Search PubMed⌕ Search

Biomedical subjects

J M Alexander

Publications and source records attributed to J M Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hyperbaric oxygen therapy for nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To evaluate the effectiveness of hyperbaric oxygen therapy in reducing optic nerve damage in acute nonarteritic anterior ischemic optic neuropathy. METHODS: Twenty-two eyes in 20 patients with acute nonarteritic anterior ischemic optic neuropathy were treated with hyperbaric oxygen (100% oxygen, 2.0 absolute atmospheres of pressure) in two 90-minute inhalation sessions per day for ten days. Changes in mean visual acuity and mean sensitivity loss were compared with those of 27 untreated control patients with acute nonarteritic anterior ischemic optic neuropathy, and proportions of patients with a change in acuity or mean sensitivity loss were compared with controls. Similar analysis was performed on subgroups based on time delay from symptom onset to therapy. RESULTS: Mean values for visual acuity were increased at final examination in both groups; although the increase was greater in controls, the difference was not statistically significant. Mean visual field sensitivity loss was minimally increased; although the increase was smaller in controls, the difference between groups was not significant. There was no significant difference between groups in proportions of patients with change in acuity score or mean sensitivity loss. Stratification by time delay to therapy did not suggest that treatment within nine days produced better visual results than that for either controls or those treated later. CONCLUSIONS: Hyperbaric oxygen therapy using 100% oxygen and 2.0 absolute atmospheres of pressure did not produce a significant improvement in visual acuity or visual field for patients with acute nonarteritic anterior ischemic optic neuropathy.

Acute Disease↗
PubMed1996

Clinical course of premature rupture of the membranes.

Premature rupture of the membranes (PROM), defined as rupture of the membranes before the onset of labor, is a common obstetric event occurring in 10% of pregnancies. Most of the time this occurs at or beyond 37 weeks' gestation with only 10% of PROM occurring at less than 37 weeks' gestation. The natural course of PROM is labor, and at term this is associated with a low rate of complications for the mother and the fetus. At less than 37 weeks' gestation PROM places the mother and the fetus at increased risk of short-term and long-term morbidity and mortality. Several factors related to preterm premature rupture of the membranes (PROM) add risk to the pregnancy and include premature delivery, infection in the mother and the fetus, effects of prolonged oligohydramnios on fetal development, abruptio placenta, prolapsed cord, and fetal malposition. Since the 1970s expectant management has been the standard treatment for PROM; however, in the majority of patients, this strategy results in the delivery of a preterm infant. In addition, controversy exists over the gestational age at which expectant management should be abandoned and active interventions to effect delivery pursued. This article discusses the natural history of PROM, the outcome of expectant management in PROM, and maternal and fetal outcomes in these patients. The emphasis of this discussion is on the preterm fetus.

Female↗
PubMed1996

Gonadotropin-releasing hormone messenger RNA expression in gonadotroph tumors and normal human pituitary.

Gonadotroph tumors predominantly secrete FSH or free gonadotropin hormone subunits and rarely LH. In contrast to normal gonadotrophs, a subset of tumors synthesize FSH beta-subunit (SU) in excess of alpha-SU, and the cause of gonadotropin hormone-SU biosynthetic defects in these tumors is unknown. Gonadotropin-releasing hormone (GnRH) is known to modify gonadotropin hormone-SU biosynthesis and secretion and may be an important determinant of gonadotroph tumor hormone regulation. Data in experimental animals have demonstrated that endogenous expression of GnRH may occur in the pituitary. We therefore determined whether 1) the GnRH gene is expressed in gonadotroph tumors and normal pituitaries using reverse transcriptase (RT)-PCR; 2) the GnRH receptor gene is co-expressed in gonadotroph tumors; 3) an alternative upstream transcriptional start site on the GnRH gene is utilized; and 4) media from primary cultures of gonadotroph tumors have detectable GnRH immunoreactivity by RIA. GnRH messenger RNA (mRNA) was detected in 10/10 gonadotroph tumors, eight of which expressed GnRH-Receptor mRNA. Both mRNAs were detected in all normal pituitaries studied (n = 6). Six of 10 gonadotroph tumors and 3/6 normal pituitaries had GnRH transcripts derived from the upstream transcriptional start site (5'GnRH). GnRH immunoreactivity was detected in overnight media from 3/3 primary gonadotroph tumor cultures (range: 1.89-5.86pg/mL; limit of detection (LD) = < 1.58pg/mL) but was not detectable in control media. This is the first study to demonstrate endogenous GnRH gene expression in human pituitary adenomas and normal human pituitary tissue. The presence of both GnRH and GnRH-Rc suggest that GnRH may be a paracrine/autocrine regulator of cell function in the pituitary and may affect gonadotroph tumor hormone phenotype.

