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PubMed1997

Reproductive performance of lactating dairy cows following estrus synchronization regimens with PGF2alpha and progesterone.

The objective of this study was to evaluate the reproductive performance of lactating cows in seasonal dairy herds after estrus synchronization with PGF2alpha (PG) with or without supplementation with progesterone (P4). In Trial 1, synchronized cows (S1; n = 521) were compared with untreated control cows (C; n = 518) in 5 herds. Estrus of cows in the S1 group was synchronized with 2 treatments of PG (Lutalyse) 13 d apart. The breeding season started 2 d after the second PG. Cows were first bred by AI for 7 wk and then herd sires were used. Compared with C cows, estrus synchronization in the treated cows reduced the conception rate to first AI (61.1 vs 70.5%; P < 0.01) and the intervals from start of the breeding season to conception for cows conceiving to AI (11.0 vs 14.6 d; P < 0.05) or to both AI and natural mating (16.5 vs 18.4 d; P < 0.05). There was no effect on conception rate to second AI (68.8%), on pregnancy rate by Day 24 (72.3%) or Day 49 (86.3%) of the breeding season, or on the percentage of cows not pregnant at end of the breeding season (5.0%). In Trial 2, effects of P4 supplementation before the second PG on reproductive performance were evaluated in 4 herds. Estrus of each cyclic cow was synchronized with PG as in Trial 1. Half of the cows in each herd were treated with an intravaginal P4 device (CIDR) for 5 d before the second PG (S2+P4, n = 608), whereas the remaining half received no CIDR treatment (S2, n = 593). Compared with S2 cows, P4 treatment increased the estrous response rate to the second PG (89.6 vs 82.9%; P < 0.01), the conception rate to first AI (65.1 vs 59.7%; P = 0.07), the pregnancy rate by Day 6 of the breeding season (59.3 vs 49.0%; P < 0.001), and reduced the intervals from start of the breeding season to conception for cows conceiving to AI (8.6 vs 10.4 d; P < 0.10) or to both AI and natural mating (12.7 vs 16.4 d; P < 0.01). Treatment with a used CIDR from Days 16 to 21 after start of breeding to re-synchronize returns to service had no effect on conception rate to first or second AI but may decrease the conception rate to second AI in cows previously treated with CIDR. In conclusion, estrus synchronization with the double PG system can reduce fertility, while P4 supplementation for 5 d before the second PG can improve estrous response and overall reproductive performance. Stage of the estrous cycle at the time of the second PG can affect fertility following synchronization.

Journal Article↗

PubMed2003

Quorum sensing and expression of virulence in Escherichia coli O157:H7.

Enterohaemorrhagic Escherichia coli O157:H7 causes a characteristic histopathology in intestinal cells known as attaching and effacing lesion. The genes for the lesion are encoded by the Locus of Enterocyte Effacement (LEE) pathogenicity island, that encodes a type III secretion system, the intimin intestinal colonization factor, and the translocated intimin receptor protein that is translocated from the bacterium to the host epithelial cells. Expression of the operons encoded within LEE is complex, but recent studies have demonstrated that quorum sensing influences transcription from four of the LEE operon promoters. A transcriptional regulator (LuxR homologue), signal synthase (LuxI homologue), and autoinducer (acylhomoserine lactone) are indispensable for this system in most gram-negative bacteria. Vibrio harveyi, a gram-negative bioluminescent marine bacterium, regulates light production in response to two autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone produced by most gram-negative bacteria. The structure of AI-2 is not known, but many species of gram positive and gram-negative bacteria, including E. coli and more specifically O157:H7, have been shown to produce AI-2 depending on the function encoded by the luxS gene. The LuxS acts as an AI-2 synthase and the AI-2 is produced from S-adenosylmethionine in three enzymatic steps. The substrate for LuxS is S-ribosylhomocysteine, which is cleaved to form two products, one of which is homocysteine, and the other is AI-2. The biosynthetic pathways and the biochemical intermediates in AI-2 biosynthesis have been observed to be identical in several gram-negative bacteria, such as E. coli, Salmonella typhimurium, V. harveyi, Vibrio cholerae, and Enterococcus faecalis. Thus, unlike quorum sensing via the family of related homoserine autoinducers, AI-2 is a universal signal, which may be used by a variety of bacteria for communication among and between species and may be responsible for regulation of virulence genes in E. coli O157:H7.

