Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion.

Phenotypic heterogeneity exists within collectively invading packs of tumor cells, suggesting that cellular subtypes cooperate to drive invasion and metastasis. Here, we take a chemical biology approach to probe cell:cell cooperation within the collective invasion pack. These data reveal metabolic heterogeneity within invasive chains, in which leader cells preferentially utilize mitochondrial respiration and trailing follower cells rely on elevated glucose uptake. We define a pyruvate dehydrogenase (PDH) dependency in leader cells that can be therapeutically exploited with the mitochondria-targeting compound alexidine dihydrochloride. In contrast, follower cells highly express glucose transporter 1 (GLUT1), which sustains an elevated level of glucose uptake required to maintain proliferation. Co-targeting of both leader and follower cells with PDH and GLUT1 inhibitors, respectively, inhibits cell growth and collective invasion. Taken together, our work reveals metabolic heterogeneity within the lung cancer collective invasion pack and provides rationale for co-targeting PDH and GLUT1 to inhibit collective invasion.

Screening for mood disorders after stroke: a systematic review of psychometric properties and clinical utility.

BACKGROUND: Routine mood screening is recommended after stroke. However, clinicians report difficulty selecting appropriate tools from the wide range available. We aimed to systematically review the psychometric properties and clinical utility of mood screening tools for stroke survivors. METHOD: Electronic databases (AMED, EMBASE, CINAHL, Medline and PsycINFO) were searched to identify studies assessing the sensitivity and specificity of mood screening tools. Tools that demonstrated at least 80% sensitivity and 60% specificity with stroke survivors with identifiable cut-off scores indicating major and/or any mood disorder in at least one study were selected and clinical utility was assessed. Those with high clinical utility (against predefined criteria) were selected for recommendation. RESULTS: Thirty papers examining 27 screening tools were identified and 16 tools met the psychometric and clinical utility criteria: 10 were verbal self-report tools, four were observational and two incorporated visual prompts for those with communication problems. Only the Stroke Aphasic Depression Questionnaire -Hospital version (SADQ-H) met all the psychometric and utility criteria. The nine-item Patient Health Questionnaire (PHQ-9) can detect major depression and the 15-item Geriatric Depression Scale (GDS-15) can identify milder symptoms; both are feasible to use in clinical practice. The Hospital Anxiety and Depression Scale (HADS) was the only tool able to identify anxiety accurately, but clinical utility was mixed. CONCLUSIONS: Valid and clinically feasible mood screening tools for stroke have been identified but methodological inconsistency prevented recommendations about the optimal cut-off scores.

A comparison of three strains of holstein-friesian grazed on pasture and managed under different feed allowances.

This experiment compared Holstein-Friesian (HF) cows of New Zealand (NZ) origin representative of genetics present in the 1970s (NZ70; n = 45) and 1990s (NZ90; n = 60), and a group of HF cows of North American origin with 1990s genetics (NA90; n = 60), which were managed in grazing systems with a range of feeding allowances (4.5 to 7.0 t/cow per yr) over 3 yr. The NZ70 cows had the lowest Breeding Worth genetic index and the lowest breeding values for yields of fat, protein, and milk volume; the NZ90 and NA90 cows were selected to have similar breeding values for milk traits and were representative of cows of high genetic merit in the 1990s. The NZ90 cows had a higher milk protein concentration (3.71%) than either the NA90 (3.43%) or the NZ70 cows (3.41%), and a higher milk fat concentration (4.86%) than the NA90 cows (4.26%) with a level similar to the NZ70 cows (4.65%). The NZ90 cows produced significantly greater yields of fat, protein, and lactose than the NA90 and NZ70 cows. The NZ70 cows had the lowest mean annual body weight (473 kg) but the highest body condition score (BCS; 5.06). Days in milk were the same for the 2 NZ strains (286 d in milk), both of which were greater than the NA90 cows (252 d in milk). There was no genotype x environment interaction for combined milk fat and protein yield (milksolids), with NZ90 producing 52 kg/cow more than the NA90 at all feeding levels. The NZ70 strain had the highest seasonal average BCS (5.06), followed by the NZ90 (4.51) and the NA90 (4.13) strains on a 1 to 10 scale. Body condition score increased with higher feeding levels in the 2 NZ strains, but not in the NA strain. The first-parity cows commenced luteal activity 11 d later than older cows (parities 2 and 3), and the NA90 cows commenced luteal activity 4 and 10 d earlier than the NZ70 and NZ90 cows. Earlier estrus activity did not result in a higher in-calf rate. The NZ70 and NZ90 cows had similar in-calf rates (pregnancy diagnosed to 6 wk; 69%), which were higher than those achieved by NA90 cows (54%). Results showed that the NA90 strain used in this experiment was not suitable for traditional NZ grazing systems. Grazing systems need to be modified if the NA90 strain is to be successfully farmed in NZ. The data reported here show that the NA90 cows require large amounts of feed, but this will not prevent them from having a lower BCS than the NZ strains. Combined with poor reproductive performance, this means that NA90 cows are less productive than NZ HF in pasture-based seasonal calving systems with low levels of supplementation.

