Differential distribution of metabotropic glutamate receptors 1a, 1b, and 5 in the rat spinal cord

Metabotropic glutamate receptors (mGluRs) modulate somatosensory, autonomic, and motor functions at spinal levels. mGluR postsynaptic actions over spinal neurons display the pharmacologic characteristics of type I mGluRs; however, the spinal distribution of type I mGluR isoforms remains poorly defined. In this study, the authors describe a differential distribution of immunoreactivity to various type I mGluR isoforms (mGluR1a, mGluR5a,b, and mGluR1b) that suggests a correlation between specific isoforms and particular aspects of spinal cord function. Two different antisera raised against mGluR5a,b detected intense immunoreactivity within nociceptive afferent terminal fields (laminae I and II) and also in autonomic regions (parasympathetic and sympathetic). In contrast, two of three anti-mGluR1a antibodies did not immunostain lamina I or II. Laminae I and II immunostaining by a third anti-mGluR1a antibody was competed by a peptide sequence obtained from a homologous region in mGluR5, suggesting possible cross reactivity in fixed tissue. Autonomic neurons did not express mGluR1a immunoreactivity. All anti-mGluR1a antibodies strongly and specifically immunolabeled dendritic and somatic membranes of neurons in the deep dorsal horn (lamina III-V) and the ventral horn (lamina VI-IX). Somatic motoneurons expressed mGluR1a immunoreactivity but little or no mGluR5 immunoreactivity. Phrenic and pudendal motoneurons expressed the highest level of mGluR1a immunoreactivity in the spinal cord. Intense mGluR1b immunoreactivity was restricted to a few scattered neurons and a prominent group of neurons in lamina X. Lamina II neurons expressed low levels of mGluR1b immunoreactivity. Ultrastructurally, type I mGluR immunoreactivity was found mostly at extrasynaptic sites on the plasma membrane, but it was also found perisynaptically, in the body of the postsynaptic regions or in relation to intracytoplasmic structures.     

Reserve nitrous oxide cylinders on anaesthetic machines. A survey of attitudes and equipment at a large DGH

The presence of reserve nitrous oxide cylinders on anaesthetic machines is not necessary and potentially hazardous, wasteful and polluting. Although reserve nitrous oxide cylinders are routinely present on the anaesthetic machines in many hospitals in the UK, it is our concern that they are not checked or maintained properly. We examined a sample of cylinders and surveyed the practice amongst the anaesthetic staff in our Department with an anonymous questionnaire. This confirmed that: (1) the equipment is not properly maintained, 68% of cylinders sampled having passed a 3-year expiry date; (2) checks are of little practical use, are not routinely performed by anaesthetists, and only 46% of respondents routinely check the nitrous oxide cylinders. In conclusion, the nitrous oxide cylinders are not properly checked or maintained and may represent a safety hazard.     

Are obstetric risk factors and bowel symptoms associated with defaecographic and manometric abnormalities in women awaiting hysterectomy?

Abdominal hysterectomy has been shown to affect anorectal function. These studies are either population-based or have been performed retrospectively. It is not clear from the literature whether those subjects awaiting hysterectomy already have an element of pelvic floor failure and which may be related to obstetric risk factors. A complete anorectal assessment was performed in a group of women awaiting hysterectomy who did not volunteer any bowel symptoms. The patients studied were part of an ongoing study of the functional effects of abdominal hysterectomy. All had their anorectal function assessed before their respective surgery by a questionnaire (functional bowel score), Cleveland continence score, endoanal ultrasound (U/S), anal manometry, defaecatory proctogram and colonic transit. A detailed obstetric history, which included risk factors such as parity, type of delivery, duration of labour and elevated birth weight, were also recorded. Patients with previous bowel disease, bowel surgery and anal sphincter repair were excluded. There were 39 subjects with a median age of 43 years (range 31-65), respectively. Thirty-three rectocoeles and 22 intussusceptions were demonstrated. Two had poor puborectalis function, while five had cough incontinence. Two women had abnormal colonic transit. Thirteen had abnormal anal manometry. Endoanal ultrasound was normal in all patients. None of the obstetric risk factors were associated with rectocoele, intussusception or abnormal anal manometry. Low squeeze pressure was associated significantly with more bowel symptoms (P=0.03). However, rectocoele, intussusception, abnormal colonic transit, abnormal resting anal pressure and maximal tolerated volume were not statistically significantly associated with bowel symptoms. The majority of female subjects who were awaiting hysterectomy had physiological and proctographic abnormalities consistent with pelvic floor failure. Obstetric risk factors were not associated with rectocoele, intussusception, abnormal colonic transit and anal manometry in this cohort of patients. Similarly, the majority of proctographic abnormalities were not associated with bowel symptoms. However, a trend was noted associating bowel symptoms with manometric abnormalities.     