Escherichia coli O157↗

PubMed2002

Macromolecule absorption and cortisol secretion in newborn calves derived from in vitro produced embryos.

Earlier reports indicate that calves derived from in vitro produced (IVP) embryos are more susceptible to neonatal disease than calves produced after artificial insemination (AI) or natural mating. The aims of the present study were to investigate whether calves born after IVP embryos show an altered macromolecule absorption (immunoglobulin G (IgG) and porcine serum albumin (PSA)) compared with AI calves and whether the macromolecule absorption could be related to the degree of acidosis or to the cortisol secretion around birth. Hence, IgG and PSA absorption in control AI calves (n=7) was compared with that in two groups of IVP calves (IVP-defined: SOFaa embryo culture with polyvinyl alcohol, n=6; IVP-serum: SOFaa embryo culture with serum and co-culture, n=8). The calves were fed colostrum (40ml/kg) at 2, 6 and 12h after birth. At 24h after birth, both AI and IVP calves had achieved a level of plasma IgG sufficient to provide passive immunization (>15mg/ml). When the values were adjusted for the varying colostral IgG contents and the degree of acidosis, the IVP-defined calves had significantly lower peak plasma IgG concentrations than the AI calves at 18-24h after birth (P<0.04). However, when the macromolecule marker (PSA), was fed to all calves at 2 and 12h after birth the resulting plasma PSA levels were significantly lower in the AI calves compared with the IVP calves during the whole observation period (P<0.0001). Calves with a moderate neonatal acidosis (mean pH<7.2 during the first 30min after birth) had reduced peak plasma IgG concentration at 18-24h after birth (P<0.02) compared to calves without acidosis. The basal and ACTH-stimulated cortisol levels were lower in the newborn IVP-defined calves than in the AI calves (P<0.05) and the IVP-serum calves (P<0.002). Cortisol levels shortly after birth correlated positively with birth weight (r=0.60, P<0.0001) and with gestation length (r=0.34, P<0.04). Since, the IVP calves absorbed sufficient amounts of IgG from colostrum to acquire sufficient passive immunity, we conclude that the lower viability described in IVP offspring probably is not caused by an impaired passive immunization. IVP-defined calves had significantly lower absorption efficiency of IgG compared with AI calves, whereas absorption of a non-Ig macromolecule (PSA) was higher for IVP than AI calves. This might indicate a more selective absorption in AI calves in favor of IgG. Acidosis around birth affected immunoglobulin absorption negatively. IVP-defined calves had significantly lower cortisol levels the first 3h after birth and during an ACTH-challenge and a lower IgG absorption efficiency, which might indicate a mild degree of organ dysmaturity in these calves.

Absorption↗

PubMed2001

Correction of carotid augmentation index for heart rate in elderly essential hypertensives. ANBP2 Investigators. Australian Comparative Outcome Trial of Angiotensin-Converting Enzyme Inhibitor- and Diuretic-Based Treatment of Hypertension in the Elderly.

Carotid augmentation index (AI) is used as a surrogate measure of arterial stiffness. Although arterial stiffness has been shown to either remain unchanged or increase with an increase in heart rate, AI decreases as heart rate increases. This study aimed to quantify this confounding effect of heart rate on AI. We investigated 873 hypertensives, mean age 72 +/- 5 years, 44% men, mean brachial blood pressure 161 +/- 21/82 +/- 11 mm Hg. Carotid artery tonometry with simultaneous continuous wave Doppler measurement of ascending aortic blood flow was performed. AI was calculated from the carotid pressure waveform. Waveforms were decomposed into their forward and backward components and the time to reflection between the maxima of the forward and backward pressure waves was measured. AI showed a stronger (P < .001) association with ejection time (r = 0.48, P < .001) than with heart rate (r = -0.28, P < .001). Although AI is strongly related to the time to reflection (r = -0.51, P < .001), only a weak association was seen between time to reflection and heart rate (r = 0.16, P < .001) or ejection time (r = -0.12, P < .001). Our analysis in an elderly cohort of patients with essential hypertension demonstrates that AI is related to the time to reflection. It also reiterates that AI is confounded by heart rate without any underlying heart rate-dependent change in wave reflection. In population-based studies the confounding effect of heart rate can potentially be corrected. AI remains strongly (r = -0.52) related to time to reflection after correction for the effects of ejection time on AI.

