Does the manic/mixed episode distinction in bipolar disorder patients run true over time?

OBJECTIVE: The authors sought to determine whether the manic/mixed episode distinction in patients with bipolar disorder runs true over time. METHOD: Over an 11-year period, the observed distribution of manic and mixed episodes (N=1,224) for patients with three or more entries in the management information system of a community mental health center (N=241) was compared to the expected distribution determined by averaging 1,000 randomly generated simulations. RESULTS: Episodes were consistent (all manic or all mixed) in significantly more patients than would be expected by chance. CONCLUSIONS: These data suggest a pattern of diagnostic stability over time for manic and mixed episodes in patients with bipolar disorder. Careful prospective studies of this issue are needed.

The value of prophylactic antibiotics in aorat-coronary bypass operations: a double-blind randomized trial.

Prospective and retrospective studies were performed to determine the efficacy of prophylactic antibiotics in preventing infections in patients undergoing arota-coronary bypass. One-hundred five patients were randomized in a double-blind fashion to receive either methicillin or saline-placebo for 3 days. The over-all infection rate was 26.7% with 48.9% in the control group and 8.6% in the methicillin group (p less than 0.001). Significant sternal wound infection developed in 21.3% of the control group and 0% of the methicillin group (p less than 0.01). Staphylococcus aureus was the predominant organism causing significant sternal infection (methicillin group versus control group, 5.2% and 21.3%; p less than 0.05). The length of postoperative stay in hospital and the number of days with fever was significantly greater in the control group than in the methicillin group (p less than 0.001). During the same period of time, 160 patients were studied retrospectively. Of these, 150 patients received cephalothin prophylaxis and 10 received methicillin. Comparison of the rates of infection in the cephalothin group to the total methicillin group (prospective and retrospective) showed no significant difference. The study clearly demonstrated that a short course of prophylactic antistaphlococcal penicillin or cephalosporin is justified in aorta-coronary bypass.

Open-heart surgery in Jehovah's Witnesses: experience in a Canadian hospital.

Jehovah's Witnesses have religious belief precluding the use of blood. Few centers have attempted open-heart surgery bound by such strictures; as a result, availability of therapy for such patients has been limited. Many groups that have extensive experience with hemodilution for cardiopulmonary bypass have noted that these procedures can often be done with little or no use of blood. Our experience with 21 adult patients is presented in this paper.

Is mastectomy overtreatment for Paget's disease of the nipple?

The standard local management for Paget's disease of the nipple is currently mastectomy although this may well represent overtreatment. The place of breast conserving surgery is somewhat uncertain. We have reviewed the casenotes of 146 patients with Paget's disease of the nipple, and compared the mortality and recurrence rates between 74 women who had undergone mastectomy and 31 women who had breast conserving surgery. There was no significant difference in either local or overall treatment failure rates between these two treatment groups. We conclude that breast conserving treatment maybe an appropriate alternative to mastectomy for the management of Paget's disease, where clear margins of excision can be achieved. However, a randomized prospective study is needed to confirm this.

Effects of divalproex versus lithium on length of hospital stay among patients with bipolar disorder.

The medical records of all inpatients with bipolar disorder at the Connecticut Mental Health Center in 1997 were examined to compare length of stay for patients who began monotherapy with divalproex (27 treatment starts) and lithium (20 treatment starts). No statistically significant difference was found in length of stay (11. 5+/-6.9 and 10.3+/-5.2 days for patients on divalproex and lithium, respectively) or other length-of-stay variables. Demographic variables, diagnostic variables, and dosages of neuroleptics and benzodiazepines used adjunctively were similar as well. Dosages and blood levels for divalproex and lithium were consistent with practice guidelines. Prospective randomized studies are needed to compare the cost-effectiveness of divalproex and of lithium in the treatment of bipolar disorder.

Luteolysis in mares after endometrial biopsy.

The length of diestrus was not changed in 4 mares by taking endometrial biopsy specimens during estrus. In contrast, taking endometrial biopsy specimens on postovulation day 4 induced premature luteolysis and significantly (P less than 0.05) reduced the length of diestrus. A concurrent decrease in serum progesterone occurred to verify the premature luteolysis in these mares. Bacterial cultures of endometrial swab samples from these mares were negative for growth at the first estrus before and after the last biopsy procedures, indicating that luteolysis was induced by the biopsy procedure and was not due to uterine infection. Seemingly, infusion of antibiotic solution after endometrial biopsy on postovulation day 4 prevented premature luteolysis.