A comparison of three strains of Holstein-Friesian cows grazed on pasture: growth, development, and puberty.

With the introduction of a protein milk payment system in New Zealand in 1988, there was an influx of North American (NA) Holstein-Friesian (HF) genetics into New Zealand (NZ) dairy herds, leading to an increase in the average percentage of NA genetics in NZ HF cows--from 2% in 1980 to 38% in 1999. Of interest has been the effect this change has had on farm profitability and on the management required for these animals, as well as the phenotypic changes that have occurred within the national herd under the breeding programs operated in NZ from 1970 to 1990. The objective of this study was to quantify differences in body dimensions, body weights, and puberty-related parameters among 3 strains of HF, representing animals of NZ origin representative of the genetics present in 1970 and 1990 and of NA origin with 1990s genetics. A total of 172 animals born in 1999 were compared. The strains were 1) NZ70, a strain of NZ Friesian (average 7% NA genetics) equivalent to high-genetic-merit (high Breeding Worth) cows farmed in the 1970s; 2) NZ90, a strain of HF of NZ origin (average 24% NA genetics) typical of the animals present in the 1990s; and 3) NA90, a strain of HF of NA origin (average of 91% NA genetics) typical of animals present in the 1990s. The differences in BW among all strains were significant at 6 and 12 mo of age. At 15 and 24 mo, the 2 NZ strains were significantly lighter than the NA90 animals. At 24 mo of age (i.e., prior to first calving), the NA90 strain animals (BW = 515 kg) were 22 and 34 kg heavier than the NZ90 and NZ70 strains. The body length of the NA90 strain was greater than either of the 2 NZ strains; the differences among the NA90 strain and the 2 NZ strains varied from 2 to 6 cm, with the differences generally being greater at older ages. The trend in heart girth difference among strains was similar to that observed for body length. The wither height of the NA90 animals was greater than that of the NZ strains by 1 to 7 cm, although there was no significant difference between the NA90 and NZ90 strains at birth. At puberty the NA90 heifers were 20 d older and 20 kg heavier than the NZ90 heifers, which in turn were 25 kg and 25 d older than the NZ70 heifers. The NA90 strain had a heavier mature body weight, and their older age at puberty suggested either that they mature later or that, under pastoral conditions, their growth rate is limited by their inability to consume sufficient metabolizable energy as grazed pasture, with a consequent delay in puberty. Results from this study will be useful in revising target BW in growing heifers of different germplasm.

Devices to improve coronary artery bypass grafting (CABG) surgery.