The association of HER-2/neu amplification with breast cancer recurrence

HYPOTHESIS: Amplification of the HER-2/neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival. DESIGN: Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/neu testing. The mean follow-up was 56 months. SETTING: Large, urban, tertiary care hospital. PATIENTS: From 1995 to 1999, a consecutive sample of 190 patients with breast cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncogene by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but received their treatment elsewhere. All patients tested for HER-2/neu after diagnosis with breast cancer in 1999 (n = 47) were excluded from analysis because of short follow-up time. One patient was excluded who had in situ ductal carcinoma. The remaining 93 patients were analyzed. RESULTS: Of 93 patients, 40 (43%) had gene amplification. Overall, patients with oncogene amplification had a shorter median disease-free interval (22 months) compared with controls (40 months) (P =.003). Analysis by the Cox regression model showed that the HER-2/neu status remained significantly associated with time to relapse even after adjusting for age and tumor grade (P =.002; adjusted relative risk, 2.4; 95% confidence interval, 1.4-4.4). No association was found between gene amplification and tumor grade (P =.98), estrogen/progesterone receptor status (P = .29 and P = .43, respectively), or lymph node status (P = .98). Seventy-two patients (77%) eventually had disease recurrence, with 18 (25%) of these recurring locally. CONCLUSIONS: The HER-2/neu oncogene is an independent prognostic indicator of a subset of breast cancers that are at high risk of early recurrence, regardless of tumor grade, estrogen/progesterone receptor status, and lymph node status. Patients amplifying the HER-2/neu oncogene have a shorter disease-free survival than patients without the oncogene.     

Evaluation of subsecond gated helical CT for quantification of coronary artery calcium and comparison with electron beam CT

OBJECTIVE: Since its introduction early in the 1990s, helical CT has become the predominant technology for obtaining CT images for medical applications. Recent improvements in the temporal resolution of helical CT (subsecond) and the addition of retrospective cardiac gating are combined in this report evaluating cardiac-gated helical CT for quantifying coronary artery calcium. We compare total calcium scores determined on subsecond gated helical CT with the current reference for coronary calcium evaluation, electron beam CT. MATERIALS AND METHODS: We compared total calcium scores obtained using a general purpose, unmodified helical CT scanner with scores obtained using electron beam CT in 36 individuals who were 68+/-11 years old (age range, 41-85 years). RESULTS: Correlation coefficients ranged from 0.97 to 0.98 (Pearson's product moment) and from 0.95 to 0.96 (Spearman's rank order), depending on the coronary calcium scoring method used. Agreement in the classification of participants as "healthy" or "diseased" at threshold total calcium scores of 10, 100, 160, 200, 400, and 680 was, respectively, 94%, 97%, 89%, 92%, 94%, and 100% using the conventional electron beam CT scoring method and an equivalent method with helical CT. CONCLUSION: A general purpose, current generation helical CT scanner equipped for retrospective cardiac gating can accurately quantify coronary calcium, and the results are highly correlated to scores obtained with electron beam CT. As an alternative method for measuring coronary calcium, gated subsecond cardiac helical CT offers greater availability and lower cost, thereby making population-based screening for coronary artery calcium more feasible.     

Individualized norms of optimal fetal growth: fetal growth potential

OBJECTIVE: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods. METHODS: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications. RESULTS: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05). CONCLUSION: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms. LEVEL OF EVIDENCE: II.     

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.