Adenoma↗
PubMed1996

Tumor-specific expression and alternate splicing of messenger ribonucleic acid encoding activin/transforming growth factor-beta receptors in human pituitary adenomas.

Activin, a member of the transforming growth factor-beta (TGF beta) cytokine family, acts as a pituitary cell mitogen via a novel family of receptor-linked serine/threonine (Ser/Thr) kinases. Pituitary tumors synthesize activin subunits, and the autocrine action of these growth factors may modulate tumor proliferation. We, therefore, investigated the expression of activin/TGF beta type I receptor messenger ribonucleic acids (mRNAs), designated ALK1 through ALK5 (ALK = activin receptor-like kinase), and type II receptor mRNAs using RT-PCR in 34 human pituitary adenomas of all phenotypes and normal pituitary tissue. ALK2 and ALK5, specific mediators of activin and TGF beta signals, respectively, were found to be expressed only in tumor and not in normal pituitary cells, and ALK2 expression was found only in tumors of a mammosomatotroph cell lineage. ALK1, ALK3, and ALK4 mRNAs were found in both normal and neoplastic pituitary cells. The alternatively spliced cytoplasmic domain of ALK4 consists of 11 kinase subdomains, that are critical for modulating receptor function and intracellular signaling. Truncated forms of the ALK4 cytoplasmic domain lacking these subdomains may attenuate activin signal transduction and affect both tumor phenotype and proliferation via the formation of inactive type I/type II complexes. Three truncated ALK4 receptor mRNAs generated by alternate splicing of the cytoplasmic Ser/Thr kinase domain were found to be tumor specific. One of these truncated receptor mRNAs, ALK4-5, is a novel splice variant that has not been previously described. Expression of the ActRII and T beta RII type II receptor mRNAs, which specifically bind activin and TGF beta, respectively, was highly prevalent among all tumor subtypes and normal pituitary tissue. However, ActRIIB, an activin-specific type II receptor that displays a 3- to 4-fold higher affinity for ligand than ActRII, was expressed in 94% of tumors, but was not prevalent in normal tissue. These data are the first to demonstrate tumor-specific expression of Ser/Thr kinase receptors mRNAs and their splice variants in human pituitary adenomas.

Activin Receptors↗
PubMed1995

Use of reduced-calorie/reduced-fat foods by young adults: influence of gender and restraint.

Reduced-calorie/reduced-fat (RC/RF) foods are widespread in the food supply, but there are few published data on who is using them and why. A total of 226 college men (n = 76) and women (n = 150) participated in a survey investigating the influence of gender and dietary restraint on eating habits, dieting and the use of 11 categories of RC/RF foods. Men did not differ from women in their overall use of RC/RF foods, although specific foods were consumed by a greater percentage of women. Restrained eating was strongly related to use of all the foods (p < or = 0.001). Women and those higher in restraint used the foods primarily for weight-control purposes, whereas men and those lower in restraint tended to use the foods for both weight control and other reasons. Women and those high in restraint were also more likely to have changed their eating habits to achieve weight loss and maintenance goals and to achieve a healthier lifestyle. In contrast, a greater percentage of men and those low in restraint wanted to achieve weight gain. These data suggest that RC/RF foods were popular among respondents in the study, but that the reasons for their use by restrained and unrestrained eaters might reflect gender differences in body weight and health concerns.

