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Biomedical subjects

A D Mayer

Publications and source records attributed to A D Mayer.

At least 109 records · Page 6Linked to original sources

Prolonged estrogen-progesterone treatment of nonpregnant ovariectomized rats: factors stimulating home-cage and maternal aggression and short-latency maternal behavior.

A 16-day treatment of nonpregnant, ovariectomized rats using 5-mm Silastic implants of estradiol (E), daily injections of 4 mg of progesterone (P), and terminal injections of 5 micrograms/kg of estradiol benzoate (EB) to provide a pregnancy-like pattern of hormone exposure, stimulates (a) home-cage aggression toward unfamiliar intruder rats, (b) short-latency maternal behavior when the females are exposed continuously to pups, and (c) maternal aggression after maternal care has been initiated. Preliminary experiments examined the persistence of stimulation of aggression by the 16-day treatment in the absence of exposure to pups eliciting maternal care, and whether an abbreviated, 1-week treatment stimulates aggression equally. Subsequent experiments examined the importance of the elements of the treatment (E implants, P injections, EB injection), and whether prolonging exposure to P or E would alter its behavioral effects. The full 16-day E/P/EB treatment stimulated higher levels of home-cage and maternal aggression, and shorter maternal behavior latencies than abbreviated and partial treatments. E in combination with P or EB significantly raised home-cage aggression, whereas P alone was without effect. Administering P for 2 additional days attenuated reductions in maternal behavior latencies by E/P/EB, but did not reduce home-cage or maternal aggressiveness. Continuous exposure to E throughout testing did not affect any dependent variable. Comparing these findings to earlier data and reports suggests that hormone exposure for 2 weeks or more, and provision of P levels approaching those of pregnancy are important to the effects of the E/P/EB treatment on aggression.

Aggression↗

Hormonal basis during pregnancy for the onset of maternal behavior in the rat.

This article reviews the current state of our knowledge about the hormonal basis of maternal behavior in the rat. Considered are the ovarian hormones estrogen and progesterone, the pituitary hormones beta-endorphin and prolactin, and the hormone oxytocin, secreted by several hypothalamic nuclei and associated brain regions. The hormones of pregnancy, estrogen and progesterone, prime the female to respond to a terminal rise in estrogen that stimulates a high level of maternal responsiveness even before parturition begins. Studies on the role of prolactin, using hypophysectomy, prolactin release blockers and anterior pituitary and prolactin replacement, indicate that prolactin is required for the ovarian hormones to be effective in stimulating maternal behavior. During the latter half of pregnancy, placental lactogen may displace prolactin in this role. Although prolactin serves as a chronic stimulus for maternal behavior, it also may act over a short period. Oxytocin stimulates maternal behavior in a specific strain of rat, but not in other strains, and only when administered introcerebroventricularly (ICV) in estrogen-primed females. The decline in the high brain levels of beta-endorphin around parturition has been proposed as a requirement for the onset of maternal behavior; morphine blocks the onset of maternal behavior and disrupts ongoing maternal behavior and maternal aggression in lactating females. However, blocking beta-endorphin action at parturition interferes with pup cleaning and eating of the placenta as well.

Animals↗

Intra-peritoneal aprotinin therapy for acute pancreatitis. Preliminary pharmacodynamic studies.

In acute pancreatitis a toxic exudate accumulates within the peritoneal cavity, which contains activated pancreatic proteinases. Peritoneal lavage removes the exudate effectively, washing it away with large volumes of saline solution, but is of unproven therapeutic value and may have deleterious effects. These may be avoided by combining lower volume peritoneal washouts with intra-peritoneal installation of a proteinase inhibitor, although therapeutic effectiveness may be compromised by systemic absorption depending on the inhibitor selected. This latter effect was studied in fifteen patients with acute pancreatitis, treated by simple peritoneal washout and bolus intra-peritoneal administration of aprotinin (Trasylol) solution.

Absorption↗

Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology.

