Associations between postpartum phenotypes, cow factors, genetic traits, and reproductive performance in seasonal-calving, pasture-based lactating dairy cows.

The objective of this study was to evaluate associations between corpus luteum (CL) status, uterine health, body condition score (BCS), metabolic status, parity, genetic merit for fertility traits, and reproductive performance in pasture-based dairy cows managed for seasonal reproduction. First- and second-lactation (n = 2,600) spring-calving dairy cows from 35 dairy farms located in Ireland were enrolled in the study. Farms were visited every 2 wk, and animals that were at wk 3 (range: 14-27 d in milk) and wk 7 (range: 42-55 d in milk) postpartum were examined. Body condition score was measured using a 1-to-5 scale in 0.25-point increments. Transrectal ultrasound examination was performed at wk 3 and 7 postpartum to determine presence or absence of CL and ultrasound reproductive tract score (scale of G1-G4). Blood samples were collected at each visit, and the concentrations of glucose, ß-hydroxybutyrate (BHB), and fatty acids (FA) were analyzed using enzymatic colorimetry. Animals were grouped into 3 BCS categories [low (≤2.5), target (2.75-3.25), and high (≥3.5)], 2 CL categories (present or absent), 2 uterine health status categories (normal or abnormal), and 3 metabolic status categories [good (high glucose, low FA and BHB), poor (low glucose, high FA and BHB), and moderate (all other combinations)]. Fisher's exact test was used to test for associations between variables and was supplemented by logistic regression. More cows with a CL at wk 7 were served during the first 21 d of the breeding period compared with cows without a CL. Cows classified as having a uterine score of G3 or G4 at wk 3 and 7 had lower odds of pregnancy establishment during the breeding period compared with animals with a uterine score of G1 or G2. Animals with low BCS at wk 7 had lower odds of pregnancy establishment than cows with a target BCS. Cows classified as having good metabolic status at both wk 3 and wk 7 had greater odds of pregnancy establishment during the first 21 d of the breeding season than those classified as having poor metabolic status. Overall, primiparous cows had greater reproductive performance than second-parity cows. Animals in the quartiles with the best predicted transmitting ability for survival and calving interval had better reproductive performance compared with animals in the other quartiles. Cows that had better genetic merit for fertility traits and good metabolic status, achieved target BCS, and had a favorable ultrasound reproductive tract score and a CL present at wk 7 postpartum had superior reproductive performance.

Effect of altering the type of dietary carbohydrate early postpartum on reproductive performance and milk production in pasture-grazed dairy cows.

The objective of this study was to assess the effect of increasing dietary starch for approximately 30 d postpartum on reproduction outcomes in pasture-grazed, seasonal-calving dairy cows. Cows (n = 948) from 3 commercial herds were blocked by age (2, 3, and >3 yr), breed, and expected calving date and randomly assigned to 1 of 2 postpartum treatment groups: high starch (34.7 ± 1.9% nonstructural carbohydrate; mean ± SD) or low starch (22.5 ± 0.4% nonstructural carbohydrate). The high-starch group in all 3 farms received 4.0 to 4.5 kg/d of a 75:25 cracked corn:barley grain mixture in the dairy parlor, split evenly between the morning and afternoon milkings. The low-starch cows received 5.0 to 5.5 kg/d of a 50:50 mixture of palm kernel meal:soy hulls (herds 1 and 3) fed in the parlor; low-starch cows in the remaining herd (herd 2) did not receive a concentrate feed. Cows were cograzed on ryegrass-white clover dominant pastures and were offered corn silage (herds 1 and 3) and canola, corn distillers grain, and palm kernel meal (herd 1) throughout the study. At 1 mo before the start of the seasonal breeding period, the high-starch supplement was removed, and within each herd treatment groups were managed similarly through breeding. Presence of purulent vaginal discharge was assessed at 28 DIM, and tail paint was assessed weekly from 2 to 6 wk postpartum for signs of estrus. The interval to first observed estrus was unaffected by treatment (32.7 vs. 33.5 ± 2 d for high and low starch, respectively), but there were tendencies for a herd × treatment interaction for proportion of cows pregnant to first service and for pregnancy within 6 wk. This interaction was significant for the proportion of cows finally pregnant; a lower proportion of high-starch cows were pregnant to first service, pregnant by 6 wk, and pregnant by the end of the seasonal breeding period in herd 1, but diet did not affect these outcomes in the other herds. Our results do not support a positive effect on reproduction from increasing dietary starch in seasonally bred grazing dairy cows. However, the interactions indicate variability in the herd response to dietary starch early postpartum and imply that pregnancy rate could potentially be compromised through the provision of starch to grazing dairy cows in early lactation (i.e., prebreeding). The experiment was not designed to define the reasons for these interactions, but differences should be considered in future research on the subject.