Adult↗
PubMed1995

Multifetal reduction of high-order multiple pregnancy: comparison of obstetrical outcome with nonreduced twin gestations.

OBJECTIVE: To compare the obstetric outcomes of twin pregnancies obtained as a result of multifetal pregnancy reduction to those in which pregnancy reduction had not been used. DESIGN: Retrospective analysis. SETTING: University-based tertiary care infertility clinic. PATIENTS: Seventy-four twin pregnancies continuing beyond 10 weeks. Of these, 32 gestations had undergone reduction to twins at 10 weeks. MAIN OUTCOME MEASURES: Gestational age at delivery, birth weights, pregnancy complications. RESULTS: All pregnancies advanced beyond 20 weeks gestation. The mean gestational age at delivery of the reduction group was 33.8 versus 35.7 weeks in the nonreduced group; only 25% of reduced pregnancies reached 37 weeks compared with 57.9% of nonreduced twins. The mean fetal birth weights of the two groups differed significantly (reduced: 2,038 g, nonreduced: 2512 g). The gestational age at delivery in patients reduced from triplets was significantly greater than in pregnancies reduced from quadruplets or higher. Multiple regression analysis revealed that for a given gestational age at delivery, a history of pregnancy reduction was associated with decreased birth weight. CONCLUSION: These data suggest that multifetal pregnancy reduction does not reverse completely the decreased gestational age and impaired fetal growth associated with high-order multiple pregnancy. Furthermore, fetal growth of reduced pregnancies seems to be impaired independent of the gestational age at which delivery occurs.

Adult↗
PubMed1995

Human pituitary adenomas express endogenous inhibin subunit and follistatin messenger ribonucleic acids.

Specific factors involved in the pathogenesis of tumors that stimulate clonal human pituitary adenoma cell proliferation remain unknown. An important question regarding the pathogenesis of human pituitary tumors is whether they synthesize autocrine regulatory factors that regulate both hormone biosynthesis and neoplastic growth. Activin and inhibin are both comprised of inhibin subunits and have diverse regulatory roles as growth and differentiation factors in normal and neoplastic tissue. Activin stimulates FSH beta messenger ribonucleic acid (mRNA) biosynthesis and FSH secretion, and these effects are down-regulated in normal gonadotrophs by the endogenous glycoprotein follistatin. In addition to its effects on gonadotrophs, activin modulates hormone secretion by somatotroph and corticotroph cell lines. It is not known whether human neoplastic pituitary tissue synthesizes inhibin subunits or follistatin or whether their expression is cell type specific. We investigated whether alpha-, beta A-, and beta B-inhibin subunit and follistatin mRNAs could be detected in 27 human pituitary adenomas [clinically nonfunctioning (n = 11), somatotroph (n = 5), corticotroph (n = 5), and lactotroph (n = 6)] using reverse transcriptase-polymerase chain reaction techniques. Twenty-six of the tumors contained mRNAs encoding one or more inhibin subunits. beta B-Inhibin mRNA was the most prevalent (81% of tumors), followed by beta A-inhibin (59% of tumors) and alpha-inhibin (52% of tumors). Endogenous alpha-, beta A-, and beta B-inhibin subunit mRNA synthesis was also examined in normal human pituitary and testicular complementary DNA libraries, and all subunit mRNAs were detected. In contrast to the widespread expression of inhibin subunits in pituitary tumors, follistatin mRNA was detected in a subset of nonfunctioning tumors (54%) as well as in control normal human pituitary and testicular complementary DNA libraries. Tumor-specific follistatin biosynthesis was not observed in other pituitary tumor subtypes. These data are the first to demonstrate that 1) endogenous inhibin subunits are synthesized in human pituitary adenomas of all known secretory phenotypes as well as normal pituitary tissue; and 2) follistatin gene expression in pituitary adenomas is specific to clinically nonfunctioning or gonadotropin subunit-producing tumors. The characterization of inhibin subunit and follistatin biosynthesis by human pituitary tumors will be important in investigating their potential roles in regulating both tumor phenotype and cell proliferation.