The levels of pancreatic digestive enzymes, lysosomal hydrolases, and protease inhibitors were evaluated in ascites fluid from 24 patients with acute pancreatitis diagnosed as alcoholic, gallstone-induced, or idiopathic. In this group the concentrations of amylase (354 +/- 98 ng/ml), immunoreactive cationic trypsinogen (1840 +/- 238 ng/ml), and immunoreactive elastase 2 (1492 +/- 262 ng/ml) were greatly elevated in comparison to the corresponding serum values. Enzyme levels in ascites from the idiopathic pancreatitis group tended to be higher than the levels from the other two groups. Activity of acid phosphatase and beta-glucuronidase was significantly higher in ascites compared to serum in all groups. On the other hand, levels of immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin in ascites fluid were about half the average concentrations reported for normal serum. Significant amounts of tryptic amidase activity (61.7 +/- 13.7 micrograms/ml) were observed, indicating a trypsin-alpha 2-macroglobulin complex. These data indicate an imbalance in the protease-to-inhibitor ratio in ascites fluid from patients with acute pancreatitis. Coupled with elevated ribonuclease activity (27.4 +/- 3.4 units), a positive methemalbumin test in 23 of 24 patients (1.1 +/- 0.4 mg hematin/100 ml), and an average protein concentration of 4.0 +/- 0.2 g/100 ml, these observations demonstrate that abdominal paracentesis and the biochemical analyses of ascites fluid provide useful information related to the biochemical events in acute pancreatitis and may be useful in the diagnosis of difficult cases, but their predictive value of severity remains to be established.

Acute Disease↗

Mammary stimulation and maternal aggression in rodents: thelectomy fails to reduce pre- or postpartum aggression in rats.

In mice, tactile stimulation of the nipples appears to be critical for the onset of postpartum maternal aggression. Surgical removal of the nipples (thelectomy) blocks aggression if performed prior to parturition. In rats, indirect evidence suggests a similar role for nipple stimulation in maternal aggression. Two experiments were undertaken to determine whether thelectomy prior to mating reduces pregnancy-induced and/or postpartum aggression in this species. In the first, thelectomized and sham-thelectomized females were subjected to home cage tests (pups, if any, present) with unfamiliar male intruders on Gestation Days 18 and 21 and Lactation Days 3 and 5. Additional groups of thelectomized females were tested one time only on either Lactation Day 5 or 12. Thelectomized and control females were equally aggressive; postpartum, nearly all females in both groups attacked. Experiment 2 used females that were hysterectomized-ovariectomized (HO) on Gestation Day 16. Such females are not aggressive prior to initiating maternal behavior, but become highly aggressive (over 80% attacking) after commencing maternal care. Females again were thelectomized or sham-thelectomized prior to mating. On Day 16 HO was performed, and 48 hr later continuous exposure to pups was begun. After the females had displayed maternal behavior for 1.5-2 days, intruder tests were conducted. All females attacked at least once, with no differences between treatment groups. Thus thelectomy does not reduce maternal aggression in the rat. This finding, however, does not preclude a role for tactile ventral stimulation in mediating maternal aggression.

Aggression↗

Hormonal factors influence the onset of maternal aggression in laboratory rats.

This experiment addressed the hypothesis that aggressiveness toward conspecifics is stimulated by hormonal factors known to mediate the onset of maternal care. Subjects included both pregnant and virgin females. Sixteen-day pregnant rats were hysterectomized (H), hysterectomized-ovariectomized and injected with estrogen (HO-EB), or subjected to sham procedures. Nonpregnant females were HO-EB or sham operated. The females were sensitized by continuous exposure to pups and were judged to have initiated maternal care when all pups were retrieved and grouped, Aggressiveness was observed during 5-min intruder tests using unfamiliar males, administered (a) 10 min prior to the introduction of test pups, (b) following the first 3 hr of pup exposure, and (c) after females had initiated maternal care. The results revealed that treatments known to reduce sensitization latencies also increased aggressiveness even prior to exposure to pups. Aggressiveness was displayed before sensitization only in groups having elevated estrogen levels. After initiating maternal behavior, pregnant and pregnancy-terminated females increased further in aggressiveness whereas nonpregnant females did not. Pregnancy-terminated, HO-Oil females became aggressive (only) after initiating maternal behavior, indicating that factors other than estrogen also influence the onset of maternal aggression.

