Use of end-tidalPco 2 and transcutaneousPco 2 as noninvasive measurement of arterialPco 2 in extubated patients recovering from general anesthesia

This study was designed to assess the accuracy of end-tidalPco ₂ and transcutaneousPco ₂ as measurements of arterialPco ₂ in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidalPco ₂ were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. ArterialPco ₂ values were corrected for body temperature. Values for Paco ₂ were compared with those forPetCO₂ and Psco ₂ by linear regression analysis and by calculation of bias ± precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterialPco ₂ regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterialPco ₂. Although the measurements of bias and precision of noninvasivePco ₂ monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use ofPetCO₂ or Psco ₂ for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia.     

Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease.

Our earlier studies using the Consortium to Establish a Registry of Alzheimer's Disease neuropsychological battery showed that delayed recall was a highly sensitive indicator of early Alzheimer's disease. None of the learning and memory measures in the battery were found to be useful in staging the severity of this form of dementia. This study explores the nonmemory functions (fluency, naming, and praxis) of the Consortium to Establish a Registry of Alzheimer's Disease battery and asks whether performance on any of these measures adds to the detection of early Alzheimer's disease or is sensitive to the later progression of the illness. We stratified patients with this disease according to severity (mild, moderate, severe), and compared them with age-, education-, and gender-matched control subjects (group N = 49 each). Multivariate procedures and cutting scores were used to determine the efficacy of the various measures in distinguishing between the cases and control subjects. Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease. Confrontation naming was the only nonmemory factor that assisted in this discrimination. For staging the illness, a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease. Measures of delayed recall quickly "bottomed out" in the patients with Alzheimer's disease and proved of little value in staging the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumor Vascularity Is Not a Prognostic Factor for Malignant Melanoma of the Skin

Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most suitable vascular marker for this study. Our results indicate that there was no statistically significant difference between the two groups with regard to tumor vascularity. Even after identifying 15 cases of thin (<1.0 mm thick) melanoma, there was no significant difference in the number of microvessels between metastasizing and non-metastasizing tumors. Comparison of patterns of vascular microarchitecture also failed to discriminate between the two groups. Thus, our results indicate that tumor vascularity may not be an independent prognostic factor for cutaneous melanoma.     

Horseradish peroxidase transport across rabbit jejunum and Peyer's patches in vitro

Uptake and transport of horseradish peroxidase (HRP) have been observed in both Peyer's patches (PP) and jejunal epithelium (JE), and the quantities transported across each tissue were compared. Steady-state was reached much faster in PP than in JE. In Ringer solution, no significant difference was found between the HRP fluxes conveyed through PP and JE. In the presence of 10 mM glucose, slight net secretion was observed in JE but not in PP. In both tissues, the transport mechanism was shown to be sensitive to metabolic inhibitors. By contrast, in PP, ammonia did not significantly enhance intact HRP fluxes. Intracellular transfer and catabolism were estimated by measuring transepithelial fluxes of tritiated HRP. In PP, fluxes from mucosa to serosa and from serosa to mucosa were both greatly reduced (9.18 +/- 3.9 and 10.5 +/- 5.1 pmol X h-1 X cm-2, respectively) compared with JE (106.02 +/- 16 and 31.3 +/- 9.3). These results indicate that intact HRP fluxes are similar in PP and JE, but that tritiated HRP fluxes (intact plus degraded HRP fluxes) are smaller in PP. Together, these results suggest that the specific characteristics of HRP transport across PP are fast uptake and reduced degradation.     

Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Viewpoint: suggestions for a shift in teaching clinical skills to medical students: the reflective clinical examination.

How medical students are taught physical examination (PE) skills appears to have changed little since the 1950s. Textbooks are organized according to organ systems and describe methods of eliciting and recording history and PE data using a routine format. In many medical schools, the preclinical teaching programs for clinical examination skills similarly emphasize an orderly collection of data. Teaching students to use diagnostic reasoning is postponed until students have learned history-taking and PE skills. The authors propose three modifications to this educational approach. First, rather than performing the clinical examination using a routine format, students should be encouraged to form diagnostic hypotheses early on while listening to the patient's narrative, and conduct the subsequent search for history and PE data in a reflective way in order to confirm or refute these hypotheses. Second, the authors propose that interviewing patients and conducting the PE be taught by one-on-one tutoring until students achieve mastery. Last, they suggest that the PE be guided not only by students' diagnostic hypotheses, but also by patients' expectations. These modifications are consistent with current trends in medical education that encourage a reflective practice and problem-based learning (PBL), and they also introduce medical students to the precepts of clinical reasoning. The authors suggest that challenging students to seek specific physical findings may increase the likelihood of detecting findings when they are present, and may transform patient interviewing and conducting the PE from routine activities into intellectually exciting experiences.     

Spatial and temporal dynamics of Puumala hantavirus infection in red bank vole (Clethrionomys glareolus) populations in Belgium

Dynamics of hantavirus infection and population densities in rodents were investigated from 1996 to 1999 in southern Belgium. Evidence of Puumala infection was restricted to Clethrionomys glareolus. Although the serotype was not determined, antibodies against hantavirus were also found in eight Apodemus sylvaticus. In fall 1996, the seroprevalence in C. glareolus was high (20.1%, 37 of 184) and the infection was widely distributed in the area studied whereas a focal occurrence of positive rodents and lower seroprevalence rates were recorded in spring 1997 (14.3%, six of 42), fall 1997 (6. 6%, 11 of 166), spring 1998 (6.4%, three of 47) and fall 1998 (6.7%, 11 of 165). A pullulation of rodents was observed in spring 1999 and was associated with a markedly higher seroprevalence in C. glareolus (47.7%, 189 of 396). In all seasons, infection rates in adults were higher than in juveniles and subadults. No significant difference of prevalence was recorded between males and females. In two trapping sites, the temporary disappearance of positive animals after a crash in rodent populations suggests that a threshold in density is necessary for the maintenance of the enzootic cycle.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.