Oxacillin, cephalothin, and vancomycin tube macrodilution MBC result reproducibility and equivalence to MIC results for methicillin-susceptible and reputedly tolerant Staphylococcus aureus isolates.

Measurement of antimicrobial killing endpoints of Staphylococcus aureus isolates in tube macrodilution MBC testing has been difficult because of multiple technical factors. A total of 41 fresh clinical isolates and 23 reputedly oxacillin-tolerant strains were examined by a modification of the Taylor MBC method. Oxacillin, cephalothin, and vancomycin MBCs were equal to MICs for most strains and were seldom more than fourfold greater than the corresponding MICs after a 48-h incubation. Oxacillin MBC result reproducibility for S. aureus ATCC 25923 and clinical isolates was better than that of cephalothin and vancomycin, and reproducibility improved after a 48-h incubation. Measurement of the percentage of the initial inoculum remaining after 24 and 48 h of incubation for the strains for which the MBCs were highest confirmed improved killing over a wide range of antimicrobial concentrations after a 48-h incubation. Since S. aureus MBC testing is expensive, is subject to error, and almost always gives results equal to the MIC, we suggest that MBC testing is an experimental reference laboratory test that should not be done by clinical microbiology laboratories. Antimicrobial selection should be based on reproducible and standardized MIC tests.

Cost of treatment failure for major depression: direct costs of continued treatment.

Understanding subsequent costs of treating patients who fail initial treatment for depression is critical in cost-effectiveness analysis. This prospective observational study calculated such costs in a community mental health center. Total mean annual direct per-patient costs were $6,818 to $8,661. This total was markedly higher than those reported in studies that were based partially on the assumptions of expert panels rather than observed utilization rates. These results suggest that in settings similar to the present study, antidepressant treatments with higher failure rates may carry a marked hidden cost disadvantage.

Lack of expression of alpha or omega interferons by the horse conceptus.

Horse conceptuses were collected on Days 13, 15, 20 and 25 after ovulation. Whole conceptuses (Days 13 and 15) or extra-embryonic membranes (Days 20 and 25) were homogenized and poly-adenylated RNA (poly A RNA) was isolated by binding to oligo (dT)-cellulose. Poly A RNA (1 microgram/well) was separated by size on a denaturing 1% agarose gel and blotted onto nitrocellulose filters (northern blotting). DNA probes were prepared from plasmids containing equine alpha 1, omega 1 and omega 2 interferons and human beta actin. The presence of messenger RNA (mRNA) was detected by specific hybridization of 32P-cDNA probes labelled by random priming. After hybridization at 37 degrees C, filters were washed at room temperature and 56 degrees C, and bands of 32P-cDNA:mRNA heteroduplexes were identified by autoradiography on Kodak XAR-5 radiographic film. The presence of bands on autoradiographs of Southern blots of horse DNA indicated that hybridization and probe conditions were adequate to support hybridization. The actin probe hybridized to all mRNA tested on northern blots, indicating that the mRNA was of high aquality. No hybridization was seen on northern blots using any of the interferon probes. These results indicate that poly A RNA with a high degree of homology to alpha or omega interferons does not accumulate in the horse conceptus.

Changes in equine endometrial retinol-binding protein RNA during the estrous cycle and early pregnancy and with exogenous steroids.

A cDNA library was constructed from poly(A) RNA obtained from Day 14 nonbred equine endometrium. A cDNA probe for porcine retinol-binding protein (RBP) was used to screen the library, and a complete cDNA sequence (1133 bp, excluding the poly(A) tail) was obtained. Endometrial biopsies were obtained from cycling, nonbred mares at Days 0, 1, 4, 8, 10, 11, 13, and 15 and from pregnant mares at Days 11, 13, 15, and 17 after ovulation (n = 2 mares each day). Endometrial biopsies were also taken from 18 noncycling anestrous mares after the following treatments: C (vehicle control for 1 day, n = 3), E (estradiol-17 valerate, 5 mg/day for 6 days, n = 3), P (progesterone, 250 mg/day for 6 days, n = 4), ESP (E for 6 days followed by, P for 6 days, n = 4), and ELP (E for 6 days followed by P for 12 days, n = 4). Northern blot analyses were performed on total RNA (30 micrograms) using cDNA probes to equine (e) RBP and human glyceraldehyde-3 phosphate dehydrogenase (G3PDH). The RBP RNA levels (normalized to G3PDH) from nonbred mares were low during early diestrus and increased after Day 10, and RBP RNA levels from pregnant mares were similar to those of nonbred mares for corresponding days. E tended to decrease endometrial RBP RNA; and P, ESP, and ELP increased it compared to C. There were no significant differences among P, ESP, and ELP RBP RNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and initial characterization of calcyclin and phospholipase A2 in equine conceptuses.