Aggression↗

Digestive enzymes and protease inhibitors in plasma from patients with acute pancreatitis.

The plasma levels of certain digestive enzymes and protease inhibitors were determined in 40 patients with severe acute pancreatitis diagnosed as gallstone-induced (GP), alcoholic (AP), or idiopathic (IP). On admission, plasma levels of amylase and immunoreactive cationic trypsin(ogen) (IRCT) and elastase 2 (IRE 2) were found to be 50 +/- 10 ng/ml, 340 +/- 64 ng/ml, and 190 +/- 15 ng/ml, respectively, in all groups of patients. These enzymes levels remained high for the first 2 days following hospitalization and then decreased, although amylase and IRCT levels remained elevated above normal values throughout the study period (2 weeks). In general amylase and IRCT were lower in patients with concomitant ascites, pancreatic pseudocysts, or abscesses, and higher in patients who died, as compared to the pancreatitis group as a whole. In these patients, levels of immunoreactive alpha 1-protease inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) remained relatively constant at the lower end of the normal range throughout the study period. Inhibitor levels in plasma were unaffected by the etiology of pancreatitis or the occurrence of complications. A similar trend was seen with plasma levels of lysosomal hydrolases. The results indicate that in this group of patients, plasma levels of pancreatic digestive enzymes were reflective of the clinical features and severity of the disease, as well as the time following the acute attack that brought the patient to the hospital.

Acute Disease↗

Effects of brain antiestrogen implants on maternal behavior and on postpartum estrus in pregnant rats.

To test the hypothesis that the onset of maternal behavior is stimulated by estrogen, we examined the effects of medial preoptic area (MPOA) or ventromedial hypothalamus (VMH) implants of the antiestrogen 4-hydroxytamoxifen (OH-TAM) on pre- and postpartum maternal behavior and on postpartum estrus in rats. On day 20 of pregnancy, animals were implanted bilaterally with OH-TAM or cholesterol cannulae into MPOA or VMH. Unilateral cannulae of OH-TAM were also placed into MPOA. Females were tested with newborn pups for the onset of immediate retrieval, prepartum, at noon on day 21, at midnight of the day 21, and 1 day following parturition (which occurred on day 22). On the evening of parturition, implanted animals were tested with stimulus males for the occurrence of postpartum estrus. In order to examine the influence of estrogen on maternal behavior in the absence of parturitional experience, antiestrogen-implanted animals were delivered surgically (cesarean section) and were observed for the display of maternal behavior at various times after surgery. At noon of day 21, only a few animals in any group retrieved pups. However, 12 h later, females that received bilateral OH-TAM implants into MPOA remained nonresponsive, while over 80% animals in other groups retrieved and gathered pups. The antiestrogen did not disrupt the display of postpartum maternal behavior in those females that were allowed to undergo normal parturition, but it significantly reduced the number of cesarean-delivered animals showing maternal behavior. Bilateral implants of OH-TAM into VMH, but not into MPOA, effectively blocked postpartum estrus. The MPOA implants of OH-TAM resulted in a significant reduction in cytoplasmic estrogen receptor levels and an increase in nuclear estrogen receptor concentrations. The results of these experiments lend support to the current hypothesis that estrogen acts most effectively in the MPOA to stimulate maternal behavior and in the VMH to facilitate sexual receptivity.

Animals↗

Peritoneal fluid in human acute pancreatitis blocks hepatic mitochondrial respiration.

