Effects of routine treatment with nonsteroidal anti-inflammatory drugs at calving and when lame on the future probability of lameness and culling in dairy cows: A randomized controlled trial.

Claw horn lesions (CHL) are reported as the most common cause of lameness in intensive dairy systems. Despite their prevalence, the underlying pathological mechanisms and preventive strategies for CHL remain poorly understood. Recent advances have pointed to the role of inflammation in disease aetiopathogenesis. Moderating inflammation from first calving may lead to long-term benefits and a viable intervention for treating and preventing disease. We conducted a 34-mo randomized controlled trial to investigate the effects of routine treatment with the nonsteroidal anti-inflammatory drug ketoprofen at calving and during treatment for lameness, on the future probability of lameness and culling, caused by exposure to normal farm conditions. A cohort of dairy heifers were recruited from a single, commercial dairy herd between January 8, 2018, and June 22, 2020, and randomly allocated to one of 4 treatment groups before first calving. The lactating herd was lameness scored every 2 wk on a 0 to 3 scale, to identify animals that became lame (single score ≥2a) and hence required treatment. Animals in group 1 received a therapeutic trim and a hoof block on the sound claw (if deemed necessary) every time they were treated for lameness. Animals in group 2 received the same treatment as group 1 with the addition of a 3-d course of ketoprofen (single dose daily) every time they were treated for lameness. Animals in group 3 received the same treatment as group 2 with the addition of a 3-d course of ketoprofen (single dose daily) starting 24 to 36 h after each calving. Animals in group 4 received a 3-d course of ketoprofen (single dose daily) every time they were identified with lameness. No therapeutic trim was administered to this group, unless they were identified as severely lame (a single score ≥3a). Animals were followed for the duration of the study (ending October 23, 2020). Probability of lameness was assessed by a lameness outcome score collected every 14 d. Data on culling was extracted from farm records. One hundred thirty-two animals were recruited to each group, with data from 438 animals included in the final analysis (111 in group 1, 117 in group 2, 100 in group 3, and 110 in group 4). Mixed effect logistic regression models were used to evaluate the effect of treatment group on the ongoing probability of lameness. Compared with the control group (group 1), animals in group 3 were less likely to become lame (odds ratio: 0.66) and severely lame (odds ratio: 0.28). A Cox proportional hazards survival model was used to investigate the effect of treatment group on time to culling. Compared with group 1, animals in groups 2 and 3 were at reduced risk of culling (hazard ratios: 0.55 and 0.56, respectively). The lameness effect size we identified was large and indicated that treating a cohort of animals with the group 3 protocol, would lead to an absolute reduction in population lameness prevalence of approximately 10% and severe lameness prevalence of 3%, compared with animals treated in accordance with conventional best practice (group 1).

Effects of mannan-oligosaccharide and Bacillus subtilis supplementation to preweaning Holstein dairy heifers on body weight gain, diarrhea, and shedding of fecal pathogens.

The objective of this clinical trial was to evaluate the effectiveness of probiotic, prebiotic, and synbiotic supplementation on average daily weight gain (ADG), duration of diarrhea, age at incidence of diarrhea, fecal shedding of Cryptosporidium oocysts, enteric pathogens, and the odds of pneumonia in preweaning dairy heifer calves on a commercial dairy. Feeding prebiotics and probiotics may improve health and production of calves. Hence, healthy Holstein heifer calves (n = 1,801) from a large California dairy were enrolled at 4 to 12 h of age and remained in this study until weaning at 60 d of age. Calves were block randomized to 1 of 4 treatments: (1) control, (2) yeast culture enriched with mannan-oligosaccharide (prebiotic), (3) Bacillus subtilis (probiotic), and (4) combination of both products (synbiotic), which were fed in milk twice daily from enrollment until weaning. Serum total protein at enrollment and body weight at 7, 42, and 56 d of age were measured. Fecal consistency was assessed daily for the entire preweaning period. A subgroup of 200 calves had fecal samples collected at 7, 14, 21, and 42 d for microbial culture and enumeration of Cryptosporidium oocysts by direct fluorescent antibody staining. Synbiotic-treated calves had 19 g increased ADG compared with control calves for overall ADG, from 7 to 56 d. From 42 to 56 d, prebiotic-treated calves had 85 g greater ADG and synbiotic-treated calves had 78 g greater ADG than control calves. There was no difference in duration of the first diarrhea episode, hazard of diarrhea, or odds of pneumonia per calf with treatment. Probiotic-treated calves had 100 times lower fecal shedding of Cryptosporidium oocysts at 14 d and prebiotic-treated calves had fewer Escherichia coli and pathogenic E. coli at 42 d compared with control calves. Although there were no effects on duration of diarrhea or pneumonia incidence, greater ADG in the late preweaning period may reflect treatment effects on enteric pathogens during the rearing process. The decreased shedding of Cryptosporidium should reduce infectious pressure, environmental contamination, and public health risks from Cryptosporidium. Our findings suggest ADG and potential health benefits for calves fed prebiotics, probiotics, and synbiotics and can help the dairy industry make informed decisions on the use of these products in dairy production.

