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Biomedical subjects

J Lynch

Publications and source records attributed to J Lynch.

At least 217 records · Page 12Linked to original sources

Role of insulin-like growth factor-related peptides in the estradiol-, prolactin-, and progesterone-stimulated growth of N-nitrosomethylurea-induced rat mammary tumors in soft agar.

The present experiments were designed to test the role of insulin-like growth factor-related peptides (IGF-RPs) in hormonally stimulated N-nitrosomethylurea (NMU)-induced mammary tumor colony formation in soft agar. To evaluate production of IGF-RP by NMU cells, we tested the abilities of a monoclonal antibody directed against insulin-like growth factor I (alpha sm 1.20B) and of a polyclonal antibody raised against the insulin-like growth factor I (Ab 134) to inhibit the colony-stimulating effects of conditioned media (CM) obtained from estradiol (E2)-, prolactin (PRL)-, and progesterone (Pg)-treated NMU-induced rat mammary tumors. Both Abs abolished the colony-stimulating action of genuine insulin-like growth factor I while having no effect when added alone or with control CM. The addition of either alpha sm 1.20B or Ab 134 (but not that of an irrelevant Ab) consistently blocked the colony-stimulating action of E2-CM, PRL-CM, and Pg-CM, suggesting that IGF-RPs are produced by NMU mammary tumor cells exposed to these hormones. Next, we directly tested the role of IGF-RPs as mediators of hormonally stimulated growth. We indeed observed that the addition of alpha sm 1.20B markedly inhibited the colony-stimulating actions of E2, PRL, and Pg added to NMU mammary tumor cells in soft agar in the absence of serum. We conclude that, in our experimental system, IGF-RPs not only are produced upon exposure to E2, PRL, and Pg, but also are important mediators of hormonally stimulated growth.

Animals↗

Prenatal diagnosis and linkage disequilibrium with cystic fibrosis for markers surrounding D7S8.

Three polymorphic DNA markers surrounding the D7S8 locus were tested for their usefulness in the diagnosis of cystic fibrosis (CF) by linkage analysis. The markers correspond to the loci D7S424 and D7S426. These polymorphisms were studied by centers in the U.S., the United Kingdom, the Netherlands, and Italy, using samples from populations throughout Europe and North America. The additional information provided by these probes increased the heterogeneity of the region from 50% to 58% and was essential for a completely informative diagnosis in one family. A very high degree of linkage disequilibrium was found between these markers, which span a distance of approximately 250 kb. In addition, linkage disequilibrium with CF was noted. Significant heterogeneity of linkage disequilibrium was found among the populations, both for the marker-marker pairs and between the markers and CF.

Cystic Fibrosis↗

Comparison of a modified Fick method with thermodilution for determining cardiac output in critically ill patients on mechanical ventilation.

We compared a modified Fick method for measuring cardiac output against the thermodilution method in 11 critically-ill patients on mechanical ventilation. Oxygen consumption (VO2) was calculated indirectly, by measuring the carbon dioxide elimination (VCO2) during steady state and by assuming an average respiratory quotient of 0.9. For a total of 129 measurements, the mean difference in cardiac output between both methods was 0.03 +/- 1.3 l/min (95% confidence interval, -0.19 to 0.25 l/min, p = 0.7) standard deviation, with the largest differences being measured in the low cardiac output range (less than 5 l/min). No statistically significant difference was found between the cardiac output values obtained with either method. These data showed a good correlation between the two methods and suggest that the modified Fick method may be useful in determining cardiac output in seriously ill patients on mechanical ventilation not requiring pulmonary arterial catheterisation, or where facilities for undertaking metabolic measurements are not available.

Adult↗

Hereditary carcinoma of the ovary and associated cancers: a study of two families.

Increasing attention has been given to host factors in the etiology of ovarian carcinoma. Case/control studies have shown a significant excess of this disease among primary relatives of ovarian cancer affected. Pedigree studies have demonstrated its occurrence on a site-specific basis, in association with carcinoma of the breast (breast/ovarian carcinoma syndrome), and in other hereditary disorders. The complexity of this heterogeneity clearly warrants more intensive family studies. We have described genetic and clinicopathologic nuances in two extended ovarian cancer-prone families. The absence of premonitory physical stigmata and/or biomarkers which signify the cancer-prone genotype compels the physician to employ the best posits from the pedigree to identify those patients who are at inordinately high risk for ovarian and/or syndrome-associated cancer so that surveillance strategies can be more focused. Because of limitations of current surveillance strategies for the early detection of ovarian carcinoma, the clinician's responsibility includes the identification and counseling of candidates for prophylactic oophorectomy.

