We investigated the intramucosal nerve cells of the human small intestine with histochemical methods to demonstrate nicotinamide adenine dinucleotide diaphorase and acetylcholinesterase and with morphometry. Intramucosal neurons appeared as solitary cells or in small groups, especially in the ileum. Most intramucosal nerve cell bodies were round or oval; some were flat or spindle-shaped. They mostly lay close to the muscularis mucosae, but some were located within the muscularis mucosae and others were some distance away from it. The processes of some mucosal neurons projected towards the submucosa. Most mucosal nerve cells showed acetylcholinesterase activity. The frequency distribution of nerve cell profile areas in the intramucosal cells in the duodenum differed from that of cells in the ileum (P < 0.001). There were more large mucosal nerve cells in the mucosa of the duodenum than in the ileum. There was no significant difference between the frequency distributions of cell profile areas of cells of the mucosa and cells of Meissner's and Henle's plexuses in the same region. We conclude that intramucosal nerve cells, similar to those of the submucosal plexus, exist in the human small intestine. The size of intramucosal nerve cell profiles differs between the duodenum and ileum. This is consistent with their possible different functions.

Acetylcholinesterase↗

PubMedDate not supplied

Synthesis of human insulin gene. VIII. Construction of expression vectors for fused proinsulin production in Escherichia coli.

We have constructed two families of plasmids suitable for the cloning of genes and for directing the synthesis of large amounts of fused proteins in Escherichia coli. The plasmids include the E. coli lac promoter and a portion of the coding sequence for beta-galactosidase, which can code for approx. 590 or 450 amino acids. The truncated beta-galactosidase gene ends with a poly-linker region at the 3' end, which can be cleaved by any one of the eight common restriction enzymes and joined to the gene coding for any desired protein. Each family includes three plasmids that enable fusion to be made in all three of the translational reading frames. We have cloned a synthetic human proinsulin gene into these plasmids, and 30% of the total E. coli protein was represented by the 590 amino acid-long truncated beta-galactosidase fused to proinsulin. The yield of proinsulin in this system is more than twice the amount produced by using a 1007 amino acid-long beta-galactosidase gene for fusion.

Base Sequence↗

PubMedDate not supplied

Electrical and structural remodeling of the failing ventricle.

Heart failure (HF) is a complex disease that presents a major public health challenge to Western society. The prevalence of HF increases with age in the elderly population, and the societal disease burden will increase with prolongation of life expectancy. HF is initially characterized by an adaptive increase of neurohumoral activation to compensate for reduction of cardiac output. This leads to a combination of neurohumoral activation and mechanical stress in the failing heart that trigger a cascade of maladaptive electrical and structural events that impair both the systolic and diastolic function of the heart.

Arrhythmias, Cardiac↗

PubMedDate not supplied

Replacement of serum in cell culture by hormones: a study of hormonal regulation of cell growth and specific gene expression.

The hypothesis that the growth of mammalian cells is regulated by hormones is now supported by considerable evidence. Two rat pituitary cell lines, GH3 and GC, a mouse melanoma, M2R (B16), and a human cervical carcinoma cell, HeLa S-3, have been grown indefinitely in serum-free (SF) hormone-supplemented medium. No visible changes of growth characteristics were observed in the cells grown continuously in the SF condition. However, changes in the activity of a plasma membrane enzyme, alkaline phosphatase, and in the relative intensity of surface proteins that are labeled by the [125I] lactoperoxidase technique were found in HeLa cells grown in the SF condition. To study the role of hormones required in the regulation of cell growth, HeLa cells were grown in the absence of one of the required hormones. The following results were obtained. Epidermal growth factor is probably involved in the regulation of the synthesis of macromolecules such as RNA and of the protein content per cell. Transferrin, the accessory factor in the SF condition, supplies iron for cells. The two basic peptides in this SF system, fibroblast growth factor and insulin, are probably involved in the balance of nutrients and energy inside the cell. The replacement of F12 medium with a better-balanced medium, MCDB 105, can mimic the requirements for these two peptides. The steroid hydrocortisone (HC) is probably involved in alteration of the cell surface. This is indicated by the effects of HC on cell morphology, rate of detachment from the dish, and the pattern of [125I] lactoperoxidase labeling of surface proteins. In addition, it is necessary to change the medium more frequently to maintain the culture in the medium without HC. This observation suggests that HC may be involved in the control of homeostatic properties of the cell surface. The production of rat prolactin by GH3 cells was also studied. GH3 cells in the SF condition produce 1.6 microgram prolactin per 10(5) cells in 24 h, while 2.4 microgram is produced in the presence of serum. Prolactin production in the SF condition is enhanced by the presence of thyrotropin-releasing hormone and inhibited by triiodothyronine (T3). T3 is the major growth factor for these cells. Without it cell growth is severely limited, while prolactin production is elevated. This result suggests that the GH3 cell line in the SF condition may be an ideal system for the study of hormonal regulation of cell growth and specific gene expression.

