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Biomedical subjects

M Borst

Publications and source records attributed to M Borst.

17 recordsLinked to original sources
PubMed1992

Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial.

OBJECTIVE: We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN: A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS: The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION: Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.

Administration, Oral↗
PubMed1991

Surgical evaluation of Henoch-Schönlein purpura. Experience with 110 children.

Henoch-Schönlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schönlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schönlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived.

Abdominal Pain↗
PubMed1991

Transmural gradient of adenosine in canine heart during functional hyperemia.

Effects of beta-adrenergic stimulation and atrial pacing on the transmural gradient of intracellular free adenosine were assessed in dog hearts in vivo by measurement of the accumulation of S-adenosylhomocysteine (SAH) in the presence of homocysteine (1.6 mg.kg-1.min-1 iv). Isoproterenol (0.3-0.5 micrograms.kg-1.min-1 iv for 30 min) consistently enhanced left ventricular dP/dtmax (86%), heart rate (38%), and myocardial oxygen consumption (MVO2; 62%) within 3 min while formation and release of adenosine transiently increased. Diastolic aortic pressure fell from 107 +/- 12 to 58 +/- 5 mmHg, and the transmural gradient of SAH was 1.6-, 2.5-, and 4.4-fold increased in subepi-, mid- myo-, and subendocardial layers, respectively. Adenosine formation was inversely related to diastolic aortic pressure. Maintaining aortic pressure greater than 65 mmHg only slightly enhanced venoarterial difference of adenosine despite a greater augmentation of MVO2. Pacing the heart at 209 +/- 4 beats/min enhanced MVO2 by 42% and increased subepi-, midmyo-, and subendocardial levels of SAH by 1.5-, 3.3- and 1.9-fold, respectively. These results demonstrate that in the in situ heart 1) beta-adrenergic stimulation and pacing cause an inhomogeneous transmural increase in free intracellular adenosine mainly affecting the subendocardial and midmyocardial layers; 2) diastolic aortic pressure as the driving force of coronary perfusion is of critical importance for cardiac adenosine formation; and 3) the kinetics of oxygen consumption and adenosine formation are clearly dissociated during beta-stimulation.

Adenosine↗
PubMed1991

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.

Adolescent↗
PubMed1990

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice. In the latter system PMEA has stronger antiretroviral potency and selectivity than 3'-azido-3'-thymidine (AZT). We have now investigated the effect of the drug in cats infected with the feline immunodeficiency virus (FIV). In vitro, PMEA was found to efficiently block FIV replication in feline thymocytes (50% effective dose, 0.6 microM). When administered to cats at doses of 20, 5, or 2 mg/kg per day, PMEA caused a dose-dependent suppression of FIV replication and virus-specific antibody production. Seropositive field cats with signs of opportunistic infection (gingivitis, stomatitis, and diarrhea) showed clinical improvement during PMEA therapy (5 mg/kg per day) and recurrence of the disease after treatment was discontinued. Thus, FIV infection in cats is an excellent model to test the efficacy of selective anti-human immunodeficiency virus agents in vivo.

Adenine↗
PubMed1990

DNA isolation and Southern analysis: a clinician's view.

DNA isolation and Southern Blot analysis are two of the many techniques currently being used routinely by molecular biologists to discover genetic defects that affect human health. Together these two techniques have greatly aided in the growing knowledge of genetics on a molecular level. Southern blotting can be used to discern genetic deletions, alterations, or amplifications that are not detectable by cytogenetic methods. Several examples of the clinical applications of these methods are discussed in Table 4. Southern analysis has been recently used: (1) to facilitate prenatal diagnosis of sickle cell hemoglobinopathies, (2) to demonstrate human papillomavirus DNA integration in the genome of cervical cancer cells and (3) to demonstrate that oncogene amplification in the tumors of patients with node positive breast cancer correlates inversely with prognosis. Each of these examples not only have diagnostic value for patient care but also may help begin to understand the very basis of the disease processes themselves.

Blotting, Southern↗
PubMed1990

Oncogenes, malignant transformation, and modern medicine.

During the past decade there have been remarkable strides in the understanding of the basic mechanism of cancer. It is now clear that there is a set of genes, known as oncogenes, that can cause cells to become malignant if their expression is altered, either by mutation or overexpression. The products of these genes include growth factors, growth factor receptors, signal tranduction proteins, and DNA binding proteins. The normal cellular counterparts of these genes play very important roles in the regulation of growth and proliferation by normal cells. Another set of genes, anti-oncogenes, also play an important role in preventing abnormal cell proliferation. The remarkable explosion of understanding of the pathophysiology of malignancy has led to a common unifying concept of malignant transformation that applies to all tumors. It is likely that these new insights will lead to improved and more specific treatments for malignant disease in the next decade.

Animals↗
PubMed1989

Glutamate degradation in the ischemic dog heart: contribution to anaerobic energy production.