Aged↗

PubMed1998

Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus infection in pregnant women.

BACKGROUND: Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from non-primary infection in pregnant females. IgM tests often used for this purpose are not reliable enough. OBJECTIVE: To evaluate an HCMV-IgG urea-elution assay for its ability to distinguish primary from non-primary infection. In this assay, soaking the antigen-antibody complex with an urea containing solution frees antibodies with low avidity but has no influence on those with high avidity. An avidity index (AI) was calculated: AI = (OD with urea/OD without urea) x 100. STUDY DESIGN: HCMV-IgG avidity was measured on a single serum of 79 patients with past infection (pregnant women, graft recipients and blood donors) and of 63 patients (78 sera) with documented seroconversion (pregnant women and graft recipients). Sixty-one pregnant women positive or equivocal for HCMV-IgM but without a documented seroconversion were included in this study. RESULTS: Most (72/79) of the patients with past infection had an AI > 65% and all but one had an AI > 50%. In pregnant women, in the case of a primary infection within the past 3 months, AI are usually (51/53) < 50% and never > 65%. Among the IgM positive pregnant women who lack a seroconversion history, 38 had AI > 65% suggestive of an infection that had occurred at least 3 months earlier, 11 had an AI in a grey area between 50 and 65% and 12 had an AI < 50%, suggestive of a recent primary infection. CONCLUSIONS: In pregnant women, measurement of the IgG avidity may help to date a HCMV infection, an AI > 65% highly suggests a past infection while an AI < 50% corresponds to a recent primary infection.

Antibody Affinity↗

PubMed2001

Adjuvant trials of aromatase inhibitors: determining the future landscape of adjuvant endocrine therapy.

This review will discuss the role of aromatase inhibitors (AIs) in the adjuvant setting, and will summarize major strategies behind individual adjuvant trials using aromatase inhibitors. Studies with the third generation AIs including anastrozole, letrozole and exemestane, have shown better outcome and improved therapeutic ratio over second line hormonal approaches (i.e. progestins or aminoglutethimide) and, more recently, over tamoxifen also. These promising results have led recently to testing of AIs in the adjuvant setting for postmenopausal patients. Most trials now in progress are evaluating the role of new AIs versus tamoxifen (T) given x 5 years, which in most institutions is currently the standard hormonal adjuvant therapy for breast cancer. Three adjuvant approaches are being tested. First is the use of AI+T x 5 years in combination versus each agent alone, as reflected in the recently completed ATAC trial. Second is a sequential approach T first x 2-3 years followed by AIs x 2-3 years, or the other way round; and third, T x 5 years followed by AIs for additional 5 years (i.e. total duration of adjuvant hormones of 10 years). Many patients in the above trials will survive their first cancer. Hence, the non-oncological outcomes known to be affected by hormones are of rising importance. Therefore, the assessment of lipids as surrogates for cardiovascular morbidity, and of bone mineral status, as a marker for osteoporosis/bone fractures, is an important component of these trials. Also discussed in this review are proposals for future studies of AIs with focus on hormone resistance, such as early alteration of multiple hormonal agents or their intermittent use, the impact of the new generation of SERMs or 'pure' antiestrogens on activity of AIs, and the rising importance of AIs interacting with biologicals, cytokines or hormone modulators.

Aromatase Inhibitors↗

PubMed2006

Structural analysis and assembly of the HIV-1 Gp41 amino-terminal fusion peptide and the pretransmembrane amphipathic-at-interface sequence.

The amino-terminal region within the HIV-1 gp41 aromatic-rich pretransmembrane domain is an amphipathic-at-interface sequence (AIS). AIS is highly conserved between different viral strains and isolates and recognized by the broadly neutralizing 2F5 antibody. The atomic structure of the native Fab2F5-bound AIS appears to involve a nonhelical extended region and a beta-turn structure. We previously described how an immunogenic complex forms, based on the stereospecific interactions between AIS and the gp41 amino-terminal fusion peptide (FP). Here, we have analyzed the structure generated by these interactions using synthetic hybrids containing AIS and FP sequences connected through flexible tethers. The monoclonal 2F5 antibody recognized FP-AIS hybrid sequences with an apparently higher affinity than the linear AIS. Indeed, these hybrids exhibited a weaker capacity to destabilize membranes than FP alone. A combined structural analysis, including circular dichroism, infrared spectroscopy, and two-dimensional infrared correlation spectroscopy, revealed the existence of specific conformations in FP-AIS hybrids, predominantly involving beta-turns. Thermal denaturation studies indicated that FP stabilizes the nonhelical folded AIS structure. We propose that the assembly of the FP-AIS complex may act as a kinetic trap in halting the capacity of FP to promote fusion.