As off-pump coronary artery bypass grafting becomes the method of choice for cardio-thoracic surgeons, it has become apparent that the facilitation of coronary artery anastomosis on a beating heart needs to be addressed by improved instrumentation. We propose an intraluminal anastomosis device used in conjunction with a biologic-glue to eliminate suturing and serve as a scaffold for constructing stable anastomoses. The device will continue to serve as an eluting stent postoperatively. The simple technique of using the device and the adhesive will require 5 minutes or less for anastomosis. Moreover, we introduce a novel parallel port vacuum stabilizer foot equipped with a uniform lateral tension inducing turnbuckle mechanism to be used with off-pump stabilization systems. A proposed in vitro protocol details using saphenous vein segments and coronary arteries to test the patency of multiple end-to-side grafts. A pressure transducer will be attached to the graft to monitor flow characteristics. An in vivo protocol details construction of anastomoses during off-pump coronary artery bypass grafting in pigs using the anastomosis device, the turnbuckle vacuum foot, and the biologic-glue. Anastomosis patency will be evaluated intraoperatively and one month postoperatively. Furthermore, the graft site will be examined via flow measurement, angiography, and histological analysis.

Selective expression of prion protein in peripheral tissues of the adult mouse.

The level of expression of normal cellular prion protein, PrP(c) (cellular prion protein), controls both the rate and the route of neuroinvasive infection, from peripheral entry portal to the CNS. Paradoxically, an overview of the distribution of PrP(c) within tissues outside the CNS is lacking. We have used novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue (in order to optimise immunohistochemical labelling of this conformationally labile protein), in combination with in situ hybridisation, to examine the expression of PrP(c) in peripheral tissues of the adult mouse. We found that although prion protein is expressed in many tissues, it is expressed at high levels only in discrete subpopulations of cells. Prominent amongst these are elements of the "hardwired neuroimmune network" that integrate the body's immune defence and neuroendocrine systems under CNS control. These prion protein-expressing elements include small diameter afferent nerves in the skin and the lamina propria of the aerodigestive tract, sympathetic ganglia and nerves, antigen presenting and processing cells (both follicular and non-follicular dendritic cells) and sub-populations of lymphocytes particularly in skin, gut- and bronchus-associated lymphoid tissues. Prion protein is also expressed in the parasympathetic and enteric nervous systems, in the dispersed neuroendocrine system, and in peripheral nervous system axons and their associated Schwann cells. This selective expression of cellular prion protein provides a variety of alternative routes for the propagation and transport of prion infection entering from peripheral sites, either naturally (via the aerodigestive tract or abraded skin) or experimentally (by intraperitoneal injection) to the brain. Key regulatory cells that express prion protein, and in particular enteroendocrine cells in the mucosal wall of the gut, and dendritic cells that convey pathogens from epithelial layers to secondary lymphoid organs, may be particularly important in the transmission of infection in the periphery.

A marked disparity between the expression of prion protein and its message by neurones of the CNS.

Expression of the normal cellular form of prion protein is both necessary and rate-limiting in the spread of prion disease, yet its cellular expression in vivo is poorly understood. To optimise immunohistochemical labelling of this protein in mouse brain, we have developed novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue. Expression was found to be predominantly neuronal, and to differ between different classes of neurone. Thus, neurones immunoreactive for GABA expressed very high levels of normal prion protein; most projection neurones expressed much lower levels, particularly on their axons in the major fibre tracts, and some neurones (e.g. those positive for dopamine) displayed no detectable prion protein. In marked contrast, all neurones, even those that were immunonegative, expressed high levels of message for prion protein, shown by non-radioactive in situ hybridisation. Glia expressed very low levels of message, and undetectable levels of prion protein. We conclude that the steady-state level of prion protein, which differs so markedly between different neuronal types, is primarily controlled post-transcriptionally, possibly by differences in protein trafficking or degradation. These marked differences in the way different neurones produce and/or degrade their normal cellular prion protein may influence the selective spread and neurotoxic targeting of prion diseases within the CNS.

Progesterone and follicular changes in postpartum noncyclic dairy cows after treatment with progesterone and estradiol or with progesterone, GnRH, PGF2alpha, and estradiol.