Donepezil provides positive effects to patients treated with gabapentin for neuropathic pain: an exploratory study.

BACKGROUND: The first-line medication gabapentin and the acetylcholinesterase inhibitor donepezil represent a new promising combination to improve treatment outcomes for patients with severe neuropathic pain. The drugs have previously shown synergism following co-administration in nerve-injured rats. METHODS: The clinical relevance of adding donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The study comprised two consecutive periods of minimum 6 weeks: (1) titration of gabapentin to the highest tolerable dose or maximum 2400 mg daily, and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events. Pain scores were also analysed using mixed-effects analysis with the software NONMEM to account for intersubject variability. RESULTS: Eight patients commenced treatment with donepezil, of which two withdrew because of adverse events. Addition of donepezil resulted in clinically relevant reductions of pain (> 11 units on a 0-100 scale) and improved mental wellness in three of six patients. The remaining three patients had no obvious supplemental effect. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (P < 0.0001 combination vs. monotherapy). CONCLUSION: Donepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. The promising results support controlled clinical trials of the drug combination. The usefulness of mixed-effects analysis in small-scale trials and/or for data with high intersubject variability was also demonstrated.

Effect of grass dry matter intake and fat supplementation on progesterone metabolism in lactating dairy cows.

Progesterone (P4) metabolism in dairy cattle can be manipulated by alterations in dry matter intake and diet composition. Our objectives were to determine the effects of grazing allowance and fat supplementation on P4 metabolism in lactating dairy cows. Forty mid- to late-lactation Holstein-Friesian dairy cows were used in a completely randomized block design, with a 2 × 2 factorial arrangement of treatments. Cows were assigned to receive 1 of 2 pasture allowances (ad libitum allowance [AL], 9.5 kg dry matter per day, or restricted allowance [R] 7 kg dry matter per day) and 1 of 2 fat supplementation treatments (750 g per day saturated fat [F] or no fat supplement [NF]). All cows received an additional 4 kg per day of concentrate. Grass dry matter intake (GDMI) was measured 5 wk after the initiation of dietary treatment. Cows were treated with prostaglandin F(2α) (PGF(2α)) to eliminate the endogenous source of P4, and two intravaginal progesterone-releasing devices (CIDR) were inserted into each cow for a period of 8 days. Regular blood samples were taken before and after the removal of the intravaginal progesterone-releasing devices, and analyzed for P4 concentrations. The half-life (t½) and metabolic clearance rate (MCR) of P4 was calculated for each cow. There was no effect of GDMI or fat supplementation on the t½ or MCR of P4. There was a tendency for an interaction between GDMI and fat supplementation on the t½ of P4; cows on the restricted-F diet tended to have a longer P4 t½ than cows on the ad libitum-F diet. It was concluded that greater alterations in GDMI than achieved in the current study are required to change P4 metabolism. A combination of fat supplementation and restricted feeding slows P4 clearance, which may have beneficial implications for fertility.

The effect of strategic supplementation with trans-10,cis-12 conjugated linoleic acid on the milk production, estrous cycle characteristics, and reproductive performance of lactating dairy cattle.