Amino Acid Sequence↗

PubMed2005

Neurophysiological assessment of lower-limb voluntary control in incomplete spinal cord injury.

STUDY DESIGN: Cross-sectional retrospective study of a neurophysiological method of voluntary motor control characterization. OBJECTIVES: This study was undertaken to validate the surface electromyography (sEMG)-based voluntary response index (VRI) as an objective, quantitative, laboratory measure of spinal cord injury severity in terms of voluntary motor control disruption. SETTING: VA Medical Centers in Houston and Dallas Texas, USA. METHODS: A total of 67 subjects with incomplete spinal cord injury (iSCI), American Spinal Injury Association Impairment Scale (AIS)-C (n = 32) and -D (n = 35) were studied. sEMG recorded during a standardized protocol including eight lower-limb voluntary motor tasks was analyzed using the VRI method that relates multi-muscle activation patterns of SCI persons to those of healthy-subject prototypes (n = 15). The VRI is composed of a measure of the amount of the sEMG activity (magnitude) and the distribution of activity across muscle groups compared to that of healthy subjects for each motor task (similarity index, SI). These resulting VRI components, normalized magnitude and SI, were compared to AIS clinical findings in this study. Receiver operating characteristic analysis was performed to determine the SI values best separating AIS-C and AIS-D subjects. RESULTS: Magnitude and SI for AIS-C subjects had mean values of 0.27 +/- 0.32 and 0.65 +/- 0.21, respectively. Both parameters were significantly larger in the AIS-D subjects (0.78 +/- 0.43 and 0.93 +/- 0.06), respectively (P < 0.01). An SI value of 0.85 was found to separate AIS-C and AIS-D groups with a sensitivity of 0.89 and a specificity of 0.81. Further, the VRI of each leg strongly correlated with the respective AIS motor score (0.80, r < 0.01). CONCLUSIONS: In the domains of voluntary motor control, the sEMG-based VRI demonstrated adequate face validity and sensitivity to injury severity as currently measured by the AIS. SPONSORSHIP: Veterans Affairs Medical Center.

Adult↗

PubMedDate not supplied

Insemination factors affecting the conception rate in seasonal calving Holstein-Friesian cows.

Differences in conception rate to first service between artificial inseminations (AI) carried out by commercial AI operators (CAI) or do-it-yourself operators (DIY), between natural service (NAT) and AI, between different AI sires, and between fresh and frozen-thawed semen, on Irish commercial dairy farms, were studied using logistic regression. The study comprised 12,933 potential first inseminations from 77 spring-calving dairy herds. The data were recorded during 1999 and 2000. Amongst the total, 4,394 cows had repeated records across the two years. Adjustment variables included: herd, year, parity, calving period, calving to service interval, herd size, proportion of North American Holstein-Friesian genes, peak milk yield, semen fresh or frozen-thawed status, AI sire and a cow history variable to account for the correlation structure that may exist between performance records of cows present in both years of the study. Interactions of interest were tested but were non-significant. No significant association was observed between the category of AI operator and the likelihood of conception rate to first service (PREG1). The variation in PREG1 observed within the category of operator (CAI and DIY) was investigated using the Levene test for homogeneity of variance. There was no difference between the level of variation observed within CAI and DIY operators. There were significant differences in the likelihood of PREG1 between different AI sires. Amongst the 40 most commonly used AI sires, 3 sires had a lower likelihood of PREG1 (P < 0.05) when compared to the reference AI sire (sire with PREG1 similar to the mean of the group). There was a tendency for a reduced likelihood of PREG1 with the use of fresh semen compared to frozen-thawed semen (OR = 0.80, P = 0.067). Amongst the adjustment variables in the model, those significantly associated with the likelihood of PREG1 included the herd, calving period, calving to first service interval and peak milk yield. No significant difference in the likelihood of PREG1 was observed between AI and NAT.

Animal Husbandry↗

PubMed2002

Ultrasonographic risk score of carotid plaques.

