Muscle spindle signals combine with the sense of effort to indicate limb position.

Experiments were carried out to test the hypothesis that, in the absence of vision, position sense at the human forearm is generated by the combined input from muscle spindles in elbow flexor muscles and signals of central origin giving rise to a sense of effort. In a forearm position-matching task, to remove a possible contribution from the sense of effort, the reference arm was held supported at the test angle. Subjects were less accurate in matching elbow position of the supported forearm than when it was unsupported. Adding a 2 kg weight to the unsupported reference arm led subjects to make matching errors consistent with an increase in the effort signal. Evidence of a contribution from muscle spindles was provided by showing that the direction of position matching errors could be systematically altered by flexion or extension conditioning of the reference arm before its placement at the test angle. Such changes in errors with conditioning could be shown to be present when the reference arm was supported, unsupported, or unsupported and weighted. It is concluded that both peripheral signals from muscle spindles and signals of central origin, associated with the motor command required to maintain arm position against the force of gravity, can provide information about forearm position.

The assessment of hookworm calreticulin as a potential vaccine for necatoriasis.

A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm-induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43-49% fewer worms in their lungs, compared to non-vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 microg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti-calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin-loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.

[Renal insufficiency due to light chain multiple myeloma]. / Nierinsufficiëntie door neerslag van lichte ketens bij multipel myeloom.

In 3 female patients, aged 65, 83 and 76 years, with severe renal failure, light chain multiple myeloma was diagnosed, following a substantial delay on the part of the doctors concerned. Either the diagnosis had not suspected or the serum proteins had been misinterpreted. After a while, the first two patients declined further treatment with chemotherapy and haemodialysis, and subsequently died. The third patient attained a creatinine clearance of 20 ml/min and was subsequently treated for the multiple myeloma in the outpatients department. The absence of a paraprotein peak in the serum does not exclude the possibility of a multiple myeloma. In the case of light chain disease, the gammaglobulin region is, in fact, often empty. Treatment of multiple myeloma consists of a rapid rehydration and forced diuresis; the usefulness of plasmapheresis has not been demonstrated.

Androstenedione treatment of pregnant baboons at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal maternal plasma estradiol surge relative to progesterone and increases myometrial contraction activity.

Androstenedione treatment of pregnant monkeys at 0.8 of gestation reproduces endocrine, biophysical, and biochemical changes similar to those measured during spontaneous, term labor in the pregnant monkey. In the pregnant baboon, the spontaneous onset of labor at term has been attributed to a forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma. This study investigated whether androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal surge of maternal plasma estradiol relative to progesterone and whether this shift is associated with premature increases in nocturnal myometrial activity. Eight pregnant baboons were prepared surgically under general anesthesia with vascular catheters and myometrial electromyogram electrodes between 121 and 139 days of gestation (term is ca. 185 days). Catheters were maintained patent by continuous infusion of heparinized saline from the time of surgery until one of two treatments began following at least 9 days of postoperative recovery. In four baboons (Group I), the saline administration was replaced by a continuous infusion of 10% intralipid vehicle during Day 1 of the experimental protocol. During Day 2 and Day 3, the intralipid infusion was switched for a continuous infusion of androstenedione dissolved in intralipid set at a low (0.8 mg x kg(-1) x h(-1)) and at a high (1.6 mg x kg(-1) x h(-1)) dose, each delivered for 24 h. The other four pregnant baboons (Group II) received 10% intralipid vehicle for Days 1, 2, and 3 of the experimental protocol. One baboon from Group I received an additional dose of 0.4 mg x kg(-1) x h(-1) for 24 h before the low and the high dose of androstenedione. In each baboon, during each experimental day, maternal arterial blood samples (1 ml) were taken at 1 h intervals for 12 h, starting 3 h before the onset of darkness in the animal's environment, for measurement of maternal plasma estradiol and progesterone concentrations via RIA. Myometrial contractions were counted during each night-time period of the experimental protocol. All pregnant baboons demonstrated increases in maternal plasma estradiol and progesterone concentrations at night-time. Androstenedione had a dose-dependent effect in elevating day-time maternal plasma estradiol concentrations and in promoting a forward shift in the nocturnal surge of maternal plasma estradiol without affecting the nocturnal progesterone profile in maternal plasma. Maternal treatment with androstenedione also led to an increase in nocturnal myometrial contraction activity. We conclude that androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma and that this shift is associated with an increase in nocturnal myometrial contraction activity, in a similar way to that measured during spontaneous onset of labor at term in this species.