Adult↗

Spondylitis without epidural abscess formation following short-term use of an epidural catheter.

A 42-year-old patient had undergone total hip replacement for aseptic femoral head necrosis 9 years previously. He now presented with loosening of the prosthesis and pseudoarthrosis sustained following a femoral shaft fracture 7 months earlier. A total hip replacement was carried out in general anaesthesia combined with an epidural catheter. The epidural catheter was removed on the third postoperative day, after which the patient complained of persistent lumbar pain which was associated with meningismus, fever, leucocytosis and a raised erythrocyte sedimentation rate. In spite of intensive laboratory and radiological investigation, 15 weeks elapsed before a radiological diagnosis of spondylitis of L1 and L2 could be made. Aspiration biopsy of the L1/L2 disc space yielded a growth of Pseudomonas aeruginosa. Antibiotic therapy was begun immediately but could not prevent spread of infection to the adjacent disc-space T12/L1 and the vertebral body T12. The patient made a slow recovery and was discharged in a satisfactory condition wearing a lumbar brace some 9 months after the operation. No evidence of epidural abscess formation was found at any stage and no direct connection between the use of the epidural catheter and spondylitis could be established.

Abscess↗

Consumer evaluation of the quality of hospital services from an economics of information perspective.

Consumer evaluations of the quality of hospital services have become increasingly important as the patient and the patient's family have become more involved in hospital selection. The authors investigate the appropriateness of the search, experience, and credence typology of economics of information theory as a framework for analyzing how consumers judge the quality of specific hospital services. Advertising strategies are recommended for each category for hospitals seeking to create images of quality and excellence.

Advertising↗

Exposure to a chloride-deficient formula during infancy: outcome at ages 9 and 10 years.

A school-based survey of the 1978 to 1979 birth cohort of two metropolitan Washington, DC, counties was conducted to find children who had been exposed to the chloride-deficient formulas Neo-Mull-Soy and Cho-Free during infancy. Children who had ingested other soy formulas that had an adequate chloride content were also found and matched to the exposed children by sex, race, birth weight, the age of the child, the mixed feeding status of the child, and maternal education. One hundred seventy-one of the exposed children and 261 soy control children were given a battery of psychologic tests in their homes to determine whether there had been any effect on intellectual development as a result of exposure to the chloride-deficient formulas. There were no differences in scores between the groups on the Wechsler Intelligence Scale for Children-Revised, the Boston Naming Test, the Rey-Osterrieth Test, or the FAS Verbal Fluency Test. There was no correlation between duration of exclusive exposure to the chloride-deficient formulas and the Wechsler Intelligence Scale for Children-Revised Full-Scale IQ Score (Pearson product-moment r = -.0825, P = .28). These results cannot be extrapolated to exposed children with documented hypochloremic metabolic alkalosis. It is concluded that in children without documented evidence of hypochloremic metabolic alkalosis, exposure to the chloride-deficient formulas Neo-Mull-Soy or Cho-Free during infancy has not resulted in any long-term adverse effects on cognitive development.

Child↗

Cholera in Louisiana. Widening spectrum of seafood vehicles.

The largest cholera outbreak in the United States in over a century occurred in Louisiana from August through October 1986. Eighteen persons in 12 family clusters had stool culture or serologic evidence of infection with toxigenic Vibrio cholerae 0-group 1. Thirteen of these persons had severe diarrhea, and 4 required intensive care unit treatment. Although all 18 survived, 1 96-year-old woman with suspected cholera died shortly after hospital admission. A case-control study showed that case-patients were more likely than neighborhood control subjects to have eaten cooked crabs or cooked or raw shrimp during the week before illness. Case-patients who ate crabs were more likely than control subjects who ate crabs to have undercooked and mishandled the crabs after cooking. A third vehicle from the Gulf waters, raw oysters, caused V cholerae 01 infection in two persons residing in Florida and Georgia. All three seafood vehicles came from multiple sources. Stool isolates from the Louisiana case-patients were genetically identical to other North American strains isolated since 1973, but differ from African and Asian isolates. While crabs are the most important vehicle for V cholerae 01 infection in the United States, shrimp and oysters from the Gulf coast can also be vehicles of transmission. A persisting reservoir of V cholerae 01 along the Gulf coast may continue to cause sporadic cases and outbreaks of cholera in Gulf states and in states importing Gulf seafood.