OBJECTIVE: to determine the relative significance of ultrasonographic parameters of carotid plaques to develop an Activity Index (AI) which could correlate with clinical findings. METHOD: two hundred and fifteen plaques in 141 patients underwent ultrasonography and computer-assisted structural analysis. In half the patients (group 1), plaques were classified as either homogeneous and heterogeneous and ultrasonographic appearances related symptomatic (SP) or asymptomatic (AP) station. The probability of SP for each ultrasound parameter was used to define an Activity Index (AI). The AI was then applied the second half of patients (Group 2) to assess the value of AI in determining symptomatic station. RESULTS: the parameters with highest morbility were surface disruption, severe stenosis and low grey scale median and, additionally in heterogenous plaques heterogeneity and the presence of a juxta-luminal echolucent area. The power in group 2 of AI to identify symptomatic plaques was determined. Mean AI was for SP-75 (41-100) and for AP-43 (22-100); 78% of SP have AI>60 and 70% of AP have AI<50. The cut-off point between the two groups was 52. ROC curve analysis of the AI were obtained to determine its diagnostic accuracy. CONCLUSION: Activity Index is an objective parameter of plaque echostructure that positively correlates with symptoms. AI may contribute to better selection for treatment of patients with carotid artery disease.

Adult↗

PubMed1997

A high apoptotic index occurs in subtypes of endometrial adenocarcinoma associated with a poor prognosis.

A study was carried out to determine the apoptotic index (AI) in cases of endometrial adenocarcinoma that are usually associated with a poor prognosis, and to identify in the AI in these cases differs from the AI's in grade I and II endometrial adenocarcinoma. The apoptotic index (defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in counting 3000 tumor cells) was calculated for five grade III endometrial adenocarcinomas of no specific type (NST), five clear cell adenocarcinomas (CCC), three high grade uterine papillary serous carcinomas (UPSC) and one undifferentiated carcinoma of the endometrium. Overall a higher mean AI (6.3%) was identified in these poor prognosis neoplasms than in 13 grade I and II endometrial adenocarcinomas (mean AI 2.7% p < 0.0001). The apoptotic index was highest in the undifferentiated carcinoma (AI = 9.7%). The mean AI for the cases of UPSC, CCC and grade III endometrioid (NST) adenocarcinomas were 7.4%, 5.9% and 5.2% respectively. There was no evidence of a statistically significant difference in the AI in these poor prognosis groups (Kruskall Wallis test p = 0.45). Although the results show that a high AI is a feature of poor prognosis endometrial carcinoma, no distinction in AI was demonstrated in the subtypes examined.

Adenocarcinoma↗

PubMed2006

Analysis of the acidity index and integrated intragastric acidity in 645 patients presenting with gastroesophageal reflux disease symptoms.

OBJECTIVE: In a recent study of patients receiving proton-pump inhibitor (PPI) therapy, a new parameter, the acidity index, was described as being less complicated to calculate and of comparable accuracy (r = 0.93) to integrated intragastric acidity (IA) in assessing intragastric pH control. The aim of this study was to correlate AI with IA using a large database of ambulatory 24-h pH-metry studies in untreated patients presenting with gastroesophageal reflux disease (GERD) symptoms. MATERIAL AND METHODS: We retrospectively analyzed 645 studies obtained from 1995 to 2001. Daytime (0800 h-2200 h), night-time (2200 h-0800 h) and 24-h IA and AI were calculated according to age, gender and the presence or absence of GERD, and correlations between these parameters were assessed using linear regression with F-statistic values, p-values and Akaike's Information Criterion values. GERD was defined as total esophageal pH time <4.0, 5 cm above the lower esophageal sphincter, for > or =4.2% of the day. IA and AI were calculated as follows: IA (mmol x h/l) = summation operator(acid in mmol/l at time "t" + acid in mmol/l at time "t - 1")/2 x ("t"-"t - 1"); AI = (%time pH < 4-%time pH < 3) x 1+(%time pH < 3-%time pH < 2) x 10+(%time pH < 2-%time pH < 1) x 100 + (%time pH < 1-%time pH < 0.8) x 1000. RESULTS: Overall, the mean 24-h IA value was 882.0+/-820.0 mmol x h/l (daytime 392.0+/-400.0, night-time 490.0+/-486.0). The mean 24-h AI value was 102.0+/-87.0 (daytime 86.0+/-80.0, night-time 120.0+/-114.0, p < 0.001). The mean 24-h IA value was 1057.0+/-829.4 mmol x h/l (daytime 459.8+/-406.0, night-time 597.2+/-500.4, p < 0.001) in GERD patients and 713.0+/-775.0 mmol x h/l (daytime 326.0+/-383.0, night-time 387.0+/-448.5) in non-GERD patients (p < 0.001). The mean 24-h AI value was 122.1+/-88.1 (daytime 101.4+/-82.5, night-time 145.3+/-120.7) in GERD patients and 83.0+/-81.0 (daytime 71.0+/-73.9, night-time 96.4+/-102.6) in non-GERD patients (p < 0.001). Our statistical modeling demonstrated that the correlation between the acidity index and IA becomes progressively poorer with increasing values of acidity. CONCLUSIONS: We conclude that gastric acid production assessed by both IA and AI is higher during evening hours in comparison with daytime hours and the difference between night-time and daytime values is statistically significant. In addition, gastric acid production assessed by both IA and AI is significantly higher in GERD patients than non-GERD patients. This difference is primarily due to differences in nocturnal acid production. The AI correlates poorly with measured IA, especially at higher levels of gastric acidity. Therefore, AI is not an acceptable surrogate for IA in assessing gastric acid production.