Field survey to evaluate space allowances for dairy cows in Great Britain.

Housing conditions can affect health of cows by increasing exposure to biological, chemical, and physical hazards, resulting in increased disease. A report in 2014 indicated that 99% of UK dairy cows are housed during winter months and that an increasing number of farms are committing to year-round indoor-housing management systems. Current literature does not provide a clear understanding of the relationship between cow health, welfare, and production, and the housing environment. Loafing space, in this case defined as non-feed, non-lying, and non-high traffic areas of the housed environment, is considered an important component of housing for dairy cows; however, the scientific literature associated with this subject is sparse internationally. The aim of this research was to explore current housing of dairy cows across Great Britain, with specific focus on understanding the practices and variability associated with space allowance. A secondary aim was to explore farmer opinions and knowledge on the value of living space. A single researcher visited 53 randomly selected farms, from a representative sample group, once during the winter housing period 2017-18. Data collection consisted of 3 elements: collation of basic farm details, precise measurement of adult dairy cow accommodation, and a questionnaire to capture farmer opinions on space allowances. Statistical analysis was undertaken to assess variation among farms in total space, loafing space, and living space per cow. A new metric, termed "living space," was defined to describe the additional space availability for dairy cows above that deemed to be a baseline requirement. Large variability was identified between farms in total space available per cow, with a range from 5.4 to 12.7 m2 [mean = 8.3 m2, median = 8.2 m2, interquartile range (IQR) = 1.9 m2]. The mean living space was 2.5 m2, with a range of 0.5 m2 to 6.4 m2 (median = 2.4 m2, IQR = 1.6 to 3.2 m2). Responses from a farmer questionnaire on importance of loafing space revealed that farmers felt it was essential for cow welfare, over half of farmers scoring this ≥8 on a 0 to 10 scale. Farmers were categorized into 4 latent classes based on their attitudes toward the importance of loafing space. In a linear model to predict the "living space" provided on each farm, geographical location and latent class of farmer attitude were covariates significantly associated with the amount of space provided. This study is the first worldwide to quantify variability in loafing and living spaces for dairy herds; further research is required to evaluate the extent to which variation in quantity and quality of space influences cow health, welfare, and productivity, as well as farm economics and emissions.

Less is more: creation and validation of a novel, affordable suturing simulator for anorectal surgery.

BACKGROUND: Duty hour restrictions have increased the role of simulation in surgical education. A simulation that recreates the unique visual, anatomic, and ergonomic challenges of anorectal surgery has yet to be described. The aim of this study was to develop a low-cost, low-fidelity anorectal surgery simulator and provide validity evidence for the model. METHODS: A novel, low-fidelity simulator was constructed, and anorectal surgery workshops were implemented for general surgery interns at a single institution. Face and content validity were assessed with separate questionnaires using a 5-point Likert scale. Participants performed a simulated hemorrhoid excision with longitudinal wound closure, and transverse wound closure. Time-to-task completion and quality of suturing/knot tying were evaluated by a blinded observer to assess construct validity. RESULTS: Material cost was US $11 per simulator. We recruited 20 first-year surgery residents (novices) and 4 practicing colorectal surgeons (experts), and conducted 3 workshops in 2014-2016. All face and content validity measures achieved a median score greater than 4 (range 4.0-5.0). Time-to-task completion was significantly lower in the expert cohort (hemorrhoid excision with longitudinal wound closure: 195 vs. 477 s and transverse closure: 79 vs. 192 s, p < 0.001 for both). Suturing and knot-tying scores were significantly higher in the expert cohort for both tasks (p < 0.05 for all comparisons). CONCLUSIONS: Our low-fidelity, low-cost anorectal surgery model demonstrated evidence of face, content, and construct validity. We believe that this simulator could be a useful instrument in the education of junior surgical trainees and will allow residents to obtain proficiency in anorectal suturing tasks in conjunction with traditional surgical training.