Doctor, can we talk? Physician-patient communication issues that could jeopardize patient trust in the physician.

The essences of the prostate cancer experience were explored through interviews with ten early-stage prostate cancer patients who were approximately one year post surgical treatment. One theme that emerged from this modified phenomenological study dealt with the relationships patients had with their physicians. One of the major concerns expressed by the study participants was a lack of communication with their physicians. The study provides evidence that physicians and other healthcare providers should work more diligently with patient communication in order to provide patients with a full understanding of their disease, treatment options, and potential adverse outcomes from treatment.

Opposing effects of androgen and estrogen on pituitary-adrenal function in nonpregnant primates.

Maternal administration of androstenedione produces a sustained fall in maternal plasma adrenocorticotropic hormone (ACTH) concentrations in the pregnant nonhuman primate. We hypothesize a negative feedback influence on the maternal hypothalamo-pituitary-adrenal (HPA) axis by androgens in primates. This may reflect an important maternal adaptation during pregnancy in primates preventing premature induction of labor by maternal stress. However, androstenedione is precursor for placental estradiol-17beta synthesis, and infusion of androstenedione into pregnant primates elevates maternal plasma estradiol-17beta to term concentrations. Thus, it could be argued that 1) the effects attributed to androstenedione on the maternal HPA axis are mediated by estrogen rather than by androgen and 2) the negative influence of androgens may be on placental ACTH rather than, or in addition to, pituitary ACTH. To discriminate between androgenic and estrogenic effects of androstenedione on pituitary and/or placental ACTH function in primates we measured plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations in nonpregnant baboons after treatment with either androstenedione or estradiol-17beta. Nine female baboons were studied between 14 and 22 days postpartum prior to estrous cycling. After 2 days of baseline, a continuous i.v. infusion of androstenedione (1.5 mg/kg per h in 10% intralipid, IL) was started at 0900 h and maintained for 9 days in 3 baboons. A similar protocol was carried out in another 3 baboons that received a continuous i.v. infusion of estradiol-17beta (10 microg/kg per h in 10% IL) instead of androstenedione. Three additional baboons received continuous i.v. IL vehicle alone and served as controls. Arterial blood samples (0.5 ml) for measurement of plasma hormones were taken during baseline and after 1, 3, 5, 7, and 9 days of infusion. Baseline plasma ACTH, DHEAS, and cortisol concentrations were similar among all groups. Plasma ACTH did not change during IL, increased following estradiol-17beta, and fell during androstenedione treatment. Accordingly, plasma cortisol and DHEAS concentrations were also unaltered by IL, and both steroids increased during estradiol-17beta treatment. In contrast, plasma cortisol and DHEAS remained unaltered from baseline during androstenedione treatment, despite the fall in plasma ACTH measured at this time. These data in the nonpregnant baboon 1) are consistent with negative feedback on pituitary ACTH by androgens and 2) demonstrate a positive influence on pituitary-adrenal function by estrogen in primates.

Semirational design of a potent, artificial agonist of fibroblast growth factor receptors.

Fibroblast growth factors (FGFs) are being investigated in human clinical trials as treatments for angina, claudication, and stroke. We designed a molecule structurally unrelated to all FGFs, which potently mimicked basic FGF activity, by combining domains that (1) bind FGF receptors (2) bind heparin, and (3) mediate dimerization. A 26-residue peptide identified by phage display specifically bound FGF receptor (FGFR) 1c extracellular domain but had no homology with FGFs. When fused with the c-jun leucine zipper domain, which binds heparin and forms homodimers, the polypeptide specifically reproduced the mitogenic and morphogenic activities of basic FGF with similar potency (EC50 = 240 pM). The polypeptide required interaction with heparin for activity, demonstrating the importance of heparin for FGFR activation even with designed ligands structurally unrelated to FGF. Our results demonstrate the feasibility of engineering potent artificial agonists for the receptor tyrosine kinases, and have important implications for the design of nonpeptidic ligands for FGF receptors. Furthermore, artificial FGFR agonists may be useful alternatives to FGF in the treatment of ischemic vascular disease.