Adolescent↗

PubMed2002

The control of H5 or H7 mildly pathogenic avian influenza: a role for inactivated vaccine.

Biosecurity is the first line of defence in the prevention and control of mildly pathogenic avian influenza (MPAI). Its use has been highly successful in keeping avian influenza (AI) out of commercial poultry worldwide. However, sometimes AI becomes introduced into poultry populations and, when that occurs, biosecurity again is the primary means of controlling the disease. There is agreement that routine serological monitoring, disease reporting, isolation or quarantine of affected flocks, application of strict measures to prevent the contamination of and movement of people and equipment, and changing flock schedules are necessities for controlling AI. There is disagreement as to the disposition of MPAI-infected flocks: some advocate their destruction and others advocate controlled marketing. Sometimes biosecurity is not enough to stop the spread of MPAI. In general, influenza virus requires a dense population of susceptible hosts to maintain itself. When there is a large population of susceptible poultry in an area, use of an inactivated AI vaccine can contribute to AI control by reducing the susceptibility of the population. Does use of inactivated vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists MPAI control (which may reduce the risk of highly pathogenic AI (HPAI)) but, unless steps are taken to prevent it, vaccination may interfere with sero-epidemiology in the case of an HPAI outbreak. Does lack of vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists in identification of sero-positive (convalescent) flocks in a HPAI eradication program, but it interferes with MPAI control (which in turn may increase the risk of emergence of HPAI).A number of hypothetical concerns have been raised about the use of inactivated AI vaccines. Infection of vaccinated flocks, serology complications and spreading of virus by vaccine crews are some of the hypothetical concerns. The discussion of these concerns should take place in a scientific framework and should recognize that control of MPAI reduces the risk of HPAI. That inactivated vaccines have reduced a flock's susceptibility to AI infection, have reduced the quantity of virus shed post-challenge, have reduced transmission and have markedly reduced disease losses, are scientific facts. The current regulations preventing vaccination against H5 or H7 MPAI have had the effect of promoting circulation of MPAI virus in commercial poultry and live poultry markets. In the absence of highly pathogenic avian influenza, there is no justification for forbidding the use of inactivated vaccine.

Animals↗

PubMed2006

Autoimplants in serous borderline tumors of the ovary: a clinicopathologic study of 30 cases of a process to be distinguished from serous adenocarcinoma.