The present study investigated the conversion of amino acids to succinate and the contribution of this pathway to anaerobic energy production during regional ischemia in the dog heart in situ. The relation between regional myocardial blood flow, estimated by the tracer microsphere technique, and myocardial contents of metabolites (glutamate, alanine, succinate, lactate) as well as their local arterio-venous differences (A-V) were determined. During 30 min of coronary artery occlusion, myocardial glutamate decreased from 2.3 mumol/g wet wt in control tissue to 1.2 mumol/g wet wt in severely ischemic areas, while aspartate was unaffected. Myocardial alanine increased in a 1: 1 stoichiometry compared to glutamate, and succinate accumulated. During control perfusion (118 mmHg), A-V of lactate, succinate and glutamate were +470, -0.7 and -3.9 nmol/ml, respectively. Stepwise reduction of perfusion pressure led to the release of lactate and succinate from the underperfused area; extraction of glutamate occurred at the lowest perfusion pressure investigated (34 mmHg; A-V: -500, -10.4 and +4.2 nmol/ml, respectively). The data indicate that during regional ischemia in vivo, succinate is synthetized exclusively from glutamate via 2-oxo-glutarate, following transamination with glycolytic pyruvate yielding alanine, while the contribution of aspartate is negligible. Using tissue levels of glutamate and lactate together with the local arterio-venous concentration differences of these compounds, it can be estimated that degradation of glutamate delivers 20% of the ATP generated by substrate level phosphorylation reactions. Thus energy production by the glutamate degradation pathway is significant in vivo under conditions of flow deprivation.

Adenosine Triphosphate↗
PubMed1988

Formation of S-adenosylhomocysteine in the heart. I: An index of free intracellular adenosine.

To assess the concentration of free intracellular adenosine in the heart the kinetic properties of cytosolic S-adenosylhomocysteine (SAH) hydrolase were utilized at elevated levels of L-homocysteine (adenosine + L-homocysteine in equilibrium with SAH + H2O). Global hypoxia was induced in the isolated perfused guinea pig heart by graded reduction of perfusion medium PO2 in the presence of saturating concentrations of homocysteine (0.2-1.0 mM). Reduction of PO2 from 660 to 165 mm Hg increased the steady-state concentration of total tissue adenosine from 2.0 +/- 0.2 to 2.8 +/- 0.2 nmoles/g, while the rate of SAH formation increased linearly from 0.22 +/- 0.03 to 2.50 +/- 0.13 nmoles/min/g. When adenosine was exogenously applied at a concentration of 100 microM together with homocysteine (1 mM), SAH accumulation rates were much greater: 23.34 +/- 3.31 and 42.11 +/- 1.73 nmoles/min/g with normoxic (95% O2) and hypoxic (30% O2) perfusion, respectively. The apparent Km and Vmax values for SAH-hydrolase in vivo were estimated to be 20 microM and 59 nmoles/min/g wet wt, respectively. Since the relation between SAH formation and adenosine in the physiological concentration range is linear, the measured rate of SAH accumulation during normoxia and hypoxia permitted the calculation of the free intracellular adenosine level, which was 0.061 nmoles/g (0.08 microM) in the normoxic heart. With hypoxia (PO2 165 mm Hg), this value increased to 1.57 nmoles/g (2.0 microM). Free intracellular adenosine closely correlated with the hypoxia-induced changes in coronary flow. The data reveal that measurement of the rate of SAH accumulation during homocysteine infusion can be used for sensitive assessment of free intracellular adenosine levels. Assuming that the intracellular adenosine concentration equals that in the interstitial space, the results furthermore indicate that the degree of intracellular adenosine formation during hypoxic perfusion is quantitatively sufficient to account for most of the observed increases in coronary flow.

Adenosine↗
PubMed1988

Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion.

Rate of accumulation of myocardial S-adenosylhomocysteine (SAH) was used in an open-chest dog preparation as an index of free cytosolic adenosine levels. Following 30 minutes of coronary artery ligation and infusion of L-homocysteine thiolactone (10 mumol/kg/min i.v.) SAH levels increased from 1.3 (control) to 3.3 nmoles/g in the nonischemic and to values over 100 nmoles/g in the ischemic region. Compared with regional myocardial blood flow the enhanced rate of SAH accumulation was strictly confined to the ischemic area. As long as blood flow was 0.6-1.2 ml/min/g, SAH levels remained unchanged. However, they steeply increased when regional myocardial blood flow decreased below 60% of control. Tissue levels of adenine nucleotides, adenosine, and lactate were not significantly affected in the flow range of 0.4-0.6 ml/min/g but rate of SAH accumulation was enhanced by 400%. In the nonischemic myocardium, SAH accumulation was 60% higher in the subendocardium than in the subepicardium. Decreasing coronary perfusion pressure from 110 to 60, 45, and 35 mm Hg was associated with an exponential increase in coronary venous adenosine release only when perfusion pressure was below 60 mm Hg. Transmural mapping of SAH revealed that at 110 mm Hg SAH was homogeneously distributed, while at a perfusion pressure of 60 mm Hg SAH accumulation was enhanced only in the subendocardial layers. Decreasing perfusion pressure further to 40 and 30 mm Hg not only enhanced subendocardial SAH levels to 120 and 170 nmoles/g, respectively, but also considerably steepened the transmural gradient of SAH. SAH-hydrolase exhibited a broad pH-optimum and its activity in different parts of ventricular myocardium was identical. Our findings provide evidence that 1) measurement of SAH accumulation is a sensitive metabolic index for the assessment of regional myocardial ischemia, 2) significant formation of SAH occurs only when regional myocardial blood flow is less than 0.6 ml/min/g, and 3) transmural SAH gradient, a measure of free cytosolic adenosine, and coronary venous adenosine release significantly increase only when the autoregulatory reserve is exhausted.