The objective was to determine the effects of a protected (lipid-encapsulated) conjugated linoleic acid (LE-CLA) supplement on milk production, estrous cycle characteristics, and reproductive performance in lactating dairy cows on a pasture-based diet. Spring calving dairy cows (n=409) on a single pasture-based commercial dairy farm were used in a completely randomized block design. Cows were assigned to 1 of 2 dietary supplements [LE-CLA (n=203) or no supplement (control, n=206)]. The LE-CLA cows received 51 g/d of a lipid supplement containing 5 g of both trans-10,cis-12 and cis-9,trans-11 CLA from 0 to 60 d in milk. Milk samples were collected 3 times weekly, and each sample was analyzed for progesterone to determine the interval to first ovulation and estrous cycle characteristics. Milk yield and concentrations of fat, protein, and lactose were measured every 2 wk. Cows were inseminated following visual observation of estrus. The breeding season commenced on April 8, 2009 and continued for 16 wk. Transrectal ultrasonography was carried out at 30 to 36 d and 60 to 66 d post-AI to diagnose pregnancy. The LE-CLA treatment resulted in a decrease in milk fat concentration (36.9±0.06 g/kg vs. 30.7±0.06 g/kg for control and LE-CLA, respectively) and yield (0.91±0.02 kg/d vs. 0.84±0.02 kg/d for control and LE-CLA, respectively); however, milk yield was increased by LE-CLA supplementation (24.7±0.7 kg/d vs. 27.2±0.7 kg/d for control and LE-CLA, respectively), resulting in no overall difference in milk energy output. No effect of LE-CLA was observed on any estrous cycle characteristics or measures of reproductive performance. These results support that in pasture-based systems of dairy production, where energy intake limits milk production, energy spared by CLA-induced milk fat depression is partitioned toward increasing milk yield rather than toward body reserves.

Effect of supplementation with different fat sources on the mechanisms involved in reproductive performance in lactating dairy cattle.

Supplementary fat positively influences reproductive performance in dairy cattle, although the mechanisms involved are not clearly defined. Our objective was to determine the effects of four different fat supplements on follicle development, plasma steroid hormone concentrations and prostaglandin (PG) synthesis in lactating dairy cattle. Forty-eight early lactation Holstein-Friesian cows (21 primiparous, 27 multiparous) were used in a completely randomized block design. Cows were fed the same basal TMR diet and received one of four fat supplements: (i) palmitic acid (18:0 fatty acid; Control), (ii) flaxseed (rich in 18:3 n-3 fatty acid; Flax), (iii) conjugated linoleic acid (a mixture of cis-9, trans-11 and trans-10, cis-12 isomers; CLA), and (iv) fish oil (rich in 20:5 and 22:6 n-3 fatty acids; FO). All lipid supplements were formulated to be isolipidic; palmitic acid was added as necessary to provide a total lipid supplement intake of 500 g/day. Cows were synchronized to be in estrus on Day 15 of dietary treatment. All antral follicles were counted, and dominant follicles, subordinate follicles and corpora lutea were measured daily via transrectal ovarian ultrasonography for one complete estrous cycle. Blood samples were collected daily, and selected samples were analyzed for progesterone, estradiol, insulin-like growth factor-1, insulin, cholesterol and non-esterified fatty acids. Estrus was synchronized a second time, and liver and endometrial biopsies were collected on Day 7 of the estrous cycle. Gene expression was evaluated for a number of genes involved in prostaglandin synthesis (endometrium) and fatty acid uptake and utilization (liver). Fat supplementation had little effect on follicle development. Cows receiving supplementary n-3 fatty acids had lesser plasma progesterone (P4) and smaller corpora lutea than cows receiving the CLA or Control supplements. Effects of fat supplementation on the endometrial expression of genes involved in PG synthesis were minor. Hepatic expression of SREBF1, ASCL1 and FABP1 was reduced by FO supplementation. Reduced plasma P4 in n-3 supplemented cows may lead to a suboptimal uterine environment for embryo development and hence reduced fertility compared to cows receiving the control or CLA supplements.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. PATIENTS AND METHODS: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. RESULTS: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. CONCLUSION: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

Intra-arterial iodine-131-lipiodol for unresectable hepatocellular carcinoma.