A previous study showed that noncyclic dairy cows treated with 10 microg of GnRH and a progesterone-releasing CIDR insert on Day 0, 25 mg of PGF2alpha and CIDR removal on Day 7, followed by 1 mg estradiol benzoate on Day 9 for those cows that still had not shown estrus (CGPE program) had higher conception rate (47% vs. 29%) than cows treated only with CIDR and estradiol benzoate as above (CE program). This study was to investigate the mechanisms by which the CGPE program improved conception rate compared with the CE program. Sixteen noncyclic Holstein-Friesian cows were randomly assigned to 2 groups balanced for the size and growth pattern of the dominant follicles, which were determined by ultrasonography over a 3-d period. One group received the above CGPE treatment, and the other group received the CE treatment. Follicular and luteal development were monitored by daily ultrasonography. Blood samples were collected daily from Day -2 to Day 11, and thereafter milk samples were collected thrice weekly for a further 24 d. Blood and milk samples were analyzed for progesterone. The GnRH treatment induced ovulation in 7 of 8 cows, resulting in elevated (P<0.05) progesterone concentrations between Days 4 and 7 for cows in the CGPE group. All induced CL underwent luteolysis by 24 h after PGF2alpha treatment. Within 5 d of CIDR removal, 7 of 8 cows in both the CE and CGPE groups ovulated. The interval from emergence of the ovulatory follicle to ovulation was similar (P=0.32) but less (P<0.05) variable for the CGPE group (9.0+/-0.3 d) compared with the CE group (10.3+/-1.2 d). Progesterone concentration in milk samples was similar between the two groups up to 10 d after ovulation. In summary, the GnRH treatment induced ovulation or turnover of dominant follicles, induced a synchronized initiation of a new follicular wave, and increased the progesterone concentration from 4 d after treatment. These could be the reasons for the increased conception rate of cows treated with the CGPE program.

Treatment of noncyclic lactating dairy cows with progesterone and estradiol or with progesterone, GnRH, prostaglandin F2 alpha, and estradiol.

The efficacy of two programs for treating noncyclic cows was compared. In trial 1, 478 cows in five herds were randomly divided into two groups. Cows in one group (C group) were treated with an intravaginal progesterone device for 8 d followed in 48 h by 1 mg of estradiol benzoate to cows that had not been detected in estrus since device removal. Those in the other group (CGP group) were treated with progesterone and estradiol as for the C group plus 10 micrograms of a GnRH agonist (buserelin) at device insertion and 25 mg of PGF2 alpha 7 d after device insertion. In trial 2 with 729 cows in nine herds, the treatments were similar to those in trial 1 except that the duration of progesterone treatment was 7 d. No significant difference was found between trials and results from both trials were combined. Compared with C group cows, CGP group cows had a greater estrous response rate (93.2 vs. 89.1%), a greater conception rate to first artificial insemination (AI, 47.1 vs. 29.4%), marginally lower conception rate to second AI (52.9 vs. 59.7%), lower nonpregnancy rate (8.3 vs. 11.1%), and shorter intervals from the start of breeding to conception by AI (9.8 vs. 15.3 d) or by AI or natural mating (21.6 vs. 26.3 d). The treatment protocol used for the CGP group achieved better reproductive performance than that used for the C group.

Estrus synchronization of lactating dairy cows with GnRH, progesterone, and prostaglandin F2 alpha.

The reproductive performance of synchronized cows was compared with that of nonsynchronized cows. In trial 1, cyclic cows in five seasonal herds were randomly divided into two groups. Cows in one group (n = 515) were treated with a GnRH agonist and an intravaginal progesterone device, followed in 7 d by a PGF2 alpha injection, and the device was removed 1 d after PGF2 alpha. Cows in the other group (n = 512) did not receive any treatment and acted as control. In trial 2, the treatments were similar to those used in trial 1 except that the progesterone device was removed at the time of PGF2 alpha injection (synchronized: n = 516; control: n = 512). The estrus synchronization rate was 92.8% in trial 1 and 92.2% in trial 2. Conception rate to first artificial insemination (AI) was lower for synchronized cows than for control cows in trial 1 (56.5 vs. 62.7%), but similar in trial 2 (64.6 vs. 63.3%). Across both trials, the pregnancy rate during the AI breeding period was greater for the synchronized cows (85.6%) than for the control cows (81.2%). The synchronization treatment reduced the interval from start of the breeding season to conception for cows conceiving by AI (8.9 vs. 14.8 d) or by AI or natural mating (14.1 vs. 21.6 d). The synchronization protocol used in trial 2 achieved better conception rate than that used in trial 1, but the precision of estrus was less in trial 2 than in trial 1.