Alkaline Phosphatase↗

PubMedDate not supplied

Evaluation of the online immunoassay for propoxyphene: comparison to EMIT II and GC-MS.

A study was conducted to compare the clinical sensitivity of the OnLine and EMIT II assays for propoxyphene (PPX) use in human urine. A total of 5138 random clinical samples were evaluated by both OnLine and EMIT II. Samples that were positive for each immunoassay were confirmed for PPX and norpropoxyphene (NPPX) by gas chromatography-mass spectrometry (GC-MS). There were 14 samples that were identified positive by both immunoassays and confirmed positive by GC-MS. An additional six samples were positive by OnLine, negative by EMIT II, and confirmed positive by GC-MS. There was one unconfirmed positive sample identified by each immunoassay, and 5116 samples were identified as negative by both immunoassays. The increased sensitivity by OnLine can be attributed to the cross reactivity of the OnLine antibody, which is higher than the cross reactivity of the EMIT II antibody for NPPX (77% versus 7%, respectively). The high concentrations of NPPX, relative to those of PPX, found in all of the clinical samples suggest that laboratories that currently confirm for PPX should confirm for NPPX in order to obtain a better correlation between immunoassay results and GC-MS confirmations.

Analgesics, Opioid↗

PubMedDate not supplied

Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree.

An outcrossed canine pedigree was developed for quantitative trait locus (QTL) mapping of hip dysplasia by breeding dysplastic Labrador retrievers to trait-free greyhounds. Measured susceptibility traits included age at onset of femoral capital chondroepiphyseal ossification (OSS), maximum hip distraction (laxity) index (DI), and the dorsolateral subluxation (DLS) score. The pedigrees consisted of 147 dogs representing four generations. For 59 dogs genotyped with 65 microsatellites, the median heterozygosity and polymorphic information content (PIC) values of the F(1) generation were 0.82 and 0.68, respectively. Seventy-seven percent of microsatellites had a PIC greater than 0.59 in the F(1)s. Ninety-six percent of alleles showed Mendelian inheritance. Based on marker informativeness, approximately 350 randomly selected markers would be required for genome-wide screening to obtain an average interval between informative markers of 10 cM. Heritability was estimated as 0.43, 0.5, and 0.61 for OSS, DI, and the DLS score, respectively. Biometric estimates of the mean (+/- variance) effective number of segregating QTLs was 1.2 (+/- 0.05), 0.8 (+/- 0.02), and 1.0 (+/- 0.03) for OSS, DI, and the DLS score, respectively. The distributions of simulated backcross trait data suggested that the loci controlling these traits acted additively and that the DI may be controlled by a major locus. When combined with previous power and quantitative genetic analyses, these estimates indicate that this pedigree is informative for QTL mapping of hip dysplasia traits.

Animals↗

PubMedDate not supplied

Carotid bifurcation CT angiography: assessment of interactive volume rendering.