BACKGROUND: Hepatic artery administration of iodine-131-Lipiodol serves as a modality that delivers targeted radiation therapy to hepatocellular carcinoma. Its efficacy has been promising according to trials conducted in the adjuvant setting after hepatic resection. Further investigation of its role in the palliative setting is warranted. METHODS: A retrospective review of 72 patients with unresectable hepatocellular carcinoma treated with iodine-131-Lipiodol and followed up by the St. George Hospital Sydney's hepatobiliary service was conducted. Efficacy of treatment was determined based on progression-free and overall survival as the endpoints using the Kaplan-Meier method. RESULTS: Sixty men and 12 women with a mean age of 65 years (standard deviation = 11) underwent iodine-131-Lipiodol treatment. Chronic viral hepatitis was present in 29 (41%) patients. Fifty (69%) patients were Child-Pugh class A. Median progression-free survival was 6 months, and overall survival was 14 months; the 1-, 2-, and 3-year survival rates were 52%, 33% and 20%, respectively. Factors associated with survival include the American Joint Committee on Cancer stage (P = .03), Barcelona Clinic Liver Cancer stage (P = .05), Cancer of the Liver Italian Program score (P = .008), tumor size (P = .01), extrahepatic disease (P < .001), previous surgery (P = .02), and response to treatment (P < .001). The response to treatment was identified through a multivariate analysis as the single independent predictor for survival (hazard ratio, 3.5; 95% confidence interval, 2.2-5.4; P < .001). CONCLUSIONS: Encouraging survival outcomes may be derived through administration of iodine-131-Lipiodol in patients with unresectable hepatocellular carcinoma. The overall success of treatment may be determined by the response to treatment.

The effect of dry period duration and dietary energy density on milk production, bioenergetic status, and postpartum ovarian function in Holstein-Friesian dairy cows.

Following parturition, it is typical for dairy cows to enter a period of negative energy balance and body condition loss to support mammary milk synthesis; this is associated with compromised reproductive performance. Alternative management strategies during the prepartum (dry) and early postpartum periods may ameliorate this loss. Forty mature Holstein-Friesian cows were assigned to 1 of 2 dry period treatments [standard 8-wk dry period (SDP) or no planned dry period (NDP)] and 1 of 2 dietary energy density treatments [standard TMR (STMR) or high-quality TMR (HTMR)]. Milk yield during wk 1 to 12 postpartum was reduced in cows assigned to the NDP treatment. Energy balance and body condition score (BCS) during wk 1 to 4 postpartum were increased in cows assigned to the NDP treatment compared with the cows assigned to the SDP treatment, and BCS increased from wk 5 to 12 postpartum in the NDP cows compared with the SDP cows. During the first 12 wk postpartum, cows assigned to the HTMR diet had greater milk yield and reduced milk fat concentration compared with the cows assigned the STMR diet. The BCS was greater from wk 5 to 12 postpartum in HTMR cows compared with STMR cows. During the period from wk -3 to +3 relative to parturition, circulating concentrations of insulin, glucose, and IGF-I were greater in cows in the NDP treatment compared with cows in the SDP treatment. Cows assigned to the HTMR diet had greater circulating insulin and glucose concentrations compared with the STMR cows from wk -3 to +3 relative to parturition. The first postpartum ovulation occurred earlier for cows in the NDP treatment compared with cows in the SDP treatment (16.9 vs. 24.8 d postpartum. Cows assigned to the STMR diet tended to have a higher conception rate to first service compared with cows assigned to the HTMR diet. Energy balance and metabolic status can be improved by either eliminating the dry period or by feeding a higher energy diet, but effects on the reproductive axis appear to be different.

Effect of offering rumen-protected fat supplements on fertility and performance in spring-calving Holstein-Friesian cows.

The objective of this study was to evaluate the effect of two different rumen-protected fat supplements, on reproductive performance and milk production, in grass-based spring calving cows. Two hundred and one Holstein-Friesian cows with an average lactation number of 3.6 (20% first lactation, 16% second lactation and 64% third lactation or greater) were grouped into blocks of three on the basis of calving date, lactation number and previous lactation milk yield for cows of second lactation or greater and on the basis of calving date for first lactation animals. From within-blocks individual animals were assigned at random, within 10 days post-calving, to one of the following three treatments: (1) Megalac Plus 3% (MP; 0.4kg/day, containing Ca salt of palm fatty acids and Ca salt of methionine hydroxy analogue), (2) Megapro Gold (MPG; 1.5kg/day, containing Ca salt of palm fatty acids, extracted rapeseed meal and whey permeate), and (3) Control (C; unsupplemented). Cows were supplemented for on average 103 days (range 54-134 days). The average milk yield over the first 12 weeks of lactation was higher (P<0.05) for both fat supplements compared to C and was higher for MP compared to C over the full lactation. Both supplements reduced (P<0.05) milk protein concentration over the first 6 weeks of lactation. MPG increased (P<0.05) conception rate to first service compared to C. Conception rate to first service was similar (P=0.14) on MP compared to C. For pregnancy to second service, C had a higher (P<0.05) conception rate than MP. There were no significant differences between treatments in overall pregnancy rate, services per conception, number of cows served in the first 3 weeks of the breeding season or the 6-weeks in-calf rate. Comparing the combined fat treatments to C resulted in a higher (P<0.05) conception rate to first service for the fat treatments but no significant difference in overall pregnancy rate. In conclusion, fat supplements increased conception rate to first service but did not significantly affect the proportion of cows pregnant at the end of the breeding season.

