Methane production, rumen fermentation, and diet digestibility of Holstein and Jersey dairy cows being divergent in residual feed intake and fed at 2 forage-to-concentrate ratios.

Improving feed efficiency of dairy cows through breeding is expected to reduce enteric methane production per unit of milk produced. This study examined the effect of 2 forage-to-concentrate ratios on methane production, rumen fermentation, and nutrient digestibility in Holstein and Jersey dairy cows divergent in residual feed intake (RFI). Before experimental onset, RFI was estimated using a random regression model on phenotypic herd data. Ten lactating Holstein and 10 lactating Jersey cows were extracted from the herd and allocated to a high or low pre-experimental RFI group of 5 animals each within breed. Cows were fed ad libitum with total mixed rations either low (LC) or high (HC) in concentrates during 3 periods in a crossover design with a back-cross and staggered approach. Forage-to-concentrate ratio was 68:32 for LC and 39:61 for HC. Cows adapted to the diets in 12 to 24 d and feces were subsequently collected on 2 d. Afterward, gas exchange was measured in respiration chambers and rumen liquid was collected once after cows exited the chambers. Pre-experimental RFI was included in the statistical analysis as a class (low and high RFI) or continuous variable. Methane per kilogram of dry matter intake (DMI) was lower for Holsteins than Jerseys and the response to increased concentrate level was more pronounced for Holsteins than Jerseys (27.2 vs.13.8%); a similar pattern was found for the acetate:propionate ratio. However, methane production per kilogram of energy-corrected milk (ECM) was unaffected by breed. Further, total-tract digestibility of neutral detergent fiber was higher for Jerseys than Holsteins. For RFI as a class variable, DMI, methane production regardless of the expression, and digestibility were unaffected by RFI. For RFI as a continuous variable, DMI was lower and methane per kilogram of DMI was higher for cows with negative (efficient) than positive (inefficient) RFI values, and neutral detergent fiber digestibility was higher for Holsteins with negative than positive RFI values, but not for Jerseys. Daily methane production and methane per kilogram of ECM were unaffected by RFI. In conclusion, methane per kilogram of DMI of Jerseys was lowered to a smaller extent in response to the HC diet than of Holsteins. When pre-experimental RFI was used as a continuous variable, higher methane per kilogram of DMI was found for cows with negative RFI than positive RFI values, but not for methane per kilogram of ECM. These findings call for validation in larger studies.

Expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in serosal tissue of intraperitoneal organs and adhesions.

OBJECTIVE: To compare expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP (TIMP-1) in serosal tissue of intraperitoneal organs and adhesions. DESIGN: Prospective and cross-sectional study. SETTING: Academic research centers. PATIENT(S): Patients undergoing abdominal or pelvic surgery. INTERVENTION(S): MMP-1 and TIMP-1 expression. MAIN OUTCOME MEASURE(S): Expression of messenger ribonucleic acid (mRNA) and protein was measured by using quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. RESULT(S): Serosal tissue of intraperitoneal organs and adhesions express MMP-1 and TIMP-1 mRNA and protein at levels that are consistently varied with 10- to 10,000-fold and 2- to 10-fold higher TIMP, mRNA and protein, respectively. Parietal peritoneum, fallopian tubes and ovaries express higher MMP-1 mRNA levels compared with uterus and adhesions; the lowest expression is found in small and large bowels, subcutaneous tissue. and omentum. Expression of TIMP-1 mRNA was less variable; the highest level was found in the uterus and the lowest in subcutaneous tissue and small bowels. There was less variability in MMP-1 and TIMP-1 protein content than mRNA expression; ovaries and adhesions contained the highest MMP-1 and TIMP-1 levels, respectively, and peritoneum contained the lowest. The MMP-1 and TIMP-1 content and ratios further indicate limited MMP-1 proteolytic activity. Although tissues from premenopausal women express more MMP-1 and TIMP-1, expression did not differ by sex or age. CONCLUSION(S): Because MMP-1 and TIMP-1 expression varies consistently among the serosal tissues of peritoneal organs and adhesions, and because tissue injury alters their expression, site-specific variations in expression of these substances may predispose a particular organ to develop more adhesions.

Differential expression of TGF-beta1 and TGF-beta3 in serosal tissues of human intraperitoneal organs and peritoneal adhesions.