Secondary lymphoid-tissue chemokine (SLC) is chemotactic for mature dendritic cells.

Dendritic cells (DC) take up antigen from the periphery and migrate to the lymphoid organs where they present the processed antigens to T cells. The propensity of DC to migrate changes during DC maturation and is probably dependent on alterations in the expression of chemokine receptors on the surface of DC. Secondary lymphoid tissue chemokine (SLC), a recently discovered chemokine for naïve T cells, is primarily expressed in secondary lymphoid organs and may be important for colocalizing T cells with other cell types important for T-cell activation. We show here that SLC is a potent chemokine for mature DC but does not act on immature DC. SLC also induced calcium mobilization specifically in mature DC. SLC and Epstein-Barr virus-induced molecule 1 ligand chemokine completely cross-desensitized the calcium response of each other, indicating that they share similar signaling pathways in DC. The finding that SLC is a potent chemokine for DC as well as naïve T cells suggests that it plays a role in colocalizing these two cell types leading to cognate T-cell activation.

Changes in fetal plasma corticotropin-releasing hormone during androstenedione-induced labor in the rhesus monkey: lack of an effect on the fetal hypothalamo-pituitary-adrenal axis.

Androstenedione infusion to pregnant monkeys leads to premature labor and live delivery. Androstenedione-induced labor also increased placental CRH messenger RNA and peptide to concentrations observed at term in pregnant monkeys. Placental CRH may modulate fetal pituitary-adrenal function during pregnancy in primates. This study tested the hypothesis that androstenedione-induced premature delivery in pregnant monkeys results from androstenedione-induced increases in placental CRH, which stimulate premature activation of the fetal pituitary-adrenal axis. The hypothesis was tested by comparing fetal umbilical vein (FUV) plasma CRH, ACTH, dehydroepiandrosterone sulfate, and cortisol concentrations at cesarean section in fetuses from mothers undergoing spontaneous, term labor (group I), with those in fetuses from mothers undergoing androstenedione-induced, premature labor (group II) and with those from mothers not in labor (group III). In addition, gestation-related changes in maternal plasma CRH concentrations were investigated, and CRH immunoactivity was characterized by Sephadex G50 chromatography in pooled maternal plasma extracts. FUV CRH concentrations were similarly elevated in group I and group II fetuses, compared with group III fetuses. Despite similar FUV blood gases in all fetuses, FUV ACTH and dehydroepiandrosterone sulfate concentrations were higher in group I fetuses than in group II or group III fetuses. The majority of CRH immunoactivity coeluted with synthetic human CRH. Maternal plasma CRH concentrations showed a modest increase with gestation in the rhesus monkey. These data: 1) demonstrate that androstenedione treatment of pregnant monkeys at 0.8 of gestation elevates fetal plasma CRH to similar concentrations measured at term; 2) do not support the hypothesis that androstenedione-induced delivery in the monkey results from premature activation of the fetal pituitary-adrenal axis by placental CRH; but 3) do support a role for activation of the fetal hypothalamo-pituitary-adrenal axis in association with spontaneous term labor in the monkey; and 4) demonstrate important interprimate species differences in maternal CRH physiology.

Local paracrine effects of estradiol are central to parturition in the rhesus monkey.

The central biochemical mechanisms involved in primate parturition are still unclear. Studies in both humans and nonhuman primates such as the baboon and rhesus monkey indicate that many factors play a part in the cascade of interactive positive feedforward loops that progressively promote parturition: changes in maternal endocrinology, a nocturnal switch in myometrial activity from low amplitude, infrequent contractures to high amplitude, high frequency contractions (see Fig. 1), dilation of the cervix and biochemical changes in the fetal membranes that lead to rupture. Here we demonstrate that infusion of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA) inhibits conversion of androgen to estrogen and prevents premature delivery caused by administration of androgen to pregnant rhesus monkeys at 0.8 of pregnancy term. 4OHA also inhibited the androstenedione induced maternal endocrine and fetal membrane biochemical changes, and alteration of myometrial activity patterns. Secondly, peripheral estrogen infusions increased myometrial activity but did not produce preterm delivery or fetal membrane changes. We conclude that paracrine functions of estrogen at its site of production play critical and central roles in delivery in the non-human primate.

Fetal growth in the baboon during the second half of pregnancy.