Adult↗

Hormonal control of polyamine pools in experimental breast cancer in vivo: correlation with estrogen and progesterone receptor levels.

The present experiments were designed to test whether, in the hormone responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor, polyamine levels are under hormonal control and whether they correlate with estrogen (ER) and progesterone (PgR) receptor content. We observed that tumor regression induced by ovariectomy was associated with a decline in putrescine (Pu), spermidine (Sd) and spermine (Sm). Administration of estradiol and perphenazine (to stimulate endogenous prolactin release) to castrated rats restored tumor growth and contents of Pu and Sd to control values in a time dependent fashion while Sm levels were only modestly raised. The hormonal modulation of tumor polyamine levels was particularly obvious when the treatment effects on total pools (i.e. Pu + Sd + Sm) were analyzed. No significant correlation was observed between ER and PgR and polyamines in the tumors of intact rats as well as most of the treated groups. In contrast, a highly significant correlation was observed between ER and PgR levels. We conclude that in this experimental system cellular polyamine levels are hormonally regulated but are not correlated with the ER and PgR content of the tumor.

Animals↗

Tracheal agenesis: a case report.

Tracheal agenesis is described in a premature infant. Absent cry, failure of tracheal intubation despite adequate ventilation with a face mask, and ventilation of both lungs after oesophageal intubation suggested the diagnosis. The infant's condition deteriorated rapidly because of severe pulmonary hyaline membrane disease 12 h later due to intractable cardiac failure. At post-mortem examination, large bilateral broncho-oesophageal fistulae were found.

Congenital Abnormalities↗

Genetic and immunopathological findings in a lymphoma family.

We have studied a remarkable family with seven cases of malignant lymphoma extending through three generations wherein five sisters and their mother had histopathologically documented non-Hodgkin's lymphoma, while a granddaughter had Hodgkin's disease. An immunological study of three lymphoma survivors, nine of their first degree relatives, and four spouse controls was undertaken. Significant findings consisted of a depressed serum IgG3 level in four of the nine first-degree relatives; in two of these four, lymphocyte stimulation by both pokeweed mitogen and concanavalin A were significantly depressed. The subtle immunological abnormalities present in this kindred may be associated with the pathogenesis of the lymphomas.

Adult↗

Salinity stress increases cytoplasmic ca activity in maize root protoplasts.

High concentrations of NaCl immediately elevated cytoplasmic Ca activity in maize (Zea Mays L. cv Pioneer 3377) root protoplasts, as measured with the fluorescent probe Indo-1. The effect of salinity was inhibited by Li pretreatment but restored by inositol, suggesting that phosphoinositides mediate the stress response.

Journal Article↗

Parasitic conjoined twins with omphalocele and tetralogy of Fallot.

Human parasitic twins are very rare. Here we report a unique case of a partial twin attached to the host in the midline at the forehead, chin, chest, and epigastrium. The parasite lacked thoracic organs and major neural tube derivatives. However, it had small peripheral nerves and ganglia within perirenal and pericolonic connective tissue. Also present were a well-developed small intestine, colon, and appendix with normal submucosal and myenteric plexuses. These findings may represent either the initial presence of a neural tube that later regressed or migration of autosite neural crest cells. The parasite had a mature, functioning kidney with its ureter opening to skin and complete absence of urinary bladder or genital organs. This raises questions about the embryological development of the ureteric bud, which is an outgrowth of the mesonephric duct. The host had tetralogy of Fallot and omphalocele containing the parasitic kidney and bowel. Parasitic twinning occurs at 3 weeks of gestation, tetralogy of Fallot at 3-7 weeks, and omphalocele at 6-10 weeks. A single noxa acting at 3 weeks could have caused sequential malformations that initially seem unrelated.

Abnormalities, Multiple↗

A hereditary cancer consultation clinic.

