Calretinin expression as a critical component in the control of dentate gyrus long-term potentiation induction in mice

We have recently reported that mice homozygous (Cr-/-) for a null mutation in the calretinin gene have impaired long-term potentiation (LTP) induction in the dentate gyrus (S. Schurmans et al. (1997) Proc. Natl. Acad. Sci. USA, 94, 10415 ). Here, we investigated dentate LTP induction in mice heterozygous (Cr+/-) for the same mutation. Despite the presence of calretinin in neurons of these mice, although at reduced levels as compared with normal mice, LTP induction in dentate gyrus was totally impaired. Spatial memory and learning were found unaffected in Cr+/- mice, such as in Cr-/- mice. Altogether, our results suggest that calretinin is a critical component in the control of dentate synaptic plasticity in mice, and that levels of calretinin higher than those observed in Cr+/- mice are required to induce LTP in this area. The possible mechanisms leading to the absence of correlation between gene dosage and biological effects are discussed.     

Palliative treatment of wrist joint metastasis of primary bronchial carcinoma with a dynamic compression plate

The authors describe a patient with a wrist metastasis of a primary pulmonary carcinoma. Palliative radiotherapy in combination with splinting failed to release the pain. He was then successfully treated by radiocarpal bridging with a dynamic condylar plate.     

Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis

Over 50% of patients with the polycystic ovary syndrome (PCOS) demonstrate excess levels of adrenal androgens (AAs), particularly dehydroepiandrosterone sulfate (DHS). Nonetheless, the mechanism for the AA excess remains unclear. It has been noted that in PCOS the pituitary and ovarian responses to their respective trophic factors (i.e. GnRH and LH, respectively) are exaggerated. Similarly, we have postulated that excess AAs in PCOS arises from dysfunction of the hypothalamic-pituitary-adrenal axis, due to 1) exaggerated pituitary secretion of ACTH in response to hypothalamic CRH, 2) excess sensitivity/responsivity of AAs to ACTH stimulation, or 3) both. To test this hypothesis we studied 12 PCOS patients with AA excess (HI-DHS; DHS, > 8.1 mumol/L or 3000 ng/mL), 12 PCOS patients without AA excess (LO-DHS; DHS, < 7.5 mumol/L or 2750 ng/mL), and 11 controls (normal subjects). Each subject underwent an acute 90-min ovine CRH stimulation test (1 microgram/kg) and an 8-h incremental i.v. stimulation with ACTH-(1-24) at doses ranging from 20-2880 ng/1.5 m2.h) with a final bolus of 0.25 mg. All patient groups had similar mean body mass indexes and ages, and both tests were performed in the morning during the follicular phase (days 3-10) of the same menstrual cycle, separated by 48-96 h. During the acute ovine CRH stimulation test, no significant differences in the net maximal response (i.e. change from baseline to peak level) for ACTH, dehydroepiandrosterone (DHA), androstenedione (A4), or cortisol (F) or for the DHA/ACTH, A4/ACTH, or F/ACTH ratios was observed. Nonetheless, the net response of DHA/F and the areas under the curve (AUCs) for DHA and DHA/F indicated a greater response for HI-DHS vs. LO-DHS or normal subjects. The AUC for A4 and A4/F and the delta A4/delta F ratio (delta = net maximum change) indicated that HI-DHS and LO-DHS had similar responses, which were greater than that of the normal subjects, although the difference between LO-DHS patients and normal subjects reached significance only for the AUC of the A4 response. No difference in the sensitivity (i.e. threshold or minimal stimulatory dose) to ACTH was noted between the groups for any of the steroids measured. Nonetheless, the average dose of ACTH-(1-24) required for a threshold response was higher for DHA than for F and A4 in all groups. No difference in mean responsivity (slope of response to incremental ACTH stimulation) was observed for DHA and F between study groups, whereas the responsivity of A4 was higher in HI-DHS patients than in normal or LO-DHS women. The net maximal and the overall (i.e. AUC) responses of DHA were greater for HI-DHS than for normal or LO-DHS women. The response of A4 and the delta A4/delta F ratio were greater for HI-DHS patients than for LO-DHS patients or normal subjects. Alternatively, HI-DHS and LO-DHS patients had similar overall responses (i.e. AUC) for A4 or A4/F, although both were greater than those of normal subjects. The relative differences in response to incremental ACTH stimulation between steroids was consistent for all subject groups studied, i.e. A4 > F or DHA. In conclusion, our data suggest that AA excess in PCOS patients is related to an exaggerated secretory response of the adrenal cortex for DHA and A4, but not to an altered pituitary responsivity to CRH or to increased sensitivity of these AAs to ACTH stimulation. Whether the increased responsivity to ACTH for these steroids is secondary to increased zonae reticularis mass or to differences in P450c17 alpha activity, particularly of the delta 4 pathway, remains to be determined.     

Thermal tolerance reduces hyperthermia-induced disruption of working memory: a role for endogenous opiates?