Referred sensations following stroke.

Referred sensations are recognized as phenomena experienced after amputation of a limb and have been used as proof of the consequences of changes in somatosensory body part representation in the adult brain. Such changes may accompany interruption of afferent sensory projections after subcortical stroke. This report describes some misplaced localization to touch in a subject 15 months after cerebral haemorrhage involving the posterior limb of the right internal capsule and lateral thalamus. The results revealed the occurrence of referred sensations, indicating some scrambling of the somatosensory representation of the affected limbs. While many stimuli were localized correctly, there were a number of stimuli applied to the hand and foot that were referred to more proximal limb segments. Stimuli to the upper arm were sometimes felt in more distal parts of the limb. Stimuli to the face were localized to the arm and not the hand. With the aim of determining consistency of findings, testing of the upper limb was carried out on four separate occasions. The subject had less referred sensations in each test, possibly indicating some change in his somatosensory representation that occurred with experience.

Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes.

Early steps of retroviral replication involve reverse transcription of the viral RNA genome and integration of the resulting cDNA copy into a chromosome of the host cell. The viral-encoded integrase protein carries out the initial DNA breaking and joining reactions that mediate integration. The organization of the active integrase-DNA complex is unknown, though integrase is known to act as a multimer, and high resolution structures of the isolated integrase domains have been determined. Here we use site-specific cross-linking based on disulfide bond formation to map integrase-DNA contacts in active complexes. We establish that the DNA-binding C-terminal domain of one integrase monomer acts with the central catalytic domain from another monomer at each viral cDNA end. These data allow detailed modeling of an integrase tetramer in which pairs of trans interactions link integrase dimers bound to substrate DNA. We also detected a conformational change in integrase- DNA complexes accompanying cleavage of the viral cDNA terminus.

Microleakage of three sealants following conventional, bur, and air-abrasion preparation of pits and fissures.

OBJECTIVES: The aim of this study was to compare the microleakage of a filled sealant with a drying agent (UltraSeal XT plus), a filled sealant (Prismashield) and an unfilled sealant (Delton), after conventional, bur, and air-abrasion tooth preparation techniques. SETTING: The study was completed in a clinical setting at the Simulated Practice Environment Clinic, School of Dentistry, University of Western Ontario, London, Ontario, Canada. SAMPLE AND METHODS: One hundred and eighty extracted teeth were cleaned and divided randomly into three groups. Group 1 was prepared using acid etch only. Group 2 was prepared with a 1/4 round bur in a low-speed handpiece followed by acid etching. Group 3 was prepared with high speed (120PSI) microabrasion using 27 microm alpha-alumina particles in a Midwest Airtouch unit. The teeth in each group were randomly assigned to one of the three subgroups according to the sealant applied. Subgroup A was sealed with a filled sealant with drying agent, B with a filled sealant only, and C with an unfilled sealant. All teeth were stored in artificial saliva for 7 days at 37 degrees C. After this, the teeth were coated with nail varnish 1 mm from the sealant and immersed in 1% methylene blue dye for 48 h at 37 degrees C. Each tooth was sectioned at four locations buccolingually and a total of 665 sections were ranked (0-3) for microleakage. Statistical analysis was completed using the Chi-squared test and Fisher's exact test. RESULTS: UltraSeal XT plus, the filled sealant with drying agent, showed significantly less microleakage than the other two sealants (P < 0.05). Delton, the unfilled sealant, showed significantly less microleakage than Prismashield, the filled sealant (P < 0.05). Air abrasion with acid etch showed significantly less microleakage than either bur with acid etch or acid etch alone. There was however, no significant difference between the bur and acid etch tooth preparations (P < 0.05). CONCLUSIONS: UltraSeal XT plus was the most effective sealant for preventing microleakage in this study. The most successful method of preparation was air abrasion with acid etch.