The reproductive performance of anoestrous dairy cows following treatment with progesterone and oestradiol prior to the start of mating.

AIMS: To determine the reproductive performance of cows diagnosed as anoestrus prior to the planned start of mating (PSM) when they were either treated when first diagnosed, or left untreated until 16 days after the PSM. METHODS: A clinical trial was conducted during the 1996/97 and 1997/98 breeding seasons involving 823 anoestrous dairy cows in 14 herds. On Day -8 (PSM = Day 0), cows in one group (Treated) were each treated with an intravaginal device containing 1.9 g of progesterone (CIDR). The CIDR device was removed on Day -2, and on Day -1 each cow was injected intramuscularly with 1 mg oestradiol benzoate. Cows in the second group (Control) remained untreated at the time of first examination. All cows detected in oestrus after the PSM were mated by artificial insemination (AI) or a bull. Sixteen days after the PSM, all cows that had not been mated were presented for veterinary examination, and those which were still classified as anoestrus were treated with the previously described CIDR regimen. Pregnancy status and approximate date of conception were determined by palpation per rectum 10 -13 weeks after the PSM or 6 weeks after the end of the mating period. RESULTS: Treatment of anoestrous cows 8 days before the PSM significantly increased the number of cows detected in oestrus (95.0% vs 63.1%; p<0.001) and conceiving (59.5% vs 38.8%; p<0.001) during the first 21 days of mating, and reduced the interval from PSM to conception by 7.5 days (p<0.001). There was no significant difference between the conception rate of cows mated following the CIDR treatment regimen compared to cows mated at their first spontaneous oestrus after calving (52.4% vs 58.3%; p = 0.143). CONCLUSION: Diagnosis and treatment of anoestrous dairy cows prior to the start of mating significantly improves their reproductive performance under the seasonal mating conditions typical of spring-calving New Zealand dairy herds.

Reproductive performance of dairy heifers after estrus synchronization and fixed-time artificial insemination.

The reproductive performance of heifers after estrus synchronization and fixed-time AI was compared with nonsynchronized heifers in 25 spring-calving herds. Within herds, heifers were divided into a synchronized (n = 1123) or a control (n = 1125) group. Heifers in the synchronized group were treated with a combination of progesterone, estradiol benzoate, and PGF2 alpha and were inseminated between 50 and 54 h after progesterone treatment. Returns to first service were resynchronized with progesterone treatment between 16 and 21 d after the fixed-time AI. The conception rate of synchronized heifers to the fixed-time AI (53.2%) and to AI after resynchronization (53.1%) was lower than that of control heifers (63.7%). However, pregnancy rate in the first 24 d was higher for the synchronized group (72.4%) than for the control group (67.8%). More control heifers (5.7%) than synchronized heifers (4.0%) failed to conceive. The interval from start of breeding to calving was earlier for synchronized (296.2 d) than for control (299.5 d) heifers. Jersey heifers had lower reproductive performance than did Friesian heifers. Synchronized heifers gave birth to more female calves (53.8%) than did control heifers (45.7%). It is concluded that the above program can be used successfully to synchronize dairy heifers for fixed-time AI.

Effects of oestrus synchronisation and fixed-time artificial insemination on the reproductive performance of dairy heifers.

AIM: To compare the reproductive performance of heifers after oestrus synchronisation and fixed-time artificial insemination with non-synchronised heifers bred by herd sires. METHODS: Heifers from 10 spring-calving herds were randomly divided into two groups by herd, breed and age. Heifers in one group (the synchronised group, n = 478) were synchronised with a combination of progesterone, oestradiol benzoate and PGF2alpha, and inseminated 50-54 hours after progesterone treatment. Returns to first service were resynchronised with progesterone treatment 16-21 days after the fixed-time artificial insemination. Heifers in the other group (the control group, n = 470) did not receive any treatment and were bred by herd sires. RESULTS: The conception rate of synchronised heifers to the fixed-time artificial insemination was 51.2% and to the artificial insemination after resynchronisation 40.4%. The pregnancy rate at the end of the breeding season was lower (p<0.001) for the synchronised (92.9%) than for the control (97.2%) group. The interval from start of breeding to calving was earlier for synchronised (295.9 +/- 22.5 days, mean +/- s.d.) than for control (298.5 +/- 17.3 days) heifers. CONCLUSION: Results from this study indicate that the oestrus synchronisation programme used in the present study can reduce reproductive performance by increasing the empty rate compared with natural mating.