For development to proceed normally, the appropriate genes must be expressed in the correct tissues and in the correct time frame. Knowledge of gene expression during development provides information about the changes taking place within the conceptus as well as possible reasons for pregnancy failure. However, little is known about gene expression during development in the equine conceptus. In this study, we examined differences in gene expression between day 12 and day 15 equine conceptuses by suppression subtractive hybridization. This technique was used to isolate transcripts that are more abundantly expressed in day 15 conceptuses compared to day 12 conceptuses. Between day 12 and 15 of pregnancy in horses, maternal recognition of pregnancy occurs, gastrulation is taking place, and mesoderm is beginning to form. Fifty cDNA clones were isolated, sequenced, and compared to known sequences in the GenBank database. Two cDNA clones identified that were of primary interest were calcyclin and phospholipase A2. Calcyclin is a calcium-binding protein of the S-100 protein family that has been found in mouse decidua and trophoblast. Calcyclin was found to be expressed in both day 12 and 15 equine conceptuses, with approximately a 30-fold increase in transcript abundance between days 12 and 15. Phospholipase A2 is an enzyme that cleaves phospholipids to release fatty acids and is involved in arachidonic acid release needed for prostaglandin, thromboxane, and leukotriene synthesis. Multiple forms of PLA2, that appear to be differentially regulated in day 12 and 15 conceptuses, were detected by northern blotting.

Differential gene expression in day 12 and day 15 equine conceptuses.

Complex changes in gene expression must occur at the proper time and in the appropriate tissues for pregnancy to be successful. Therefore, research aimed at defining the regulation of gene expression in conceptuses is of critical importance. However, information on developmentally regulated changes in gene expression in horse conceptuses is sparse and inadequate. In the present study, suppression subtractive hybridization was used to identify genes that are expressed more highly at day 15 than on day 12 of gestation. This period encompasses maternal recognition of pregnancy and the beginning of mesoderm formation and gastrulation. Clones (n=50) were isolated, partially sequenced and the sequences obtained were compared with known sequences to determine their identity. Analysis of glyceraldehyde-3-phosphate dehydrogenase and alpha-fetoprotein (AFP) in subtracted and unsubtracted samples indicated a high efficiency of subtraction. Some of the genes identified included pregnancy-associated glycoprotein (PAG), fumarylacetoacetase, cytokeratins 8 and 18, and isocitrate and succinate dehydrogenases. Differential gene expression of PAG and AFP between days 12 and 15 was confirmed. PAG expression increased approximately 30 times and AFP expression increased at least 1000 times between days 12 and 15.

Eosinophil- and eosinophil granule-mediated pneumocyte injury.

The function of the eosinophil in eosinophilic pulmonary syndromes and asthma is uncertain. To determine if eosinophils might play a harmful role in these conditions, we cocultured purified human eosinophils, eosinophil major basic protein (MBP), and chromatographically eluted eosinophil granule fractions with human A549 and rat type II pneumocytes. Damage to these target cells was measured as cell lysis and nonlethal cell detachment. We found that unstimulated intact eosinophils affected minimal lysis or detachment of either pneumocyte target, but eosinophils stimulated with phorbol myristate acetate and other activators produced time- and dose-dependent nonlytic detachment of both targets. In contrast, supernatants from activated eosinophils did not produce significant injury, suggesting that close apposition of the effector and target cells was required. Catalase and superoxide dismutase did not inhibit the detaching activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not responsible for mediating this form of injury. In contrast to our findings with intact eosinophils, we observed that the addition of purified eosinophil MBP to pneumocytes caused marked cytolysis with little detachment. When sequential fractions of eosinophil granules separated by Sephadex G-50 chromatography were added to A549 and rat type II pneumocyte targets, it was found that different fractions produced distinct forms of injury. Higher molecular weight fractions containing lysosomal enzymes and eosinophil peroxidase produced predominantly detachment, whereas fractions enriched in MBP produced lysis. These results indicate that intact eosinophils can produce nonlytic detachment of alveolar pneumocytes that is probably not dependent on the generation of toxic oxygen radicals but rather appears to be mediated by granule-associated products, possibly lysosomal enzymes. Furthermore, although intact eosinophils are not capable of lysing alveolar epithelial cells under the conditions of our assay, MBP has the potential to do so when the protein is released in high enough concentrations. The in vivo relevance of these findings in eosinophilic lung diseases may be that eosinophils, by producing both desquamation and death of alveolar epithelium cells, may increase the permeability of the alveolus to fluid and cells. Moreover, these forms of damage might also enhance the ingress of inhaled antigens across the pulmonary epithelial barrier, thus increasing immunologic sensitization.