PURPOSE: The purpose of this study was to compare the accuracy of CT angiography (CTA) for the assessment of carotid bifurcation stenosis, using interactive volume rendering (VR), maximum intensity projection (MIP), and 2D transverse CT technique (t-CT). METHOD: Nineteen consecutive patients were prospectively studied with CTA and selective digital subtraction angiography (DSA). There were 13 men and 6 women from 51 to 84 years old (mean 70 years). Results of DSA were compared with those of interactive VR, MIP, and conventional t-CT results, using North American Symptomatic Carotid Endarterectomy Trial criteria for stenosis grading. RESULTS: There were a total of 38 carotid bifurcations studied, with 9 mild, 10 moderate, and 15 severe stenoses and 4 occlusions. Overall agreement with DSA for VR was achieved in 76%. Eighty percent of the severe stenoses were correctly predicted by VR. The overall agreement between t-CT and DSA was 89%. MIP images, when analyzed independently, showed an overall agreement with angiography of only 71%. VR was not significantly different from MIP (p = 0.60). The difference between VR and t-CT had borderline significance (p = 0.09). MIP had significantly poorer agreement with angiography than t-CT (p = 0.02). CONCLUSION: CTA has a high degree of accuracy for the assessment of carotid artery disease compared with catheter angiography. Interactive VR increases the accuracy of diagnosing carotid stenosis and decreases the number of unsatisfactory studies as compared with MIP. Further advances in computation speeds and improvements in software may dramatically alter the future use of VR for the communication of results to clinicians; however, careful analysis of transverse sections is essential to accurate CT interpretation.

Aged↗

PubMedDate not supplied

Hypopituitarism and chorioretinopathy in two siblings.

Two male siblings with chorioretinopathy and pituitary dysfunction (CPD) were found to have empty sellas on CT scan. Extensive ophthalmological and endocrinological investigation revealed the absence of gonadotrophins in both brothers and growth hormone deficiency in one. ACTH, TSH, and posterior pituitary function were normal. Karyotyping in one brother revealed a 46XY complement. Ophthalmological evaluation of three other siblings and both parents revealed normal vision and no evidence of retinopathy. The brothers represent two additional examples of CPD syndrome, suggesting a genetic etiology for this syndrome complex. The empty sellas present add another facet to the central nervous system disorders found in CPD syndrome.

Adolescent↗

PubMedDate not supplied

Twenty-four-hour cortisol profiles demonstrate exaggerated nocturnal rise in diabetic children.

Plasma cortisol was measured every 20 min for 24 h in 12 normal and 8 insulin-dependent, nonketotic, diabetic children treated with one daily injection of insulin. Plasma glucose was also measured every 20 min in the diabetic children. The diurnal pattern of cortisol secretion was identical. The mean 24-h plasma cortisol was similar in both groups, but significantly elevated in the diabetic children between 0200 and 0920 h. Peak cortisol levels were higher in the diabetic than in the normal children. No correlation was found between average plasma glucose and average plasma cortisol, or between the nocturnal change in plasma glucose and average nocturnal plasma cortisol in the diabetic subjects. These studies demonstrate an exaggeration of the normal nocturnal rise in plasma cortisol in diabetic children not related to the levels of plasma glucose.

Adolescent↗

PubMedDate not supplied

Differences in the obstetric malpractice claims filed by Medicaid and non-Medicaid patients.

BACKGROUND: Many physicians believe Medicaid patients are more likely than non-Medicaid patients to file malpractice claims. This study examines the accuracy of this belief in regard to obstetric malpractice claims. METHODS: Claims filed between January 1982 and June 1988 from the major malpractice insurer in Washington State were used to compare obstetric malpractice claims filed on behalf of Medicaid and non-Medicaid patients. RESULTS: Eleven percent (7/62) of all closed obstetric claims were filed by Medicaid patients, whereas 19 percent of all births in Washington State were to Medicaid patients between 1982 and 1988. Failure to diagnose or treat a fetal condition was the most commonly alleged negligence in both Medicaid and non-Medicaid groups. Most claims in both groups were settled before the cases went to court; a substantial minority of claims were dropped. The mean cost of Medicaid claims ($406,984) was three times that of non-Medicaid claims ($133,743), suggesting that paid Medicaid claims were more severe than paid non-Medicaid claims. CONCLUSIONS: Medicaid patients appear no more likely to file obstetric malpractice claims than non-Medicaid patients. The low likelihood of filing claims, coupled with large settlements, suggests that Medicaid patients may have less access to legal services than non-Medicaid patients.

Female↗

PubMedDate not supplied

Can physicians be induced to resume obstetric practice?