Current airway clearance techniques.

In recent times, airway clearance has become an increasingly important part of the treatment of patients with excessive bronchial secretions, especially those with cystic fibrosis. The number of airway clearance techniques available has also grown considerably, becoming increasingly more specific. This has allowed patients a greater choice of treatment techniques and has led to a subsequent rise in independence. This paper gives a brief overview of the methods of airway clearance currently being used by physiotherapists in New Zealand. To date, no one method has been shown to be more effective than another. It is imperative therefore, that those involved in respiratory care have a clear understanding of the airway clearance techniques available. This will allow us to provide out patients with the best possible treatment option.

Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization.

The study described in this report demonstrates that peripheral lymph nodes draining nonmucosal tissues can effectively serve as induction sites for the establishment of common mucosal immunity if the microenvironmental conditions are altered to mimic those normally present within mucosa-associated lymphoid tissues (e.g., Peyer's patches). Lymph node lymphocytes exposed in situ to the immunomodulatory influences of the hormone 1 alpha, 25-dihydroxy vitamin D 3 were found to produce less gamma interferon and interleukin-2 (IL-2) and far more IL-4, IL-5 and IL-10 than lymphocytes from control animals. When couples with vaccination with hepatitis B surface antigen (HBsAg), the hormone, immunomodulated switch from a peripheral lymph node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response. This was determined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal and oral secretions only in the hormone-treated animals. In addition, specific antibody-secreting cells were detectable in the lamina propria of the lungs and small intestines of the hormone-treated animals subsequent to vaccination, indicating that the homing properties of antigen-specific B cells were being affected by the treatment procedure. The humoral and mucosal immune responses were further augmented if both 1 alpha, 25-dihydroxy vitamin D 3 and dehydroepiandrosterone were used together as hormonal immunomodulators. This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens.

Event-related potentials--neurophysiological tools for predicting emergence and early outcome from traumatic coma.

OBJECTIVE: To determine the prognostic value of multimodal evoked potentials (EPs) and event-related (ERPs) potentials in coma (Glasgow Coma Score <8), after severe traumatic brain injury (TBI). DESIGN: Prospective, longitudinal study of neurophysiological responses recorded during traumatic coma. SETTING: Intensive Care Unit, Frenchay Hospital, Bristol, UK. PARTICIPANTS: Fifty-four comatose TBI patients (age range 1-80 years, mean 36.4). METHODS: Neurophysiological responses were recorded from 11 scalp electrodes with earlobe reference. Conduction times were measured for brainstem auditory, flash visual and somatosensory, short-latency EPs. Peak latencies and amplitudes were determined for long-latency components of visual and auditory ERPs, generated by passive "oddball" paradigms. These neurophysiological and various clinical parameters were correlated with patient outcome using Pearson's coefficient. MAIN OUTCOME MEASURE: Three month Glasgow Outcome Scale (GOS). RESULTS AND CONCLUSION: Highly significant (P <0.001) correlations exist between long-latency ERP components and 3-month outcome. Short-latency EPs, brainstem (wave I-V) and somatosensory conduction times also correlate significantly with the GOS (P <0.01). Of the clinical measurements, pupillary response patterns, APACHE II and Glasgow Coma Scores (GCS) correlate significantly with outcome, as do the retrospective measures of duration of coma and post-traumatic amnesia (PTA) in survivors. Unfortunately, due to variance of long-latency responses, even in controls, absolute values cannot be relied upon as prognosticators. The presence of "mismatch negativity" predicted the return of consciousness (89.7% sensitivity and 100% specificity) and preceded changes in GCS. Its latency was the single best indicator of 90-day outcome from coma (r = -0.641).

Phosphorus metabolism during growth of lymphoma in mouse liver: a comparison of 31P magnetic resonance spectroscopy in vivo and in vitro.