Elevated local expression of transforming growth factor (TGF-beta) has been associated with increased incidence of peritoneal adhesion formation. In this study we determine whether differences in basal expression of TGF-beta in serosal tissue of peritoneal organs correlate with incidence of adhesion formation. Serosal tissue of parietal peritoneum, uterus, oviduct, ovary, omentum, large and small bowels as well as adhesions, skin, fascia, subcutaneous tissue, peritoneal fluid and serum were collected from 57 subjects with/without adhesions who were undergoing abdominal/pelvic surgery. To determine TGF-beta1 and TGF-beta3 mRNA and protein expression, total RNA and protein were isolated from these tissues and along with the fluids, subjected to quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) respectively. Tissue sections were immunostained for TGF-beta1 and TGF-beta3 protein. We found that TGF-beta1 and TGF-beta3 mRNA and protein are expressed in these tissues and present in peritoneal fluids and serum, with considerable variations in level of their expression. Comparatively, there was more variation in TGF-beta1 than TGF-beta3 expression without age or gender relation. Adhesions express a significantly higher TGF-beta1 mRNA and have the highest TGF-beta1:TGF-beta3 ratio, with lowest concentrations and ratio detected in omentum, small and large bowels; in contrast uterus expresses higher TGF-beta3, with lowest concentrations detected in subcutaneous tissue and large bowels (P < 0.05). A similar trend was also observed for total (active + latent) TGF-beta1 protein expression, with low active TGF-beta1 that was not significantly different among the tissue extracts and fluids. However, the lowest active:total TGF-beta1 ratio was found in adhesions and ovary. In subjects with adhesions, the adhesions express significantly more TGF-beta1 compared to parietal peritoneum (P < 0.05). Immunoreactive TGF-beta1 and TGF-beta3 protein were present in various cell types in these tissues with intensity reflecting their mRNA and protein expression. In conclusion, we provided evidence that serosal tissue of various peritoneal organs and adhesions express TGF-beta1 and TGF-beta3. Since TGF-beta is expressed differently in these tissues and tissue injury often alters the expression of TGF-beta, we propose that tissues with a higher basal expression of TGF-beta may become predisposed to develop more adhesions compared to others.

Intracavitary radiotherapy for refractory dysfunctional uterine bleeding. A case report.

BACKGROUND: Pelvic irradiation was once a common treatment for dysfunctional uterine bleeding (DUB). Today the majority of women with DUB are successfully treated with hormonal therapy; patients unresponsive to hormonal therapy may require endometrial ablation or hysterectomy. We present a patient with severe, intractable DUB and contraindications to surgery who was treated with intracavitary radiotherapy. CASE: A 39-year-old, 150-cm-tall, 310-kg woman was referred for management of severe DUB refractory to medical management. The bleeding was successfully treated with intracavitary cesium. Hysterectomy was not recommended due to the operative risks posed by the patient's massive obesity. Because of technical difficulties during a previous dilation and curettage and the expense of long-term GnRH agonist therapy, the patient elected to undergo intracavitary radiotherapy. CONCLUSION: In selected patients, intracavitary radiotherapy can be used to treat DUB when conventional therapy fails or is contraindicated.

The expression of transforming growth factor-beta s and TGF-beta receptor mRNA and protein and the effect of TGF-beta s on human myometrial smooth muscle cells in vitro.

In this study we investigated the expression of transforming growth factor-beta (TGF-beta) isoform and TGF-beta receptor mRNA and protein, and the effect of TGF-beta 1-3 on the rate of DNA synthesis and proliferation of human myometrial smooth muscle cells in vitro. To determine these, we utilized primary cultures of myometrial smooth muscle cells, standard and competitive quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, enzyme-linked immunoassay, radioreceptor assay, [3H] thymidine incorporation and cell proliferation assay. Standard RT-PCR and immunocytochemistry revealed that myometrial smooth muscle cells express TGF beta 1-3 and TGF-beta type I-III receptor (TGF-beta R) mRNA and protein. Quantitative RT-PCR, using an external synthetic RNA standard, indicated that the cells express 10 copies/cell of TGF-beta 1 and TGF-beta 2, less than one copy/cell of TGF-beta 3 and TGF-beta type IR, three copies/cell of type IIIR, and > 200 copies/cell, of TGF-beta type IIR mRNA. The cells also synthesized and released TGF-beta 1 at the rate of 7.8 +/- 0.7 ng/10(6) cells, of which 1.4 +/- 0.2 ng/10(6) cells was in an active form. The rate of [3H] thymidine incorporation or proliferation of subconfluent quiescent smooth muscle cells was not altered by TGF-beta s (0.1-10 ng/ml) under serum-free conditions, nor in the presence of 10% fetal bovine serum (FBS). TGF-beta 1-3 at 0.25-0.5 ng/ml in the presence of 2% FBS, which induces half maximal stimulation of these cells, stimulated the rate (P < 0.05), whereas at higher doses it reduced the rate of [3H]-thymidine incorporation compared to the controls. The effect of TGF-beta was partially reversible using neutralizing antibodies specific to TGF-beta 1, TGF-beta 2 (10 micrograms/ml) or TGF-beta 3 (3-6 micrograms/ml). TGF-beta s had no significant effect on cell proliferation determined by cell counting. The data indicate that human myometrial smooth muscle cells express the necessary components of the TGF-beta system, suggesting an autocrine/paracrine role for TGF-beta s in myometrium.