BACKGROUND: Decreased numbers of obstetric providers during the last decade have limited access to obstetrics care, especially for some groups of women. Increasing or stabilizing the number of providers could increase access. METHODS: A questionnaire was mailed in 1989 to 1965 Washington State family physicians and obstetricians to determine their attitudes toward the practice of obstetrics. Sixty-six percent of physicians responded to the survey. RESULTS: Of those who had quit obstetrics in the previous 3 years, 42 percent of responding family physicians and 19 percent of responding obstetricians would consider resuming. Those family physicians willing to consider resuming their obstetric practices were more likely to have been in practice fewer years, employed by a health maintenance organization (HMO), or located in a rural area. A majority of all respondents cited excessive malpractice premiums and fear of malpractice suit as reasons for stopping obstetric practice. Family physicians willing to consider resuming obstetrics were more concerned about the overall number of obstetric providers in their area. Rural family physicians willing to consider resuming obstetrics listed poor backup or shared call more often as a reason they had quit. CONCLUSIONS: Attention targeted to the concerns of family physicians who have been in practice for a short time, who work for HMOs, or who are in rural practice might help induce some physicians to resume obstetrics.

Attitude of Health Personnel↗

PubMedDate not supplied

Prolonged PR interval is a risk factor for bradycardia during spinal anesthesia.

BACKGROUND AND OBJECTIVES: Bradycardia occurs during 9%-13% of spinal anesthetics and may lead to cardiac arrest. Several risk factors for the development of bradycardia have been identified, but the risk conferred by presence of abnormalities detected on preoperative electrocardiogram (ECG) has not been examined. The authors undertook the study to correlate abnormal ECG findings with the incidence of bradycardia. METHODS: The data-base was previously collected from 952 patients undergoing spinal anesthesia. Patient records were reviewed and 537 had ECGs performed within 6 months of surgery. Intraoperative bradycardia was defined as a heart rate < 50 bpm (plus > 10% decrease from baseline). Abnormalities recorded from the ECG were prolonged PR interval (PR > 0.2 sec), atrial-ventricular conduction abnormalities, evidence of chamber hypertrophy, ischemia, and infarction. The findings were compared with incidence of bradycardia using contingency tables. Significant correlations were then evaluated with logistic regression. Significance was defined as P < .05. RESULTS: The incidence of bradycardia in this population was 12%. Patients with a prolonged PR interval had an increased incidence of bradycardia (25%, P = .01). Other ECG abnormalities did not correlate with increased incidence of bradycardia. Duration of PR interval did correlate significantly (P = .001) but poorly (r2 = 0.014) with baseline heart rate. However, logistic regression demonstrated that prolonged PR interval was a significant and independent predictor for bradycardia (odds ratio = 3.2, P = .01). CONCLUSIONS: Risk factors previously identified for the development of bradycardia during spinal anesthesia include: baseline heart rate < 60 bpm, ASA physical status 1 versus 3 or 4, use of beta-blocking drugs, sensory block height > or = T5, and age < 50. The results demonstrate that prolonged PR interval on the preoperative ECG is another significant and independent predictor for bradycardia.

Adult↗

PubMedDate not supplied

Detection of mutagens in cervical mucus in smokers and nonsmokers.

The Salmonella mutagenicity test was used to analyze cervical mucus specimens from 364 smokers and 333 nonsmokers to determine whether the association between smoking and mutagenic cervical mucus that we reported previously among women diagnosed with dysplasia would apply to a larger group of healthy women (E. A. Holly et al., J. Natl. Cancer Inst., 76: 983-986, 1986). Women smokers and nonsmokers between the ages of 18 and 49 who attended eleven clinics and physicians' offices in the San Francisco Bay area for a routine Pap smear were examined to determine whether smokers were more likely to have mutagenic substances in their cervical mucus. About 4% of smokers and 8% of nonsmokers had positive mutagenicity test results (P = 0.02). Cervical mucus with a large number of microorganisms was more likely to have a positive mutagenicity test result than that with fewer microorganisms (test for trend, P = 0.01). Mutagenicity results varied by race and clinic location but were not associated with smoking behavior, sexual behavior, gynecological diagnosis, or diet. Further work is needed to develop methods to detect mutagens in specific body fluids.

Adolescent↗