The normal growth profile of critical fetal organs through the last third of gestation has not been documented in detail in human fetuses or the fetus of any nonhuman primate species. Recent epidemiological studies in human pregnancy suggest that fetal growth plays a major role in the programming of life-long health by modifying cardiovascular, pancreatic, brain, and liver growth. The present study aimed to produce a detailed database of individual organ growth in the fetal baboon in late gestation. Fetal organ weights were obtained from 43 baboon fetuses between 121 and 177 days of gestation. Various organs (brain, heart, kidney, femur, intestines, and spinal cord) showed no sign of slowed growth in late gestation while growth of others (lung, liver, stomach, and bladder) accelerated in late gestation. The fetal adrenal and thymus showed a decrease in growth rate over the final 20 and 10 days of gestation respectively. These observations provide a database that will permit analysis of factors responsible for regulation of normal and altered fetal organ development in this important experimental species.

Proteinuric hypertension in a pregnant baboon: was this pre-eclampsia?

We report the results of investigating a pregnant baboon that developed hypertension, proteinuria, and oedema in late gestation. Although the clinical presentation suggested a diagnosis of pre-eclampsia, the evolution of her clinical signs and results of a renal biopsy performed 3 weeks after delivery suggested that glomerulonephritis was the underlying disease.

Timing of the switch from myometrial contractures to contractions in late-gestation pregnant rhesus monkeys as recorded by myometrial electromyogram during spontaneous term and androstenedione-induced labor.

Pregnant rhesus monkeys were studied to determine the precise time in relation to photoperiod of the onset, and the nature, of the switch in myometrial activity patterns from contractures to contractions. We investigated both spontaneous term labor and androstenedione-induced preterm labor. Under general anesthesia at 127 +/- 2 days gestation (dGA) (mean +/- SEM), 16 pregnant rhesus monkeys were instrumented with maternal femoral arterial and venous catheters and myometrial electromyogram electrodes. Eight animals (group I) received continuous i.v. infusion of intralipid (n = 7) or saline (n = 1) that was started at 143.3 +/- 2 dGA and maintained until the spontaneous onset of term labor. Nine animals (group II) received continuous i.v. infusion of androstenedione that was started at 139 +/- 0.4 dGA and maintained until the onset of prematurely induced labor. Myometrial activity was recorded continuously. All monkeys in both groups demonstrated nocturnal switches in myometrial activity from contractures to contractions. The mean time of onset of the switch in group I and group II monkeys was similar, occurring at 0.7 +/- 0.4 h or 0.8 +/- 0.5 h, respectively, after the onset of darkness. Group II monkeys demonstrated greater regularity in both the time of onset and the repetitive occurrence each night once the switch occurred, as well as greater consistency in duration in their switch patterns, than did group I monkeys.

Relationship between androstenedione-induced myometrial contractions and platelet-activating factor acetylhydrolase in late gestation in pregnant rhesus monkeys.

An association between platelet-activating factor (PAF) and myometrial contractions has been established. Estrogens regulate PAF activity via reduction in the activity of plasma PAF acetylhydrolase (PAF-AH), the enzyme that catalyzes PAF inactivation. Administration of androstenedione to pregnant monkeys leads to sustained increases in maternal plasma estradiol (E2), with persistent nocturnal myometrial contractions. The present study tested the hypothesis that androstenedione-induced contractions are associated with a fall in maternal plasma PAF-AH activity in monkeys. Eight monkeys (132-136 days gestation, dGA) were instrumented under halothane anesthesia with maternal vascular catheters and uterine electromyogram electrodes. At 138-142 dGA, two baseline maternal arterial samples were taken for E2 and PAF-AH measurements. The following day a continuous i.v. androstenedione infusion was started in 4 monkeys while 4 control monkeys received i.v. infusions of vehicle alone. Arterial blood sampling was repeated 1 and 3 days after the start of either infusion. Despite an increase in maternal E2 to term levels and established myometrial contractions, no change in maternal plasma PAF-AH activity occurred after androstenedione treatment. Maternal plasma E2, PAF-AH activity, and contractions remained unchanged from baseline in control monkeys. In conclusion, androstenedione-induced increases in maternal plasma E2 and myometrial contractions are not associated with a fall in maternal plasma PAF-AH specific activity.