Contrast-enhanced magnetization transfer saturation imaging improves MR detection of herpes simplex encephalitis.

Cranial MR imaging was performed in three patients in whom herpes simplex encephalitis was subsequently proved. In all cases, the postcontrast T1 weighted MR images obtained with magnetization transfer saturation showed greater central nervous system involvement than was apparent on the conventional MR images. Specifically, the postcontrast magnetization transfer images were superior at delineating generalized meningeal enhancement as well as focal areas of brain involvement not seen on noncontrast T2-weighted images orconventionalpostcontrast T1-weightedimages.

Perineural spread of rhinocerebral mucormycosis.

An unusual pathway of local spread of rhinocerebral mucormycosis is presented with MR and pathologic correlation. Perineural extension, proved with pathology, followed the trigeminal nerve to the pons. Enhancement of the nerve was seen on MR.

Increased maternal age and the risk of fetal death.

BACKGROUND: Although the fetal death rate has declined over the past 30 years among women of all ages, it is unknown whether particular characteristics of the mother, such as age, still affect the risk of fetal death. We undertook a study to determine whether older age, having a first child (nulliparity), or other characteristics of the mother are risk factors for fetal death. METHODS: We used data from the McGill Obstetrical Neonatal Database to evaluate risk factors for fetal death among all deliveries at the Royal Victoria Hospital in Montreal (n = 94,346) from 1961 through 1993. Data were available for two time periods (1961 through 1974 and 1978 through 1993); data for 1975 through 1977 have not been entered into the data base and were therefore not included. Using logistic regression, we estimated the effect of specific maternal characteristics and complications of pregnancy on the risk of fetal death. RESULTS: The fetal death rate decreased significantly from 11.5 per 1000 total births (including live births and stillbirths) in the 1960s to 3.2 per 1000 in 1990 through 1993 (P < 0.001). Between these periods, the average maternal age at delivery increased from 27 to 30 years (P < 0.001), and the frequency of the diagnosis of diabetes and hypertension during pregnancy increased fivefold (P < 0.001). Nevertheless, after we controlled for these and other maternal characteristics, women 35 years of age or older continued to have a significantly higher rate of fetal death than their younger counterparts (odds ratio for women 35 to 39 years of age as compared with women < 30 years of age, 1.9; 95 percent confidence interval, 1.3 to 2.7; for those 40 or older, 2.4; 95 percent confidence interval, 1.3 to 4.5). CONCLUSIONS: Changes in maternal health and obstetrical practice have resulted in a 70 percent decline in the rate of fetal death among pregnant women of all ages since the 1960s. Advancing maternal age, however, continues to be a risk factor for fetal death.

Expression of messenger ribonucleic acid and presence of immunoreactive proteins for epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and EGF/TGF alpha receptors and 125I-EGF binding sites in human fallopian tube.