Adenoma↗
PubMed1995

Somatostatin receptor subtype gene expression in pituitary adenomas.

Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA, which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5 mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application.

Adenoma↗
PubMed1994

Gonadotropin-releasing hormone receptor mRNA expression by human pituitary tumors in vitro.

An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin-releasing hormone (GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10(-8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude (a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors.

Aged↗
PubMed1994

ras mutations in human prolactinomas and pituitary carcinomas.

Pituitary adenomas have been shown to be clonal in origin, indicating that one or more somatic mutations underlie tumor pathogenesis. Mutated oncogenic forms of ras protein have been identified in a number of human neoplasms, including thyroid adenomas and carcinomas. However, the potential role of activated ras in the development of specific human pituitary tumor phenotypes has not been determined. Although ras mutations were not found in glycoprotein hormone-secreting or somatotroph adenomas, we recently identified a mutation in the H-ras gene (Gly-Val) at codon 12 in a highly invasive prolactinoma. These data raise the possibility that ras mutations might play a role in the pathogenesis of PRL-secreting pituitary tumors and/or may be a marker for tumor invasiveness and malignant transformation. Therefore, we investigated 78 pituitary tumors (59 prolactinomas, 13 invasive prolactinomas, and 6 pituitary carcinomas) for activating point mutation in the three ras genes using oligonucleotide-specific hybridization. In contrast to the relatively high frequency of ras mutations in many different tumor types, no ras mutations were identified in either prolactinomas or pituitary carcinomas. Our data indicate that ras mutations are rare in prolactinomas and pituitary carcinomas.

Adolescent↗
PubMed1993

The retinoblastoma gene in human pituitary tumors.

Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, we studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotroph adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors.

Adenoma↗
PubMed1992

Randomised controlled trial of breast shells and Hoffman's exercises for inverted and non-protractile nipples.

OBJECTIVE: To determine the value of recommending breast shells or Hoffman's exercises, or both, to pregnant women with inverted or non-protractile nipples who intend to breast feed. DESIGN: Randomised controlled trial with a two treatment by two level factorial design. SETTING: Antenatal clinics in a district general hospital and the community. SUBJECTS: 96 nulliparous women recruited between 25 and 35 completed weeks in a singleton pregnancy with at least one inverted or non-protractile nipple. MAIN OUTCOME MEASURES: Anatomical change of nipples, judged blindly before first breast feeding, and success of breast feeding reported by postal questionnaire six weeks postnatally. RESULTS: Sustained improvement in nipple anatomy was more common in the untreated groups but the differences were not significant (52% (25/48) shells v 60% (29/48) no shells; difference -8% (95% confidence interval -28% to 11%) and 54% (26/48) exercises v 58% (28/48) no exercises; -4% (-24% to 16%)). 24 (50%) women not recommended shells and 14 (29%) recommended shells (21%; 40% to 2%) were breast feeding six weeks after delivery (p = 0.05), reflecting more women recommended shells both deciding to bottle feed before delivery and discontinuing breast feeding. The same number of women in exercise and no exercise groups were successfully breast feeding (0%; -20% to 20%). 13% of women approached about the trial (and planning to breast feed) did not attempt breast feeding. CONCLUSIONS: Recommending nipple preparation with breast shells may reduce the chances of successful breast feeding. While there is no clear evidence that the treatments offered are effective antenatal nipple examination should be abandoned.

Adolescent↗
PubMed1992

Legal reality for physicians.