Differential effects of betamethasone and dexamethasone fetal administration of parturition in sheep.

OBJECTIVE: We tested the hypothesis that betamethasone is more potent than dexamethasone in inducing the essential mechanisms of parturition in sheep. METHODS: Twenty-one sheep were instrumented under general anesthesia with maternal and fetal arterial and venous catheters and myometrial electromyogram electrodes at 117 days' gestation (dGA). At 125 dGA at 12:00 PM, after 2 days of baseline recording, either saline (n = 7, control group), betamethasone (n = 7), or dexamethasone (n = 7) was administered into the fetal jugular vein at a rate of 10 micrograms/hour. A total dose of 0.48 mg was given over the next 48 hours. The animals underwent autopsy 3 days after the end of the infusion period (130 dGA), or earlier if labor resulted from the glucocorticoid administration. Daily maternal and fetal arterial blood samples (4 mL) for hormone measurement were taken at 10:00 AM throughout the study period. Additional arterial blood samples were taken if the animal developed labor. Maternal plasma progesterone and fetal ACTH and cortisol concentrations were measured by radioimmunoassay, and corticosteroid-binding globulin (CBG) binding capacity was determined by saturation analysis. Myometrial activity was monitored continuously throughout the experimental protocol. RESULTS: All seven betamethasone-treated animals developed labor after the glucocorticoid infusion regimen. In contrast, only two of seven dexamethasone-treated animals developed labor. Fetal treatment with betamethasone produced a greater and earlier fall in maternal plasma progesterone than fetal treatment with dexamethasone. Both betamethasone and dexamethasone treatments elevated fetal plasma CBG to similar binding capacities. Elevated fetal plasma ACTH and cortisol concentrations at the end of the infusion period in both betamethasone-and dexamethasone-treated animals were not related to the development of labor-type contractions. CONCLUSION: These data support the hypothesis that betamethasone is more potent than dexamethasone in inducing the essential mechanisms of parturition in sheep.

The oxytocin antagonist atosiban prevents androstenedione-induced myometrial contractions in the chronically instrumented, pregnant rhesus monkey.

We tested the hypothesis that increased oxytocin is a necessary mechanism for the mediation of androstenedione (delta 4A)-induced myometrial contractions by investigating the effects of maternal treatment with the oxytocin antagonist atosiban on in vivo delta 4A-induced contractions. In four monkeys (group I), maternal estradiol, oxytocin, and myometrial contractions were assessed at baseline and after continuous iv delta 4A administration. Similar measurements were made in three monkeys (group II) that received the same delta 4A infusion regimen, but in addition were treated daily with atosiban. Maternal estradiol and oxytocin levels and contractions were also assessed in four additional monkeys (controls; group III), in which the delta 4A vehicle, intralipid, was infused iv continuously. In group I, delta 4A induced myometrial contractions and increased maternal estradiol and oxytocin to term concentrations. No myometrial contractions occurred in group II monkeys after combined delta 4A and atosiban treatment despite estradiol being elevated to concentrations similar to those measured in group I monkeys. Atosiban had no effect on maternal heart rate or blood pressure. Maternal estradiol, oxytocin, and number of myometrial contractions remained unchanged from baseline values in control monkeys. In conclusion, oxytocin is a necessary part of the mechanisms mediating delta 4A-induced myometrial contractions. delta 4A promotes myometrial contractions via similar mechanisms that mediate spontaneous term contractions in pregnant monkeys.

Daily and hourly temporal association between delta4-androstenedione-induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey.