Estrus detection using radiotelemetry or visual observation and tail painting for dairy cows on pasture.

The efficiency and accuracy of estrus detection using HeatWatch (DDx Inc., Denver, CO) or visual observation were compared in an autumn-calving Friesian herd (n = 48 per group) and a spring-calving Jersey herd (n = 50 per group) grazing on pasture. Cows in the group monitored by the HeatWatch system were fitted with a pressure-sensitive transmitter that signaled mounting activities associated with estrus. Visual observation was carried out for about 20 min before the morning and afternoon milkings and was aided by a strip of paint applied over the tailhead. Ovarian cyclicity was monitored with progesterone concentrations in milk samples collected twice a week. The efficiency and accuracy of estrus detection were, respectively, 98.4 and 97.6% for visual observation and 91.7 and 100% for HeatWatch detection. Autumn-calving herds differed from spring-calving herds in duration of estrus (9.7 vs. 7.3 h), number of mounts (13.6 vs. 8.5), total duration of mounts (36.8 vs. 19.9 s), and mean duration of a mount (2.6 vs. 2.3 s). There was no significant variation in the distribution of the time of onset of estrus or mounting activities at different hours of the day. Conception rate was similar for AI after estrus detection with HeatWatch (65.8%) or after visual observation (65.0%). The highest conception rate was obtained when AI was carried out between 12 and 18 h after the first mount. Both the HeatWatch system and visual observation plus tail painting can be used for estrus detection of dairy cows on pasture.

Pseudoparalysis of the lower extremity in an infant.

We describe a case of septic arthritis of the knee in an afebrile, well-appearing four-month-old female. She had been evaluated previously for lower extremity disuse attributed to antecedent trauma. Her physical examination was remarkable only for limitation of extension of the affected leg at the knee. Emergency physicians should understand the physical examination findings suggesting joint effusion and the need to consider osteomyelitis/septic arthritis in children less than one year of age with pseudoparalysis.

Synchronization of estrus with PGF2 alpha administered 18 days after a progesterone treatment in lactating dairy cows.

In a previous study we showed that estrus synchronization with 2 treatments of PGF2 alpha 13 d apart reduced conception rate at the synchronized estrus and that this reduction occurred mainly in cows in the early luteal phase at the second PGF2 alpha treatment. The objective of the present study was to determine the efficacy of a synchronization regimen in which PGF2 alpha was administered during the mid- to late-luteal phase to cows that had previously been synchronized with progesterone. Spring-calving cows from 6 dairy herds were used in this study. On Day -32 (Day 1 = the start of the breeding season), cows that had calved 2 or more weeks ago were randomly assigned to a synchronization (S, n = 732) or control (C, n = 731) group. Cows in Group S were treated with an intravaginal progesterone device (CIDR) for 12 d from Day -32 to Day -20, while those in Group C were left untreated. Similar percentages of cows in Group S (80.6%) and C (82.9%) had cycled by Day -7. The CIDR treatment synchronized the onset of estrus, resulting in 92.9% of cows in estrus being detected within 7 d after CIDR removal. Cows in Group S that had cycled by Day -7 were treated with PGF2 alpha (25 mg, i.m., Lutalyse) on Day -2. Cows in both groups that were anestrous on Day -7 were treated with a combination of progesterone and estradiol benzoate (EB) to induce estrus and ovulation (CIDR and a 10 mg EB capsule on Day -7, CIDR removal on Day -2, and injection of 1 mg EB 48 h after CIDR removal). The PGF2 alpha treatment synchronized the onset of estrus in 87.5% of the cows. Group S and C cows had similar conception rates to first (61.0 vs 58.3%) and second (58.4 vs 60.9%) AI; similar pregnancy rates over the AI period (82.8 vs 79.2%) and over the whole breeding season (91.9 vs 90.6%); and required a similar number of services per pregnancy to AI (1.7 vs 1.8). The interval from the start of the breeding season to conception for cows conceiving to AI or to combined AI and natural mating was shorter (P < 0.001) by 5.7 and 6.2 d, respectively, for the Group S cows. It is concluded that the treatment regimen tested in the present study achieved satisfactory estrus synchronization, had no detrimental effect on fertility at the synchronized estrus, and shortened the interval from start of the breeding season to conception.