Peritoneal fluid may be the source of multi-system failure during the initial stages of acute pancreatitis. The toxicity of human pancreatic ascitic fluid (HPAF) collected under sterile conditions from 12 patients with acute pancreatitis was investigated with the use of an in vitro preparation of mitochondria. Hepatocyte mitochondria from Sprague-Dawley rats were prepared by standard techniques. Mitochondrial oxidative activity was determined in glutamate-malate medium, with micromodification of the YSI Model 53 (Yellow Springs, Ohio) oxygen electrode system. The oxygen uptake of 150 to 200 microliter samples of mitochondria suspension (20 to 25 mg/ml) was monitored for 3 minutes, after which 3 microliter of 0.1 M adenosine diphosphate (ADP) was added to the chamber to induce state 3 respiration. Two minutes after the oxygen trace returned to state 4 respirations, 20, 40, or 80 microliter of the HPAF sample was introduced into the reaction vessel and the oxygen measurement continued for an additional 3 minutes. After this, 3 microliter of 0.1 M ADP again was added to the reaction chamber and the oxygen measurement continued. Control runs were made with reconstituted pooled human serum used in place of the HPAF samples. A significant (p less than 0.05) increase in state 4 respiration occurred in all 12 samples of HPAF. Addition of ADP showed a significant decline (p less than 0.05) in respiratory control ratio in all specimens. A dose-response curve was observed in 8 of 12 HPAF samples tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Prediction of severity in acute pancreatitis: prospective comparison of three prognostic indices.

The prognostic value of three predictive indices was compared in 436 attacks of acute pancreatitis in 418 patients. The outcome of an attack was graded as uncomplicated (324), complicated (70), or fatal (41); 1 attack was excluded because of puncture of the caecum. The overall mortality rate was 9.4%. Clinical assessment on admission identified only 34% of patients whose attack was severe (ie, complicated or fatal). Multiple laboratory criteria and peritoneal lavage were more sensitive (61% and 53%, respectively) while retaining diagnostic accuracy (79% and 74%). An erroneous diagnosis of pancreatitis was corrected by the findings on lavage in 5 patients. The major advantage of peritoneal lavage over multiple laboratory criteria was the shorter delay between admission to the study and determination of severity (median 4 v 24 h), but visceral puncture during insertion of the cannula occurred in 2 of 253 patients (0.8%). When used together, the three indices correctly predicted 82% of the attacks with a severe outcome and identified all patients destined to die within 10 days of admission.

Acute Disease↗

Controlled clinical trial of peritoneal lavage for the treatment of severe acute pancreatitis.

We performed a multicenter, randomized, controlled clinical trial of therapeutic peritoneal lavage (2 liters per hour for three days) in 91 patients with severe acute pancreatitis. Patients were entered into the study if severe pancreatitis was indicated by multiple laboratory criteria or diagnostic peritoneal lavage. All patients received full supportive treatment. The median time between the onset of symptoms and randomization was 38 hours. Forty-six patients were assigned to the control group and 45 to the lavage group. There were 13 deaths (28 per cent) and 16 patients with major complications (35 per cent) in the control group, as compared with 12 deaths (27 per cent) and 17 patients with major complications (38 per cent) in the lavage group. Lavage did not appear to modify the length of survival, the incidence of pancreatic collections (pseudocysts or abscesses), or the plasma amylase concentration. Considering the statistical power of the design, we conclude that the outcome of severe pancreatitis was not greatly, if at all, influenced by the regimen of peritoneal lavage used in this study.

Acute Disease↗

Screening for acute pancreatitis: a rapid assay for plasma lipase.

A simple agglutination test for plasma immunoreactive lipase has been evaluated in 101 patients. A positive agglutination reaction was observed if, and only if, plasma lipase exceeded 300 micrograms/l. The test was positive in all 23 patients with acute pancreatitis who were tested on the day of admission to hospital, in one patient with a pancreatitic pseudocyst and in one patient with hyperamylasaemia and hyperlipasaemia due to a perforated duodenal ulcer. The simplicity and reliability of this test make it suitable as an urgent diagnostic investigation for acute pancreatitis.