There is a significant hiatus between existing knowledge about hereditary forms of cancer and the application of this information at the bedside. We believe that the HCCC concept will effectively bridge this gap between medical knowledge and its service application. Priority areas for assuring long-range success of this mission will require: a) greater public and physician awareness of the hereditary portion of the total cancer problem; b) generation of cost-benefit information relevant to the surveillance and management of patients at risk for hereditary cancer so that third party carriers might be more responsive to patient needs: c) enhancement of patient/family compliance with surveillance/management protocols leading to early detection of cancer and improved survival; and d) research into biomarkers which demonstrate acceptable sensitivity and specificity for the cancer-prone genotype, one day enabling identification of the deleterious gene(s). Thus, we may achieve the ultimate goal of identifying biochemical agents which will effectively ameliorate the deleterious products of the cancer-prone gene(s), improve clinical outlook, or even prevent cancer expression.

Adult↗

Breast cancer family history as a risk factor for early onset breast cancer.

Since full breast cancer screening is not generally recommended for young women, it is important to identify individuals who are at higher risk for early onset breast cancer. We investigated the relationship between age of onset of breast cancer in 328 probands (consecutively ascertained patients from our oncology clinic) and breast cancer incidence and age of onset in their female relatives. We found that a family history of early onset breast cancer was associated with higher risk of early onset breast cancer. A family history of early onset breast cancer occurred more frequently among young (less than 40) breast cancer probands than among older (greater than or equal to 40) breast cancer probands (p less than 0.001; OR = 23). This relationship was particularly evident when the analysis was restricted to the hereditary breast cancer probands (p less than 0.001; OR = 44). We also observed a positive family history of breast cancer (any age) more frequently in young breast cancer probands than in older breast cancer probands (p less than 0.001; OR = 2.8). These observations have important pragmatic implications for surveillance. We recommend intense surveillance for breast cancer, initiated earlier, for women with close relatives diagnosed with early onset breast cancer.

Adult↗

Myocardial infarction and normal coronary arteriography: a 10 year clinical and risk analysis of 74 patients.

Myocardial infarction with normal coronary arteries was identified in 74 patients with a mean age of 43 years (range 19 to 66). A mean follow-up period of 10.5 years after documented myocardial infarction and 8.6 years after cardiac catheterization was obtained. The survival rate was 85% (n = 63). There were no statistical differences in age or clinical risk factor prevalence between survivors and nonsurvivors. Moderate (55%) to severe (27%) left ventricular impairment was more common in nonsurvivors. Nine of 11 deaths were cardiovascular, 6 were sudden and 8 occurred in patients with moderate to severe global left ventricular impairment. Seventy-six percent of survivors were asymptomatic and 86% were fully active at follow-up. Two survivors and three nonsurvivors experienced a second myocardial infarction. The clinical risk factors of the study group (Group I) were compared by age, sex and year of catheterization with risk factors in two matched groups. Group II consisted of 74 patients with coronary occlusive disease and myocardial infarction and Group III consisted of 148 patients with normal arteriograms. Group I differed from Group II in having fewer clinical risk factors (p = 0.01 to less than 0.0001). Cigarette smoking did not differ significantly between Group I (72%) and Group II (69%) but was less common in Group III (45%) (p less than 0.001). Hormone therapy or the peripartum state was more common in women in Group I (34%) than in women in Group III (14%) (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Salinity affects intracellular calcium in corn root protoplasts.

Previous work with the fluorescent Ca probe chlorotetracycline (CTC) showed that salinity displaces Ca from membranes of root cells. Using a variety of indirect approaches, we studied whether salinity displaces Ca from the cell surface or from internal membranes of corn (Zea mays L. cv Pioneer 3377) root protoplasts. Preloading the cells with supplemental Ca counteracted subsequent NaCl effects on CTC fluorescence. CTC quenching by exogenous EGTA was not competitive with CTC quenching by NaCl. The Ca channel reagent (+)-202-791 had significant interactions with the effect of NaCl on CTC fluorescence. The effect of NaCl on CTC fluorescence was attenuated by pretreatment with Li, but was restored by inositol. Salinity increased Na influx, decreased Ca influx, and increased Ca efflux from the cells. Fluorescence anisotropy indicated that NaCl decreased the fluidity of the external face of the plasmalemma but increased the fluidity of cell membranes in general. Our results suggest that salinity displaces Ca associated with intracellular membranes through activation of the phosphoinositide system and depletion of intracellular Ca pools.

Journal Article↗