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.

Headache etiology in a pediatric emergency department.

BACKGROUND: Headache may be the presenting complaint of serious diagnoses such as meningitis, brain tumor, or shunt malfunction, yet no previous studies have examined the spectrum of diagnoses for the pediatric emergency department (ED) population with a chief complaint of headache. METHODS: In 1993, 53,988 visits were made to the ED of an urban children's hospital. Six hundred ninety-six patients (1.3%) had a chief complaint of headache. Half of these visits, distributed randomly throughout the year, were chosen for review; total sample size was 288. RESULTS: Patient age ranged from two to 18 years (2-5 years, 24.3%; 6-12 years, 57.6%; 13-18 years, 18.1%). The spectrum of ED diagnoses included viral illness (39.2%), sinusitis (16.0%), migraine (15.6%), post-traumatic headache (6.6%), streptococcal pharyngitis (4.9%), and tension headache (4.5%). No cases of brain tumor or bacterial meningitis were identified at the time of ED visit. The only serious neurologic conditions diagnosed were 15 cases of viral meningitis (5.2%), one shunt malfunction, one newly diagnosed hydrocephalus, one Burkitt's lymphoma patient with newly diagnosed CNS infiltration, and one punctate hemorrhage post head trauma. Two thirds of patients had radiologic and/or laboratory tests. Positive findings were as follows: 45.6% of sinus radiographs, 16.3% of rapid streptococcal antigen tests, 60.9% of lumbar punctures, and 19.0% of brain imaging studies. The frequency of serious and nonserious conditions as a cause of headache was compared to data from general EDs. CONCLUSION: Serious conditions presenting with the chief complaint of headache in the pediatric ED were not common in our population. The most frequent diagnoses in our review were viral illness, sinusitis, and migraine, in contrast to adult studies in which tension headache and migraine were most common. Only 6.6% of patients had serious neurologic diagnoses, which is in the range reported for general EDs. Of the serious conditions in our study, 80% were viral meningitis.

Treatment of post-partum anoestrous dairy cows with progesterone, oestradiol and equine chorionic gonadotropin.

Anoestrus in lactating dairy cows at the start of the breeding season is a major form of reproductive wastage for seasonal dairy production based on pasture. The objective of this study was to compare the reproductive performance of anoestrous cows that were treated with a combination of progesterone, oestradiol and equine chorionic gonadotrophin either 10 days before (T-10, n = 2 19) or 16 days after (T+16, n = 229) the start of the breeding season. A higher percentage of cows in the T-10 group were detected in oestrus and inseminated during the first 6 days of breeding than those in the T+16 group (69.4% v. 26.2%. p <0.001). However, the percentage of cows detected in oestrus by Day 16 was similar between the two treatment groups (T10 v. T+ 16; 77.7% v. 76.7%). There was no difference between treatment groups in conception rate to the first (51.2% v. 59.0%) or the second insemination (50.8% v. 57.6%), in pregnancy rate over the first 49 days (74.0% v. 75.1%), in empty rate (10.0% v. 10.5%) or in the mean day of conception from the start of the breeding season (24.0 v. 25.7 days). These results suggest that, under favourable environmental conditions, treatment of anoestrous cows with the programme used in this trial can be performed 16 days after the start of the breeding season with similar results to that performed 10 days before the start of the breeding season. Further studies are needed to determine if this is the case under different environmental conditions or for other treatment programmes.