OBJECTIVE: Our purpose was to investigate the temporal relationship between delta4-androstenedione-induced preterm switching of myometrial activity patterns from contractures to contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey. STUDY DESIGN: Eight rhesus monkeys (132 to 136 days' gestation) were instrumented under halothane with femoral artery and vein catheters and uterine electromyogram electrodes. At 138 to 142 days' gestation baseline maternal femoral artery blood samples for estradiol and oxytocin measurement were taken at 30-minute intervals for 7 hours, starting 2 hours before the onset of darkness. The day after baseline sampling a continuous intravenous delta4-androstenedione infusion (0.3 mg . kg-1 .hr-1 in 10% intralipid at 0.25 ml . hr-1) was started in four monkeys, while four monkeys were infused intravenously with intralipid alone. The sampling regimen was then repeated at 1 and 3 days after the start of the delta4-androstenedione or intralipid infusion. Contractions were counted and estradiol and oxytocin were measured by radioimmunoassay. RESULTS: Androstenedione promoted a premature nocturnal increase in myometrial contractions in conjunction with an increase in maternal plasma concentrations of estradiol and oxytocin, which were of similar magnitude to those measured in spontaneous term labor. The increase in maternal estradiol preceded the increase in maternal oxytocin levels and myometrial contractions. The onset of the increase in maternal plasma oxytocin was closely associated with the appearance of myometrial contractions after delta4-androstenedione treatment. In contrast, no sustained premature contractions or changes in estradiol and oxytocin occurred in intralipid-treated monkeys. CONCLUSIONS: We conclude that in the 0.8 gestation rhesus monkey (1) the increase in maternal plasma estradiol precedes the increase in maternal plasma oxytocin after delta4-androstenedione treatment and (2) delta4-androstenedione-induced preterm myometrial contractions are closely associated in time with physiologic increases in maternal plasma oxytocin concentrations.

Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey.

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.

Radiologic manifestations of pulmonary tuberculosis.

In summary, the following points are reemphasized: 1. The chest film is the mainstay in the radiologic evaluation of suspected or proven pulmonary TB. CT is occasionally useful for clarifying confusing findings but has not been conclusively shown to have a significant impact on patient management. 2. Primary TB is increasingly a disease of adults. 3. Primary TB usually manifests as a parenchymal consolidation in any pulmonary lobe or segment. Distinguishing features from typical bacterial pneumonia include associated adenopathy, lack of systemic toxicity, failure to respond to conventional antibacterial therapy, and recent PPD conversion. 4. Associated ipsilateral hilar and/or mediastinal adenopathy is almost universal in children with primary TB but is less common in adults. Adenopathy without parenchymal disease is an unusual but well-reported manifestation. 5. Many of the so-called unusual manifestations of adult TB are the usual manifestations of primary disease. The terms adult and childhood TB should be discarded. 6. Postprimary TB typically manifests as a heterogeneous, often cavitary opacity in the apical and posterior segments of the upper lobes and the superior segments of the lower lobes. Lymphadenopathy is rare. 7. Activity of postprimary disease cannot be accurately assessed by chest radiography. Radiographic stability for 6 months and negative sputum cultures is the best indicator of inactive disease. The descriptive terms inactive or old TB should be discarded in favor of radiographically stable TB, as viable bacilli may persist despite adequate therapy. 8. Cavitation is the most important radiologic finding in postprimary disease. Cavitation implies a high bacillary burden, high infectivity, and is associated with numerous complications including endobronchial spread, tuberculous empyema, hematogenous dissemination, pulmonary artery pseudoaneurysm, and so forth. 9. Tuberculous pleurisy is more common in primary than postprimary disease. It is a common presenting manifestation in young adults. The effusions are unilateral, large, and self-limited. The pleural fluid usually is a serous exudate with a marked lymphocytosis. Fluid cultures are frequently negative. Correct diagnosis and therapy is important, as untreated patients are at high risk for subsequent pulmonary reactivation. 10. Miliary disease is also more common in primary than postprimary disease; however, its frequency in elderly patients with postprimary TB is increasing. This form, known as late generalized TB, is apt to be misdiagnosed or not diagnosed in life and has a high mortality.

Regulation of the switch from myometrial contractures to contractions in late pregnancy: studies in the pregnant sheep and monkey.

Myometrial contractility occurs throughout pregnancy and characteristic patterns of myometrial activity exist according to the endocrine status and the relationship to parturition. These characteristic patterns differ between species, yet certain common features can be observed. Throughout pregnancy, myometrial activity is of the contractures type, long-lasting, low-amplitude epochs of activity switching to contraction-type activity at term. This switch from contractures to contractions tends to occur at night and is related to alteration in maternal plasma oestrogen concentrations, and maternal oxytocin function. Studies in several animal species support the hypothesis that maternal oestrogen prepares the myometrium for a periodic signal that causes the switch from contractures to contractions. Several lines of evidence implicate oxytocin in the switch. These studies show that the detailed preparation for parturition takes longer than previously considered and is brought about by a carefully regulated sequence of events in which oestrogen production by the placenta plays a central role.