Adenosine↗
PubMed1987

Community hospital surgeon-specific infection rates.

A one-year prospective study of surgeon-specific nosocomial infection rates was done in two community hospitals. Hospital A (93 beds) and Hospital B (158 beds) have nearly identical surgical staffs. Unified criteria for the diagnosis of infections, methods of data collection, and coding were used. Data were processed with an IBM 370 computer using Statistical Analysis System (SAS). Each surgeon received semiannual reports of 1) overall infection rate by site, 2) number of surgical wound infections by wound class and type of procedure, 3) pathogens for each deep and incisional infection, and 4) quarterly wound infection rates by wound class. Analysis of reports revealed high Class I surgical wound infection rates for both general and orthopedic surgeons. One person in each group had inordinately high infection rates. These data serve as an objective incentive to reduce surgical wound infections, identify individual problems, and suggest surgical privileges be evaluated by performance.

Cross Infection↗
PubMed1986

Operating room surveillance: a new approach in reducing hip and knee prosthetic wound infections.

A prospective study of surgical wound infections (SWI) in hip prosthesis surgery and total hip and knee replacements at two community hospitals with common surgical staffs was begun in May 1982. The rates of SWI during the first 7 months for four orthopedic surgeons were 9% (3/32) for hip prosthesis surgery and 16.7% (3/18) for total hip and knee replacement, with 12% (6/50) overall. To reduce infections, each orthopedic surgeon agreed to intraoperative surveillance (IOS) of two procedures (hip prosthesis or total hip or knee replacement) by the infection control nurse at each hospital. Significant IOS findings were too many persons in the operating room (five to nine persons), operating room doors opened frequently (25 to 50 times), inconsistent use of prophylactic antibiotics, and excessive conversation. In January 1984, IOS data and recommendations were shared with each orthopedic surgeon, the operating room staff, and the anesthesia personnel. Subsequently, a statistically significant drop in SWI was realized for total hip and knee replacement (1/36 versus 5/36, p = 0.05) and overall (3/73 versus 14/116, p = 0.05). The drop in SWI for hip prosthesis surgery was not statistically significant (2/37 versus 9/80, p greater than 0.10). IOS and individualized communication were effective in reducing SWI.

Aged↗
PubMed1984

Intracellular electrolyte composition in various experimental models of hypertension: an electron microprobe study.

Changes in the intracellular ionic composition in the three models of hypertension studied are not uniform in the cells of the various organs. The composition differs not only from organ to organ, but even among the various cell types within the same organ. Marked differences--even diametrically opposite changes--in the intracellular Na concentration can be detected in the various models of hypertension studied. Hence, one cannot expect to draw a simple unifying hypothesis from an analysis of the changes in intracellular electrolyte concentrations occurring in hypertension. A more quantitative analysis of the intracellular ionic composition in other cells, particularly in vascular cells, is needed to define the characteristics of the various types of hypertension.

Animals↗
PubMedDate not supplied

Folate deficiency and cervical dysplasia.

OBJECTIVE: To test the hypothesis that nutritional deficiency affects the incidence of cervical dysplasia in young women. DESIGN AND SETTING: Case-control study. Participants were derived from community family-planning clinics and referrals to a colposcopy center. PARTICIPANTS: A total of 726 subjects were screened, yielding 294 cases of dysplasia and 170 controls defined by coexistent cytologic and colposcopic evidence. MAIN OUTCOME MEASURES: Planned prior to data collection. Odds ratios were computed using logistic regression models to evaluate association between cervical dysplasia and sociodemographic, sexual, and reproductive factors; smoking; oral contraceptive use; human papillomavirus (HPV) infection; and 12 nutritional indices determined by blind analysis of nonfasting blood specimens. RESULTS: The number of sexual partners, parity, oral contraceptive use, and HPV-16 infection were significantly associated with cervical dysplasia. Plasma nutrient levels were generally not associated with risk. However, red blood cell folate levels at or below 660 nmol/L interacted with HPV-16 infection. The adjusted odds ratio for HPV-16 was 1.1 among women with folate levels above 660 nmol/L but 5.1 (95% confidence interval, 2.3 to 11) among women with lower levels. Interactions of red blood cell folate levels with cigarette smoking and parity were also present but were not statistically significant. CONCLUSION: Low red blood cell folate levels enhance the effect of other risk factors for cervical dysplasia and, in particular, that of HPV-16 infection.

Adolescent↗