Previous reports indicate that microwave-induced hyperthermia can impair learning and memory. Here, we report that preexposure to a single 20-min period of hyperthermia can produce thermal tolerance and, thereby, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation and reactions to microwave exposure, we also determined how opioid receptor antagonism might modulate these effects. In an initial experiment, rats were exposed daily, over 5 successive days, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions following microwave exposure were prominent after a single previous exposure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/sham-radiation treatment, rats received either saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in contact with new environmental components and less time with familiar objects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia which was significantly lower (on Day 2) in rats receiving repeated treatments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited significantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a distinct preference for the new object whereas the nontolerant animals did not. Naltrexone (10 mg/kg) antagonized the hyperthermia-induced disruption of the object discrimination task (in nontolerant rats) and produced patterns of object exploration that were similar to those of sham-irradiated and thermal-tolerant rats, suggesting that endogenous opioids play a role in the organism's response to heating. Taken together, these data are consistent with the conclusions that 1) microwave-induced hyperthermia can cause a dose-dependent disruption of the normal discrimination between new and familiar objects, 2) physiological reactions to a single hyperthermic episode can produce a thermotolerance that expresses itself in both reduced levels of hyperthermia and attenuated behavioral disruptions following microwave exposure, and 3) opioid antagonism can partially reverse some of the behavioral effects of microwave-induced hyperthermia.     

External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts

A consensus process was undertaken to describe and evaluate current information and practice regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs) and their sex partners. This process developed a number of key statements that were based on strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of men with EGWs are at increased risk for human papillomavirus-related cervical disease and, like all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and general information about sexual health and other sexually transmitted diseases.     

Training decreases muscle glycogen turnover during exercise

Bioelectric activity of a nervous tissue and its synchronization with formatting epileptiform bursts are simulated by a coupled map lattice. The functional units of the map located in the lattice sites represent neural masses which consist of current sources and sinks. The sources lead to depolarization of neurons, and sinks provide hyperpolarization. The map describes a single variable--the bioelectric potential. This potential is created by the interplay of all current sources and sinks in the neural masses. The neural masses are diffusively coupled with each other both by electronic influence and synaptic coupling. Both mechanisms mentioned are suggested to be essential for the formation of synchronous bursts. The transition from chaotic activity to bursts was studied.     

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps

BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.     

ANP gene expression in rat hearts during hypoxia

The relationships between muscle capillarization, estimated O2 diffusion distance from capillary to mitochondria, and O2 uptake (VO2) kinetics were studied in 11 young (mean age, 25.9 yr) and 9 old (mean age, 66.0 yr) adults. VO2 kinetics were determined by calculating the time constants (tau) for the phase 2 VO2 adjustment to and recovery from the average of 12 repeats of a 6-min, moderate-intensity plantar flexion exercise. Muscle capillarization was determined from cross sections of biopsy material taken from lateral gastrocnemius. Young and old groups had similar VO2 kinetics (tau VO2-on = 44 vs. 48 s; tau VO2-off = 33 vs. 44 s, for young and old, respectively), muscle capillarization, and estimated O2 diffusion distances. Muscle capillarization, expressed as capillary density or average number of capillary contacts per fiber/average fiber area, and the estimates of diffusion distance were significantly correlated to VO2-off kinetics in the young (r = -0.68 to -0.83; P < 0.05). We conclude that 1) capillarization and VO2 kinetics during exercise of a muscle group accustomed to everyday activity (e.g., walking) are well maintained in old individuals, and 2) in the young, recovery of VO2 after exercise is faster, with a greater capillary supply over a given muscle fiber area or shorter O2 diffusion distances.     

Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Evidence of the importance of prepreservation injury

We examined platelet adhesion in thirty human donor livers to determine if the degree of platelet adhesion could predict outcome of transplantation. Wedge liver biopsies were taken at the start of the donor operation (biopsy 1) and 1 hr after reperfusion in the recipient (biopsy 2). Biopsies were stained with a monoclonal antibody against platelet glycoprotein Ib and graded for platelet adhesion. Hematoxylin and eosin-stained sections were examined for polymorphonuclear leukocyte adhesion and necrosis. Platelet adhesion was much more frequent and extensive than expected in biopsy 1. Nine of 30 biopsies showed moderate or high-grade platelet adhesion. Thus in this study endothelial cell damage was present in about one-third of donors before the donor operation. The injury was not detectable by routine microscopic or clinical examination or biochemical tests. The degree of platelet adhesion in biopsy 1 predicted development of PMN adhesion and necrosis in biopsy 2 and postoperative transaminase concentrations and prothrombin times in recipients. During preservation and implantation some livers converted from low to either moderate or high grades of platelet adhesion. The grade of platelet adhesion in biopsy 2 predicted postoperative outcome as measured by transaminase and PT levels. Patients whose platelet grade converted to a higher level during preservation and implantation did not do as well as patients who remained at a low adhesion grade. These findings strongly suggest that the degree of platelet adhesion is an important determinant in assessing outcome and may provide a means of measuring the status of liver allografts prior to transplantation.