatic Carotid Atherosclerosis Study (ACAS) underwent a neurological history, a detailed stroke/transient ischemic attack questionnaire, and a detailed neurological examination. Computed tomography scans were examined by standardized criteria developed as part of a quality-control program supervised by a neuroradiologist. The presence, location, and size of all cerebral infarctions evident by computed tomography were determined. RESULTS: Among 1132 patients, 848 had no history of stroke or transient ischemic attack. One hundred twenty-six patients (15%) had a silent infarct; 95 (11%) had one, 24 (3%) had two, and 7 (1%) had three or more infarcts. The infarct size was small and deep for 117 patients (72%), less than one-half lobe for 45 (28%), and one-half to less than one lobe for 1 (0.5%). The silent infarcts were evenly distributed ipsilaterally and contralaterally to the study artery but were significantly more frequent in the right hemisphere (P < .05). Factors associated with silent infarction were abnormal gait (P < .001), abnormal deep tendon reflexes or plantar responses (P = .038), but not degree of carotid stenosis. Silent infarction was less frequent among this totally asymptomatic cohort (15%) compared with those with transient ischemic attacks (34/139, 25%; P < .001). CONCLUSIONS: Silent infarction in the setting of asymptomatic carotid stenosis is not uncommon, but silent infarctions are rarely sizable. The clinical significance of silent cerebral infarction in patients with asymptomatic carotid artery stenosis has yet to be established.

Adult↗