The practice of medicine as we have known it is rapidly becoming a "dinosaur" giving way to more complex business and legal relationships among physicians. Quality medical care, however, does not have to become obsolete. As physicians begin to collaborate with each other to survive and thrive in an increasingly competitive environment, their collective influence over payors and other guardians of the cost of health care should focus on ensuring the preservation of quality medical care. By minimizing the adverse consequences of administrative burdens on individual practices, physicians should be able to maximize their practice efficiency and earning potential while preserving their goal of providing quality medical care.

Antitrust Laws↗
PubMed1992

Ras mutations in human pituitary tumors.

The cellular basis for pituitary neoplasia is poorly understood. Mutations that activate the ras protooncogenes have been identified in a number of different types of human cancers and potentially represent one of the genetic alterations that occur in pituitary tumors. In this study we examined 19 pituitary tumors for the occurrence of ras mutations. The tumor types included 11 nonfunctioning adenomas, 6 somatotroph adenomas, and 2 prolactinomas. Each of the three ras genes (K-ras, N-ras, and H-ras) was amplified from pituitary tumor DNA using the polymerase chain reaction. Oligonucleotide-specific hybridization was used to screen for mutations that inhibit GTPase activity and cause activation of the ras oncogene. No ras mutations were observed in 18 of the pituitary adenomas. However, a mutation was identified in codon 12 of the H-ras gene (Gly to Val) in a recurrent prolactinoma that was highly invasive and ultimately proved to be fatal. We conclude that ras mutations are uncommon in pituitary adenomas, but may provide a marker for highly invasive tumors.

Adenoma↗
PubMed1992

Imbalanced follicle-stimulating hormone beta-subunit hormone biosynthesis in human pituitary adenomas.

Clinically nonfunctioning pituitary adenomas represent approximately 25% of all pituitary tumors. Recent studies using a number of in vitro techniques show that the majority of such tumors produce gonadotropins. Hypersecretion of uncombined gonadotropin subunits by these tumors has also been identified raising the possibility that gonadotropin biosynthetic alterations may occur in neoplastic pituitary tissue. To determine whether underlying intracellular biosynthetic alterations lead to imbalanced secretion of the gonadotropin subunits by such tumors, we investigated 1) steady state gonadotropin-subunit messenger ribonucleic acid (mRNA) levels in tumor tissue from 49 patients with clinically nonfunctioning adenomas, 2) secretion of gonadotropins in dispersed pituitary tumor cultures, and 3) serum concentrations of gonadotropins and free subunits. Northern blots of RNA extracted from surgically obtained pituitary tumor tissue were hybridized with complementary DNA probes for FSH beta, LH beta, and alpha-subunit, and quantitative analysis was done to compare alpha- and beta-subunit biosynthesis in individual tumors. Of these tumors, 47 contained sufficient RNA for Northern analysis and 77% of these tumors contained one or more of the gonadotropin-subunit mRNAs. Steady state alpha-subunit mRNA was detected in 57% of tumors, FSH beta mRNA in 49%, and LH beta in 1 (2%). We found FSH beta mRNA in excess of alpha-subunit mRNA in one-third of tumors, including 9 tumors where alpha-subunit mRNA was undetectable. In cultured cells, FSH beta was secreted in excess of alpha-subunit in 41% of tumors. For those tumors in which both mRNA and culture data were available, FSH beta mRNA and secreted subunit levels were in excess of alpha-subunit in 64% of tumors. We conclude that clinically nonfunctioning pituitary adenomas frequently synthesize excess FSH beta subunit relative to alpha-subunit. This finding is in contrast to previous data in normal pituitary or placental tissue where alpha-subunit is present in excess of beta-subunits at both the mRNA and protein levels. The free-beta-subunit hypersecretion identified in pituitary adenomas may be due to biosynthetic abnormalities intrinsic to neoplastic gonadotrophs.

Adenoma↗