The clinical and pathologic features of serous borderline tumors (SBTs) with autoimplants (AIs) were studied with emphasis on their relation to survival, ovarian SBT with a micropapillary pattern, and their distinction from serous adenocarcinoma. The 30 patients ranged in age from 17 to 70 years (mean, 35.8 years). Two had stage I disease, 10 had stage II disease, and 18 had stage III disease. Twenty-five patients had bilateral ovarian tumors. In 28 cases, AIs were present on the surface of the neoplasm or between exophytic surface tumor papillae; in 2 cases, AIs were between papillae within intracystic tumor. The AIs consisted of single cells or glands and clusters of cells with mild to moderate nuclear atypia within a fibroblastic stroma; the stroma dominated over the epithelium in extent within the AI. In many cases, the epithelial cells in the AI had abundant eosinophilic cytoplasm. All but 2 of the patients had coexisting noninvasive peritoneal implants; 3 of them also had invasive peritoneal implants. Six of the SBTs had a micropapillary pattern; 3 of these were stage III and 3 stage II tumors. Clinical follow-up was available for 11 patients. Eight were alive and well after 4 to 7 years (mean, 5 years); 3 of these patients had stage II disease and 5 had stage III disease. Three were dead of disease after 7 to 12 years (mean, 9 years). Two patients who died of disease had stage III disease, and 1 of them had invasive implants. The third patient had stage II disease, invasive implants, and the tumor was of the micropapillary type. Our study indicates that the majority of patients with SBT with AI have stage II or III disease and abundant exophytic tumor. SBTs with AI had a micropapillary pattern in 20% of the cases. AIs do not appear to have an adverse impact on survival when controlled for peritoneal implant type and for this reason must be distinguished from true stromal invasion in serous carcinoma, a misdiagnosis sometimes made, or seriously entertained, initially in these cases. Features that favor AI over carcinoma arising in an SBT are 1) a location between tumor papillae or on the ovarian surface 2) a predominance of stroma over epithelial cells, and 3) the "borderline" cytologic appearance of epithelial cells.

Adolescent↗

PubMed2002

Mitotic activity and apoptosis in endocervical glandular lesions.

To evaluate the significance of mitotic activity and apoptosis in the differential diagnosis of endocervical glandular lesions, we examined the frequency of mitoses and apoptosis in 89 endocervical glandular lesions from 78 patients, which consisted of benign reactive changes (7 cases), lobular or diffuse laminar endocervical glandular hyperplasia (4), microglandular hyperplasia (3), tunnel clusters (7), nabothian cysts (2), mesonephric remnants (3), tubal metaplasia (3), endocervical glandular dysplasias (including atypical tubal metaplasia) (EGD) (7), adenocarcinoma in situ (AIS) (31), microinvasive adenocarcinoma (7), frankly invasive adenocarcinoma (12), and minimal deviation adenocarcinoma (3). Mitotic index (MI; mitotic figures per 1000 cells) was significantly higher in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma than any other lesions examined. Microinvasive adenocarcinoma showed the highest MI. Apoptosis was detected consistently and frequently in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma. AIS showed the highest apoptotic index (AI; apoptoses per 1000 cells). Frequent apoptotic bodies and mitotic figures are a common feature of endocervical glandular malignancies (except for minimal deviation adenocarcinoma) and are an important feature that can facilitate their differentiation from benign and borderline lesions. High MI in microinvasive adenocarcinoma might aid the distinction of microinvasive adenocarcinoma from AIS. Although both MI and AI of EGD were between those of benign reactive changes and of AIS, MI and AI alone are not sufficient to differentiate EGD from benign reactive changes. MI and AI are not helpful in the differential diagnosis between minimal deviation adenocarcinoma and its benign mimics.

Adenocarcinoma↗

PubMed2004

Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

OBJECTIVE: Increased arterial stiffness is a determinant of cardiovascular mortality. Pulse wave velocity (PWV) is a direct measure of arterial stiffness. Aortic augmentation index (AI) and pulse pressure (PP) are surrogate measures of arterial stiffness. Both PWV, AI and PP increase with cardiovascular risk factors. The aim of this study was to test the validity of AI and PP as surrogate measures of arterial stiffness compared with PWV, during beta-adrenergic stimulation with Isoprenaline (Iso). DESIGN AND METHODS: A total of 41 healthy volunteers entered a randomized, double-blind, placebo-controlled, cross-over study. In random order, subjects were given intravenous infusion in equal volume of Iso 8 microg/kg per min (dissolved in glucose 5%) and placebo (glucose 5%). A wash-out period of 25 min was observed between the infusions. Measurements included blood pressure (BP), heart rate (HR), PWV, and AI. PWV were determined using complior (Complior, Artech-Medical, Paris, France). AI and aortic PP were obtained from pulse wave analysis of radial applanation tonometry, using transfer function (SphygmoCor Windows software). RESULTS: Baseline AI increased (P < 0.05) with aging, a lower height and a larger diastolic BP (DBP). Iso increased (P < 0.0001) HR, brachial SBP, brachial and aortic PP as compared with placebo. In contrast, Iso decreased (P < 0.05) AI, brachial DBP, peripheral PWV, but not aortic PWV. Decrease of AI induced by Iso was not related to PWV. In stepwise multiple regression changes in HR, brachial SBP and DBP were independent determinants of AI response to Iso (r = 0.78, P < 0.0001). CONCLUSIONS: Our findings show that AI and PP fail as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Adrenergic beta-Agonists↗

PubMed1996

The Injury Severity Score is unable to differentiate between poor care and severe injury.