Acute Disease↗

Opiate antagonism reduces placentophagia and pup cleaning by parturient rats.

Since endogenous opiate mechanisms are activated during parturition, the present study examined in rats the effects of opiate antagonism on maternal care during and shortly after parturition. Endogenous opiate mechanisms were blocked in late pregnant rats by (1) naltrexone pellet implants (Experiment 1); (2) acute naloxone injections of 10 mg/kg (Experiment 2) or 0.1 mg/kg (Experiment 7); or (3) induction of opiate tolerance (Experiment 3). All methods resulted in a significant decrease in placentophagia and/or in cleaning pups of umbilical cords and birth fluids (Experiment 6). Other aspects of maternal care appeared relatively unaffected and 24 hr pup survival rats were lowered only by induction of morphine tolerance (probably via its effects on the young). In nonpregnant females, naloxone produced a small but significant decrease in placentophagia (Experiment 4) whereas morphine-tolerant nonpregnant females consumed placentas as readily as controls (Experiment 5). Thus the inhibition of placentophagia produced by opiate antagonism may be specific to conditions associated with parturition. These findings suggest that endogenous opiates support placenta eating and pup cleaning during and immediately after birth. Mediation may be via opiate effects on ingestive behavior, and/or via a reduction in the stress of parturition which otherwise can interfere with the female's ability to perform these tasks.

Animals↗

Enzyme transfer from pancreas to plasma during acute pancreatitis. The contribution of ascitic fluid and lymphatic drainage of the pancreas.

Acute pancreatitis was induced in anaesthetised dogs in order to investigate the relative contribution of peritoneal ascitic fluid and thoracic duct lymph as routes of transfer of pancreatic enzymes from the inflamed gland to the blood. In eight animals the exudate from the gland was collected in a plastic bag and continuously drained away, and in a further eight it was allowed to accumulate within the peritoneal cavity. The thoracic duct was cannulated and in four of the animals of each group the lymph which drained was discarded; in the other four it was returned via a venous cannula. The initial rise of plasma amylase and lipase was probably because of the direct transfer of enzyme into veins draining the pancreas or peri-pancreatic tissues. Thereafter transfer of enzyme via the thoracic duct significantly influenced plasma concentrations of amylase and lipase. The majority of enzyme released from the gland accumulated within the peritoneal ascitic fluid, but this intraperitoneal accumulation did not appear to have a significant influence upon lymph or plasma concentrations of amylase or lipase.

Acute Disease↗

A comparative study of adsorbed tetanus vaccine.

A study is reported in which 197 volunteers were given adsorbed tetanus vaccine from two different sources. Using an ELISA system all pre-vaccination sera were screened. Both pre- and post-vaccination sera from volunteers with an initial antibody level of less than 1 iu/ml were then titrated and the antibody response analyzed. The results confirm that both vaccines produced an excellent antibody response with little difference in reactogenicity.

Adsorption↗

Biochemical identification of patients with gallstones associated with acute pancreatitis on the day of admission to hospital.

Current trends in the treatment of gallstone pancreatitis require rapid diagnosis of cholelithiasis. This study evaluates the diagnostic potential of plasma aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin on the day of admission to hospital in 215 attacks of acute pancreatitis. The optimal diagnostic cut-off level for AST was 60 IU/1. A transient elevation above 60 IU/1 was recorded in 111 (84.1%) of 132 attacks associated with gallstones, but in only 12 (14.5%) of 83 attacks without stones, and was unrelated to the severity of the attack. Elevated levels of alkaline phosphatase and bilirubin were also more common in attacks associated with gallstones but were less reliable for the identification of cholelithiasis than AST. As a sensitive indicator of hepatocyte disruption, the early and transient rise in plasma AST is consistent with the concept of transient ampullary obstruction in gallstone pancreatitis, and may be useful in identifying patients who require urgent surgical or endoscopic disimpaction.

Acute Disease↗