Comparative modelling and analysis of amino acid substitutions suggests that the family of pregnancy-associated glycoproteins includes both active and inactive aspartic proteinases.

The pregnancy-associated glycoproteins (PAGs) are secretory products synthesized by the outer epithelial cell layer (chorion) of the placentas of various ungulate species. The amino acid sequences of eight PAGs have been inferred from cloned cDNA of cattle and sheep, as well as of the non-ruminant pig and horse. We compare the PAG sequences and present results of the three-dimensional models of boPAG-1 and ovPAG-1 that were constructed on the basis of the crystal structures of homologous porcine pepsin and bovine chymosin using a rule-based comparative modelling approach. Further, we compare peptide binding subsites defined by interactions with pepstatin and a decapeptide inhibitor (CH-66) modelled on the basis of crystal structures of other aspartic proteinases. We have extended our analysis of the peptide binding subsites to the other PAG molecules of known sequence by aligning the PAG sequences to the structural template derived from the pepsin family and by making use of the three-dimensional models of the boPAG-1 and ovPAG-1. The residues that are likely to affect peptide binding in the boPAG-1, ovPAG-1 and other PAG molecules have been identified. Sequence comparisons reveal that all PAG molecules may have evolved from a pepsin-like progenitor molecule with the equine PAG most closely related to the pepsins. The presence of substitutions at the S1 and other subsites relative to pepsin make it unlikely that either bovine, ovine or the porcine PAG-1 have catalytic activity. Only two of the eight PAGs examined (porcine PAG-2 and equine PAG-1) retain features of active aspartic proteinases with pepsin-like activity. Our results indicate that in the PAGs so far characterized the peptide binding specificities differ significantly from each other and from pepsin, despite their high sequence identities. Analysis of the various peptide binding subsites demonstrates why both bovine and ovine PAG-1 are capable of binding pepstatin. The strong negative charge in the binding cleft of boPAG-1 and ovPAG-1 indicates a preference for lysine- or arginine-rich peptides. PAGs represent a family where the possible peptide binding function may be retained through their binding specificities, but where the catalytic activity may be lost in some cases, such as the boPAG-1, ovPAG-1 and the poPAG-1.

Early pregnancy loss in brood mares.

During 1985, linear-array ultrasonography was used to study early pregnancy loss in commercial brood mares: 600/1115 (54%) of the cycles resulted in detected pregnancy at Week 2 after ovulation and 80 (13%) of these pregnancies resulted in early pregnancy loss. The pregnancy loss rate was significantly higher (P less than 0.05) for twin pregnancies (10/41) than for singleton pregnancies (70/559). The pregnancy loss rate was significantly higher (P less than 0.05) at 2-4 weeks (29/60) than at 6-8 weeks (12/60). The pregnancy rate was significantly less (P less than 0.05) for post-partum mares inseminated at the foal heat (157/302) than for those inseminated at a subsequent oestrus (203/334). Mares with a history of endometritis had a significantly higher (P less than 0.05) per cycle pregnancy loss rate (7/26) than did mares with a history of not having endometritis (64/498). When mares that had lost pregnancies were re-mated, 37/75 (49%) detectable pregnancies resulted and 7 (19%) of these pregnancies were again lost. The per cycle pregnancy rate was 56% (153/273), 55% (177/319), 60% (130/216), 51% (72/142), 45% (34/76) and 33% (12/36) for mares aged 2-5, 6-9, 10-13, 14-17, 18-21 and greater than 21 years, respectively. The corresponding per cycle pregnancy loss rates were 12%, 14%, 9%, 14%, 24% and 33%.