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Biomedical subjects

M Newman

Publications and source records attributed to M Newman.

At least 109 records · Page 6Linked to original sources

Chromosome assignment of the murine Hox-4.1 gene.

The murine homebox gene 4.1 was assigned to chromosome 2 by Southern analysis of somatic cell hybrids and by in situ hybridization. This assignment and the report of Featherstone et al. (M. S. Featherstone, A. Baron, S. J. Gaunt, M. G. Mattei, and D. Duboule, 1988, Proc. Natl. Acad. Sci. USA, 85, 4760-4764) indicate that a fourth group of homeobox genes is located on chromosome 2 in the mouse (in addition to the homeobox gene clusters on chromosomes 6, 11, and 15).

Animals↗

A comparison of heat exchangers for blood cardioplegia.

During open heart surgery, myocardial protection provided by oxygenated blood-based cardioplegia is superior to that provided by non-oxygenated crystalloid cardioplegia. However, the widespread use of blood cardioplegia has been limited by the cost and complexity of the associated cooling and delivery systems. The performance of a simple system--a polyethylene coil immersed in ice--has been compared with three systems incorporating specialized, water-jacketed heat exchangers: Buckberg Shiley, Shiley BCD and Bentley HE-100. Blood was diluted to a haematocrit of 22% and delivered to each cooling system at flow rates of 200-500 mL/min and temperatures of 25 degrees C and 30 degrees C. Cooling water at 0-1 degree C was supplied to the heat exchangers at flow rates of 2, 4, and 6 L/min. Performance was measured by comparing the blood outflow temperatures at the same inflow temperature under a variety of test conditions which simulated those occurring in clinical practice. All cooling systems, except the Buckberg Shiley, were able consistently to cool blood cardioplegia adequately (below 10 degrees C), but the ice coil was the most effective. The heat exchanger systems are 3-4 times more expensive than the ice coil and require an external source of cold water. Thus the ice coil system has the advantages of simplicity, efficiency, and economy.

Heart Arrest, Induced↗

The role of liver biopsies in psoriatic patients receiving long-term methotrexate treatment. Improvement in liver abnormalities after cessation of treatment.

Liver biopsy specimens from 168 patients who underwent a total of 364 biopsies were examined. Of 83 patients receiving biopsies before methotrexate treatment, 14 had one or more risk factors predictive of liver abnormality but they had normal pretreatment biopsy specimens. Among 17 patients with abnormal biopsy specimens before methotrexate treatment, only 1 had an identifiable risk factor and 5 had abnormal results of liver function tests. The probability of a normal biopsy specimen after methotrexate treatment dropped below 50% at a cumulative methotrexate dose of 3115 mg for the 31 patients with biopsy specimens from before and after methotrexate treatment and 5776 mg for those who had biopsies only after methotrexate treatment; this difference was statistically significant and is thought to be related to the fact that the patients who had biopsies before and after methotrexate treatment had received most of their medication by the parenteral rather than the oral route. A significant association existed between biopsy grade after methotrexate treatment and obesity. Other risk factors were not correlated with biopsy grade. Blood chemistry tests were not predictive of histopathologic findings. Eight of 11 patients with fibrosis or cirrhosis showed meaningful improvement in liver histologic findings after methotrexate treatment had been withdrawn for 6 months or more; none had progression of abnormalities.

Adolescent↗

A microcomputer-based, net-lending interlibrary loan system.

A microcomputer-based, net-lending interlibrary loan system was developed at Lane Medical Library, Stanford University. The system, designed to generate the monthly billing invoices and all necessary statistical reports, has reduced the time required for logging-in procedures and compilation of monthly, quarterly, and annual statistics. User menus, help screens, and choice fields were developed explicitly for library staff who have little or no computer experience. The program was written using the DataEase database management software running on IBM PC, XT, AT, or compatible with a minimum of 512K RAM. Described are features of this automated interlibrary loan management system and its use in a net-lending interlibrary loan department. It focuses on data entry in the "Library Directory" and "ILL Log Sheet," details of billing invoices, and statistical reports, and flexibility in modifying tax rates, borrowing fees, and other parameters.

Accounting↗

Molecular genetics of the apolipoprotein B gene in pigs in relation to atherosclerosis.