Reverse transcription polymerase chain reaction (RT-PCR) revealed that the Fallopian tubes express epidermal growth factor (EGF), transforming growth factor (TGF alpha), and EGF receptor (EGF-R) mRNA. The RT-PCR product was verified by restriction enzyme digestion analysis. Immunohistochemically, EGF, TGF alpha, and EGF-R were localized in Fallopian tubes by use of specific antibodies to human EGF, mature fragments of human TGF alpha, and monoclonal antibodies to the extracellular binding domain of EGF-R. The tubal epithelial cells were the primary site of immunoreactive EGF, TGF alpha, and EGF-R, which were present to a lesser extent in the stromal cells, smooth muscle cell layers, fibroblasts of serosal tissue, and arterial endothelial and smooth muscle cells. Using antibodies generated against the amino and carboxy termini of TGF alpha precursor produced a similar cellular distribution to that observed for mature TGF alpha. The intensity of immunoreactive TGF alpha with these antibodies was similar to that seen with EGF. The ciliated and nonciliated epithelial cells in the ampullary and isthmus regions immunostained with similar intensity for EGF, TGF alpha, and EGF-R. The immunostaining for EGF, TGF alpha, and EGF-R was cycle-dependent, was considerably higher during late proliferative and early-to-mid-secretory phases than during early proliferative and late secretory phases of the menstrual cycle, and was reduced during the postmenopausal period. Specimens obtained 5-12 yr after tubal ligation immunostained for EGF, TGF alpha, and EGF-R similarly to sections from unligated tubes taken during the same phase of the cycle. Quantitative autoradiography of 125I-EGF binding generated a pattern similar to that of immunostaining for EGF-R binding. Net grain density/100 microns 2 calculated for different cell types indicated that the epithelial cells had a significantly higher grain density than did other tubal cell types (p < 0.05) without the cycle dependency seen in the immunohistochemical study. In summary, the results demonstrate that the human Fallopian tube expresses mRNA and contains immunoreactive proteins for EGF, TGF alpha, and EGF-R as well as binding sites for 125I-EGF. The cycle dependency and lower immunostaining in postmenopausal tubes suggest a potential regulation of their expression by ovarian steroids. The results imply the importance of EGF/TGF alpha in a variety of tubal biochemical and physiological functions and possibly early embryonic development.

Radiographic features useful for establishing patient identity from improperly labeled portable chest radiographs.

Radiologists in hospital practice often encounter radiographs that either bear no patient identification or are incorrectly labeled as those of a different patient. To avoid repeating these improperly labeled radiographs, and to establish correct patient identity, most radiologists compare these radiographs with previous radiographs of several patients. This happens most often with portable chest radiographs. To study the reliability of various surgical, pathologic, and anatomic features and to help establish a fast and accurate method of establishing the correct patient identity, we performed a retrospective study of 50 patients in the intensive care unit. The characteristic location and configuration of surgical material, fractures, and dense parenchymal/pleural scars with or without calcifications are extremely helpful in establishing patient identity. In the vast majority of patients who lack such characteristic surgical and pathologic features, the anatomic structures that are most reliable for identification purposes are, in order of decreasing reliability, the transverse processes of the first thoracic vertebrae and the adjoining tubercles of the first ribs, the spinous processes, and the scapular wings. We believe that this information will help radiologists to identify the right patient when radiographs are incorrectly labeled.

Maternal nutrition and spontaneous preterm birth.

Previous studies suggesting that maternal undernutrition increases the risk of preterm birth have suffered from several methodological shortcomings, including use of total gestational weight gain rather than net rate of gain in maternal tissue, inclusion of induced preterm deliveries, and error-prone gestational age measurements based solely on menstrual dates. The authors have attempted to overcome these shortcomings by investigating the potential etiologic roles of prepregnancy body mass index, net rate of maternal weight gain, height, and a number of other potential biological and sociodemographic determinants of spontaneous (i.e., noninduced) preterm birth in a cohort of 13,102 women with early ultrasound-confirmed gestational age who delivered at the Royal Victoria Hospital in Montreal, Quebec, Canada, between January 1, 1980 and March 31, 1989. Total weight gain, but not body mass index, was highly significantly associated with spontaneous preterm birth, averaging 14.6, 12.5, 9.9, and 9.1 kg, in women delivering at 37 or more, less than 37, less than 34, and less than 32 completed weeks, respectively. Although the relation persisted when weight gain was expressed as an overall rate, it disappeared when the analysis was based on net rate; mean net rates of gain were 0.28, 0.29, 0.27, and 0.27 kg/week, respectively. On the basis of multiple logistic regression analyses, significant determinants of birth at less than 37 weeks included maternal short stature; noncompletion of high school; unmarried status; smoking; diabetes; urinary tract infection within 2 weeks of delivery; prepregnancy hypertension; severe pregnancy-induced hypertension; and previous history of preterm delivery, low birth weight, or neonatal death. Most of these factors retained their significance for birth at less than 34 and less than 32 weeks. In fact, the effect of low maternal education was even stronger at these more severe "levels" of preterm birth. The authors conclude that prepregnancy weight-for-height and gestational weight gain are not important determinants of spontaneous preterm birth and that some previous studies have mistaken an effect of shortened gestation for its cause. Other biologic and social determinants, however, indicate priorities for future research and intervention.

Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates.

Despite widespread acceptance of the concept of very low birth weight (VLBW), i.e., birth weight of less than or equal to 1,500 g, VLBW infants represent an extremely heterogeneous group of newborns, including those with very immature gestational age and those who are more mature but extremely growth retarded. To demonstrate how use of the VLBW rubric can lead to confounding bias that is not only large in magnitude but impossible to control satisfactorily, the authors divided 640 consecutive live neonates born in the Royal Victoria Hospital, Montreal, Canada, from 1978 to 1987 into two overlapping groups: a VLBW cohort (birth weight, 500-1500 g; n = 573) and a gestational age cohort (gestational age, 23-30 completed weeks; n = 466). Variation in growth status by gestational age was much more uniform in the 23- to 30-week cohort. Thus, although mean birth weight was similar in the 500- to 1,500-g and 23- to 30-week cohorts (1,055 vs. 1,064 g), the 500- to 1,500-g cohort was more mature (mean gestational age, 28.8 vs. 27.8 weeks; upper range, 39.7 vs. 30.9 weeks) and had twice the rate of intrauterine growth retardation (25.7 vs. 11.5%). These differences in maturity and growth resulted in a misleading protective effect of intrauterine growth retardation against in-hospital death in the 500- to 1,500-g cohort (crude odds ratio = 0.55 (95% confidence interval 0.36-0.83] and a greater discrepancy in maturity between cesarean- and vaginally delivered infants (3.1 vs. 1.5 weeks) in the 500- to 1,500-g vs. 23- to 30-week cohorts. These differences arise from inextricable confounding of growth status and maturity in the 500- to 1,500-g cohort, the most mature infants also being the most growth retarded. The removal of well-grown infants with birth weights of greater than 1,500 g from the VLBW cohort leads to a progressively distorted spectrum of growth with advancing gestational age and an artifactual blunting of the beneficial effects of increasing maturity. The authors suggest that whenever fetal growth is an important exposure, outcome, or confounding variable, epidemiologic studies of extremely small or immature newborns should be based on gestational age rather than the VLBW criterion.

Postterm infants: too big or too small?

Concern over the postterm pregnancy has shifted from that of the difficult delivery of an excessively large fetus to the current concern with death in utero of an undernourished, small-for-date fetus. Studies of postterm pregnancy before the availability of ultrasonography may have included a large proportion of erroneous menstrual dates. The present study of 7000 infants was undertaken to reassess fetal growth in postterm pregnancies in which the expected date of confinement from last normal menstrual period dating was confirmed (+/- 7 days) by early ultrasonography. Results show a gradual shift toward higher birth weight and greater crown-heel length and head circumference between 273 and 300 days of gestational age. No evidence of postterm weight loss or lower weight for length could be demonstrated. Concern in postterm pregnancy should be for fetal macrosomia, not for intrauterine growth retardation.

Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome.

Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of fetal growth and body proportionality.

Previous studies of fetal growth and body proportionality have been based on error-prone gestational age estimates and on inappropriate comparisons of infants with dissimilar birth weights. Based on a cohort of 8719 infants with validated (by early ultrasonography) gestational ages and indexes of body proportionality standardized for birth weight, potential maternal and fetal determinants of fetal growth and proportionality were assessed. Maternal history of previous low birth weight infants, pregnancy-related hypertension (particularly if severe), diabetes, prepregnancy weight, net gestational weight gain, cigarette smoking, height, parity, and fetal sex were all significantly associated with fetal growth in the expected directions. Consistent with previous reports, maternal age, marital status, and onset or total amount of prenatal care had no significant independent effects. Fetal growth ratio (relative weight for gestational age), pregnancy-related hypertension, fetal sex, and maternal height were the only significant determinants of proportionality. Infants who were growth-retarded, those with taller mothers, those whose mothers had severe pregnancy-related hypertension, and males tended to be longer and thinner and had larger heads for their weight, although these variables explained only a small fraction of the variance in the proportionality measures. Among infants with intrauterine growth retardation, gestational age was not independently associated with proportionality (in particular, late term and post-term infants did not tend to be more disproportional), a finding that does not support the hypothesis that earlier onset of growth retardation leads to more proportional growth retardation. The results raise serious questions about previous studies of proportionality, particularly those suggesting a nutritional etiology for proportional intrauterine growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)