UNLABELLED: The Injury Severity Score (ISS) has been the most frequently used tool for stratifying injured patients. The primary hypothesis of this study was that ISS fails to differentiate between severe injury and mismanagement. METHODS: Data models were generated for mismanaged and ideally managed patients for isolated injuries for each body system. Flow charts of care, outcomes, and Abbreviated Injury Scale (AIS) and ISS scores were generated for each model. RESULTS: Multiple models demonstrated that minor injuries that were mismanaged would result in AIS and ISS scores that were the same as ideally managed severe injuries. Three examples are summarized as follows: A comparison of two patients with splenic injuries demonstrates that ISS is unable to differentiate between mismanagement of a minor splenic laceration as compared to a severely lacerated spleen. In the case of the minor injury to the spleen (initial AIS = 2) that was missed by the treating physicians and allowed to bleed into shock and near arrest because of massive hemorrhage that could have been prevented by early recognition and treatment, the final AIS is coded as 4 in this mismanaged patient, the same AIS and ISS as a severely lacerated spleen (AIS = 4) managed well. Both result in a discharge ISS of 16. Similarly, the ISS at discharge is the same for a well-managed severe head injury (AIS = 4) and a mismanaged minor head injury that is unrecognized, progresses and leads to coma (AIS = 4). Finally AIS, ISS does not differentiate between a well-managed cervical fracture with complete cord injury and a mismanaged cervical spine fracture that initially does not involve a cord injury, but because of mismanagement and lack of immobilization, progresses to complete cord injury because of poor care. Both result in the same injury severity assessment (AIS = 5, ISS = 25 in both). CONCLUSIONS: This study demonstrates a fact that should be recognized by all who rely upon the ISS for comparing quality of care: ISS fails to differentiate severe injury from mismanagement of injury. Because the ISS mixes outcome data with injury severity, ISS incorrectly assigns increased severity to the lesser injuries of mismanaged patients. These findings have important implications for use of the ISS in quality of care assessments.

Abbreviated Injury Scale↗

PubMed2003

Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis: a study of 598 patients.

STUDY DESIGN: A cross-sectional study of anthropometric parameters in adolescent idiopathic scoliosis (AIS). OBJECTIVE: To compare anthropometric parameters and growth pattern of AIS girls versus normal controls during peri-puberty. SUMMARY OF BACKGROUND DATA: Abnormal pattern of growth has been reported in AIS patients. The sequential changes of growth and the correlation with curve severity have not been properly studied. MATERIALS AND METHODS: Five hundred ninety-eight AIS girls and 307 healthy girls entered the study. Weight, height, body mass index (BMI), arm span, sitting height, and leg length were determined using standard techniques. Height and sitting height were adjusted by using the greatest Cobb angle to correct for spinal deformity (Bjure's formula). Puberty was graded by Tanner's staging. RESULTS: AIS girls had significantly shorter height (P = 0.001), corrected height (P = 0.005), arm span (P = 0.022), sitting height (P = 0.005) and leg length (P = 0.004) than the controls at pubertal stage I. From pubertal stages II through V, corrected height (P <or= 0.033) and arm span (P <or= 0.038) were significantly longer in the AIS than controls. Corrected sitting height was also longer in AIS from stages II through IV (P <or= 0.043). Furthermore, BMI of AIS was significantly lower than that of controls from stages II through IV (P <or= 0.038). In addition, significant correlations of the curve severity versus weight, BMI, and arm span were also found (P <or= 0.048). CONCLUSIONS: Various body segmental lengths were initially significantly shorter in AIS before puberty. However, after the onset of puberty, significantly longer corrected height, arm span, and various body segments were found. And there were significant correlations between anthropometric parameters and the scoliotic curve severity. Results of this large-scale study revealed the presence of abnormal growth in AIS patients during peripubertal development.

Adolescent↗