Large phosphomonoester (PME) signals are detected in the phosphorus magnetic resonance spectra (31P MRS) of many neoplastic and rapidly dividing tissues. In addition, alterations in phosphodiester (PDE) signals are sometimes seen. The present study of a murine lymphoma growing in liver showed a positive correlation between the hepatic PME/PDE ratio measured in vivo by 31P MRS at 4.7 T and the degree of lymphomatous infiltration in the liver, quantified by histology. High-resolution 31P MRS of liver extracts at 9.7 T showed that the PME peak consists largely of phosphoethanolamine (PE) and to a lesser extent of phosphocholine (PC). The concentration of both PE and PC increased positively with lymphomatous infiltration of the liver. In vivo, the PDE peak contains signals from phospholipids (mostly phosphatidylethanolamine and phosphatidylcholine) and the phospholipid breakdown products glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC). Low levels of GPE and GPC were detected in the aqueous extracts of the control and infiltrated livers; their concentrations remained unchanged as the infiltration increased. The total concentration of phospholipids measured by 31P MRS of organic extracts decreased about 3-fold as the infiltration increased to 70%. Thus, our data showed that the increased PME/PDE ratio in vivo is due to both an increase in the PME metabolites and a decrease in the PDE metabolites. We propose that this ratio can be used as a non-invasive measure of the degree of lymphomatous infiltration in vivo.

Quantification of presynaptic alpha 2-adrenoceptors in rat brain after short-term DSP-4 lesioning.

The relative numbers of pre- and postsynaptic alpha 2-adrenoceptors were determined in various rat brain regions after short-term DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) lesioning. For these studies, rats pretreated with zimeldine (10 mg/kg i.p.) were injected with DSP-4 (100 mg/kg i.p.) and were killed either 3 or 15 days later. At the 3 day time-point, DSP-4 treatment produced marked reductions in the noradrenaline content of the cortex (93%), hippocampus (89%), hypothalamus (83%) and cerebellum (92%) with no change in the levels of dopamine or 5-HT. This treatment also decreased the number of alpha 2-adrenoceptors labelled with [3H]idazoxan in the cortex (20%), hippocampus (18%), cerebellum (24%) and hypothalamus (39%). Fifteen days after DSP-4 lesioning, the marked reductions of noradrenaline were sustained in the cortex, hippocampus and cerebellum, but there was a considerable reversal of the effect of DSP-4 in the hypothalamus. At this time-point, the decrease in alpha 2-adrenoceptors was attenuated in cortex (4%) and cerebellum (0%) and their number was increased in hippocampus (8%) and hypothalamus (7%). Together, the data argue that presynaptic alpha 2-adrenoceptors comprise approximately 20% of the total alpha 2-adrenoceptor population in the cortex, hippocampus and cerebellum, but about 40% of it in the hypothalamus. Furthermore, they also demonstrate that although the number of presynaptic alpha 2-adrenoceptors in rat brain can be determined by the reduction of radioligand-receptor binding shortly after DSP-4 lesioning, this effect is rapidly masked by receptor proliferation in response to noradrenergic denervation.

Monoarthritis induces complex changes in mu-, delta- and kappa-opioid binding sites in the superficial dorsal horn of the rat spinal cord.

Recently, an experimental model of monoarthritis was described in the rat induced by injection with Freund's adjuvant of the tibio-tarsal joint of one hindlimb. After injection, the clinical and behavioural signs of arthritis are stable from weeks 2 to 6 post-injection. Our purpose was to study the regulation of mu-, delta- and kappa-opioid binding sites in the superficial layers (laminae I-II) of the lumbar and cervical enlargements of the spinal cord 2, 4 and 6 weeks post-injection. Using quantitative receptor autoradiography and highly selective opioid ligands, we found complex changes consisting of a bilateral increase in specific [3H]DAMGO (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) and [3H]pCl-DPDPE (Tyr*-D-Pen-Gly-Cl-Phe-D-Pen) binding at 2 weeks post-injection and a bilateral decrease in [3H]U-69593 ((5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl]) specific binding at 4 weeks post-injection. These changes were restricted to the lumbar level. At 6 weeks post-injection, there was a bilateral increase in [3H]pCl-DPDPE specific binding at both lumbar and cervical levels. Altogether, these results suggest that, after probable local changes in endogenous opioid peptides, the three types of opioid binding sites are differentially involved in the development of the pathological process. These results contrast with the lack of significant modification in mu-, delta- and kappa-opioid binding classically reported at various levels of the spinal cord in polyarthritic rats at 3 weeks post-injection and verified for 2, 4 and 6 weeks post-injection in the present study.