Immunologically defined alleles of the pig apolipoprotein B (ApoB) locus (apoB) are correlated with different blood cholesterol levels and predisposition towards premature coronary heart disease. We show here that these alleles are associated with differences in the apoB gene by identifying six restriction fragment length polymorphisms at the pig apoB locus. We have sequenced a 2.4-kb fragment encompassing exons 11 through 14 of one allele, and 7.1 kb from the 3' one-third of exon 26 to about 1 kb past the last exon from another allele. The decoded amino acids of the pig and human ApoB proteins are identical at 70% of these positions. One region close to the C-terminus of the protein is surprisingly different in pigs and humans (57% identity) but the C-terminal region is relatively well conserved (74% identity). Neither of the two putative low-density lipoprotein (LDL) receptor-binding sites is completely conserved in pigs and humans, but identical stretches of amino acids occur near these sites more frequently than in the other sequenced regions. We compare the nucleotide sequences of the region encompassing the putative LDL receptor-binding sites from four pig alleles, including one implicated directly in atherosclerosis. None of the differences appears to account for the hypercholesterolemic phenotype. We conclude that significant differences in the physiology of LDL particles result from changes outside the putative receptor-binding region.

Alleles↗

The application of immunoassays and fluorometry to the detection of polycyclic hydrocarbon-macromolecular adducts and anti-adduct antibodies in humans.

The metabolic activation of polycyclic aromatic hydrocarbons (PAH) to chemical species that form covalent adducts with cellular macromolecules (DNA and protein) is central to theories of carcinogenesis. Assays are currently being developed that will accurately reflect human macromolecular exposure to these carcinogens. Immunoassays are capable of detecting low levels of PAH-DNA adducts and antibodies directed against these adducts in humans and HPLC/spectrophotofluorimetry allows the detection of carcinogen-DNA or carcinogen-protein adducts in human peripheral blood. Both types of method have inherent advantages and disadvantages, and the use of more than one type of corroborative assay is a feature in our work. Simplified but highly specific synchronous fluorescence spectra have been obtained for BP-tetrols after mild acid hydrolysis and HPLC of sample materials. When using a wavelength difference of 34 nm to drive the excitation and emission monochromators simultaneously, the pyrene fluorophore, when present, has a signature peak at 345 nm (excitation). The results of immunoassays demonstrate human exposure to PAH as a class of carcinogen, since serological cross-reactivity of antibodies does not limit detection in this system to a single chemical compound. In addition the formation in humans of anti-PAH-DNA antibodies has been shown, presumably in response to both past and present exposure to the parent compounds. In summary the results of each assay can indicate human exposure to PAH and have the potential for molecular dosimetry of this exposure.

Antibodies↗

Internal cardiac cooling improves atrial preservation: electrophysiological and biochemical assessment.

This study was designed to determine if the improved hypothermia that can be achieved with cold perfusion of the right atrium is associated with improved atrial preservation. During 120 minutes of cardioplegic arrest, 7 dogs with occlusive caval cannulation underwent right atrial (RA) perfusion with cold blood and 7 dogs with a single atriocaval cannula served as controls. RA perfusion produced a lower atrial septal temperature than atriocaval cannulation, 96% less electrical activity during arrest, and a lesser prolongation of the A-H interval after reperfusion (40% versus 123%; p less than 0.01). At the end of arrest, compared with atriocaval cannulation, RA perfusion was associated with improved preservation of creatine phosphate (71 +/- 10% versus 40 +/- 7% of control; p less than 0.05) and a lower level of lactate in the RA wall (8 +/- 1 mumol/gm versus 15 +/- 2 mumol/gm; p less than 0.01). We conclude that improved hypothermia reduces electrical activity and anaerobic metabolism in the atrial myocardium during cardioplegic arrest and improves atrioventricular conduction following arrest.

Adenosine Triphosphate↗

Detrusor instability following colposuspension for urinary stress incontinence.

Sixty-two patients with genuine stress incontinence (group A) and 30 women with combined detrusor instability and genuine stress incontinence (group B) had a colposuspension operation. The proportion with symptoms of detrusor instability was significantly reduced from 24% before operation to 9% after operation in group A and from 73% to 33% in group B. Urodynamically, detrusor instability developed after surgery in 17 of the 62 patients (27%) in group A whereas only 12 of the 30 women (40%) in group B had detrusor instability after surgery. No urodynamic explanation was found to explain the effect of colposuspension in relieving the symptoms of detrusor instability in some and causing them in others. Nevertheless, it is suggested that colposuspension is helpful for most patients with combined detrusor instability and genuine stress incontinence.

Adult↗

Supernumerary nipples.

Supernumerary nipples are common anomalies, and their significance is usually limited to cosmetic concerns. However, a high index of suspicion should be maintained during physical examinations, because any disease process that involves anatomically normal breasts may affect aberrantly located breasts or nipples as well. These anomalies may be associated with several systemic disorders, particularly urinary tract abnormalities.

Abnormalities, Multiple↗

HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis.

Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen-committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B-lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24 gag protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, kappa) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I-infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis.

Antibodies, Viral↗

Coronary blood flow and myocardial metabolism during reperfusion after hypothermic cardioplegia in the dog.

There have been many studies of reperfusion injury after normothermic ischemia. However, there have been few clinically relevant studies on the nature and time course of recovery of the myocardium during reperfusion after hypothermic cardioplegia. We studied reperfusion in the isolated dog heart supported by another dog. After 2 h of cardioplegic arrest at 20 degrees C, 11 normal hearts were reperfused for 30 min at optimal coronary pressures (60-100 mm Hg mean). The following events occurred: rapid rewarming, a transient hyperemia followed by a rapid return of both coronary blood flow and myocardial oxygen consumption to normal, washout of lactate, recovery of contractility and a slight decline in ATP. Most of these events occurred during the first 15 min of reperfusion. We concluded that, in normal hearts which are well protected during hypothermic cardioplegia, reperfusion at optimal coronary pressure results in recovery of the myocardium within 15 min, with the exception of recovery of ATP levels.

Animals↗

Trial of 17-hydroxyprogesterone caproate (Proluton Depot) in women with long-standing infertility; failure of estrogen positive feedback the following cycle.

In open and double-blind studies 40 women with long-standing unexplained infertility were investigated and treated with 17 alpha-hydroxyprogesterone caproate (17HPC, Proluton Depot). In the open study, 16 women with a high index of suspicious abortions were given 500 mg 17HPC imtramuscularly (i.m.) weekly for 6-16 weeks. Six of the women received the drug from a time preceding the expected date of a period; 2 of these conceived that cycle and their pregnancies continued to term, while 4 were not pregnant. Ten women (9 with definite previous abortions) were given 17HPC when they suspected (correctly) that they were pregnant. Their pregnancies continued to term in all but 1, who had a premature delivery (still-birth) at 34 weeks. In the double-blind study 24 women were given injections of 17HPC or placebo i.m. at weekly intervals, from about 4 days before the expected period (day -4), provided that the level of progesterone (Prog) (on days -9 to -7) was greater than 10 nmol/l. After placebo no delay in menstruation or disruption of the succeeding cycle was observed. In 14 of 16 cycles in 14 women given 500 mg 17HPC the withdrawal period was delayed by a few days, and then followed by highly erratic bleeding over the next 1-3 months. The dose was therefore reduced to 250 mg 17HPC but the same problem resulted in 8 of 29 cycles in 16 women (including the above studied in later cycles). Regular cycles were eventually restored in all cases but in 3 this necessitated treatment with the contraceptive pill (Microgynon). In most of the post-treatment cycles there was a progressive and prolonged estradiol (E2) rise, which was not preceded by changes either in serum FSH concentration or in the LH/FSH ratio nor associated with the expected positive feedback rise in LH. We conclude that 17HPC disrupts the following cycle, probably by allowing follicular development while interfering with positive LH feedback. None of the patients of the double-blind study had conceived (as evidenced by undetectable hCG levels). Our study confirmed that this progestogen exerts no direct luteolytic effect. However, in order to establish the efficacy or otherwise of 17HPC given before the end of the cycle, women should be selected with a very high index of suspicion of recurrent early implantation failure or abortion.

17 alpha-Hydroxyprogesterone Caproate↗

Predictive value of stool examination in acute diarrhea.

We prospectively evaluate the value of fecal blood and fecal leukocytes in predicting whether acute diarrhea in adults is associated with a stool culture positive for a bacterial pathogen. One hundred thirteen patients, aged 19 to 50 years, seen in a two-year period in an urban adult outpatient setting underwent stool culture for the presenting symptom of diarrhea. Heterosexual men represented 48% of the cohort, women represented 17%, and homosexual men represented 35%. Overall, 53 (47%) of the patients had positive stool cultures for enteric pathogens. Campylobacter jejuni was the most common organism in the entire cohort, but Shigella species were most common in homosexual men. The best predictive variables for a stool culture positive for a bacterial pathogen were the presence of both fecal leukocytes and fecal blood in the stool, compared with only one or neither. When both were present, the sensitivity was 81%, the specificity 74%, and the predictive values of a positive and negative test were 81% and 83%, respectively; the likelihood ratio was 4.87. When homosexual men and the rest of the cohort were analyzed separately, the combination of fecal leukocytes and fecal blood remained the best method of predicting a positive stool culture in both. Examination of stool for fecal leukocytes and fecal blood is a rapid, reliable, and inexpensive way to differentiate between bacterial and other causes of acute diarrhea in the adult acute care setting.

Adult↗