Experience of laparoscopic incisional hernia repair in kidney and/or pancreas transplant recipients.

Despite the wide popularity of laparoscopic incisional hernia repair (LIHR) in the nontransplant population, there are very few reports of LIHR available in abdominal organ transplant patients and none exclusively on kidney and/or pancreas (KP) transplant patients. We retrospectively reviewed a consecutive series of LIHR in KP transplant recipients performed over a period of 4 years and compared the results with LIHR in non-transplant patients during the same period. A total of 36 transplant patients were compared with 62 nontransplant patients. There were five patients converted to the open procedure in the transplant and four in nontransplant patients (p-NS). There were three seromas and one patient had a bowel perforation in the transplant group versus eight seromas, one bowel perforation and one small bowel obstruction noted in the nontransplant group. One patient in each group had a mesh infection requiring explant. Patients were followed up for a mean period of 2.2 years in the transplant group and 3 years in the nontransplant group. Overall there were five recurrences in the transplant group and four in the nontransplant group (p = NS). These results suggest that that LIHR is a safe and effective alternative to open repair.

Relationship of mixed lymphocyte culture response to HL-A histocompatibility antigens. Effect of allele plus one antigen match.

The influence of varying degrees of incompatibility for HL-A antigens on one-way mixed lymphocyte cultures (MLC) has been investigated. Reactions have been compared to a simple expression of HL-A antigens, allele compatibility, and a proposal considering the potential influence of antigen matching in relationship to allele compatibility. As expected, HL-A compatibility was associated with nonstimulated cultures, but significant correlation was not observed when incompatibility was expressed in terms of HL-A antigen or allele mismatching. When the relationship of both was considered, however, a second distinctive group was demonstrated that shared one allele plus one antigen of the second allele. Within this group no stimulation, even with augmented culture conditions, was observed in some families. Employing these same criteria, there was no significant difference in the MLC response in those groups that were incompatible for both alleles regardless of the number of matched antigens or the group that shared an allele but differed by both antigens of the second allele. These results support the concept of an intimate relationship between the loci coding for HL-A antigens and mixed culture reactions. They suggest that HL-A haplotype incompatibility acting as a unit is the primary stimulus of the MLC response, and that the immunogenicity of the haplotype also relates to whether or not one antigen is common to the stimulating and responding cell.

BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF.

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.

Amifostine prior to lethal irradiation prevents allogeneic bone marrow engraftment in mice.

We and others have demonstrated that the milieu created by ionizing radiation (IR) used for conditioning plays a major role in the development of acute graft-versus-host disease (aGVHD). We reasoned that antioxidants that could inhibit IR induction of inflammatory cytokines and/or apoptosis might reduce the incidence or severity of aGVHD. Therefore, BALB/c mice were treated with amifostine, n-acetyl cysteine (NAC) or pyrrolidine dithiocarbamate (PDTC) prior to transplantation with allogeneic C57Bl/6 bone marrow and spleen cells. None of 30 amifostine-pretreated mice developed weight loss or other signs of aGVHD and they rejected their allogeneic transplants. However, pretreatment to groups of five mice each with molar equivalent doses of NAC or PDTC accelerated death, and lower doses did not prevent aGVHD. In vitro tests demonstrated that PDTC and NAC acted as pro-oxidants when incubated with isolated normal mouse lymphocytes, whereas amifostine and its active metabolite WR-1065 did not. The conclusion that amifostine protected immune function from IR in vivo was further supported by the fact that amifostine and WR-1065 preserved the response of radiated normal lymphocytes to respond to PHA and both stimulated growth of non-radiated, non-PHA-treated normal lymphocytes in vitro. Taken together, these data caution the use of amifostine in allogeneic transplantation.

Heterogeneity of antibody response to human platelet transfusion.

To study the antibody response to human platelet transfusions, nine thrombocytopenia patients with bone marrow failure were given 6 U (3X10(11)) of random platelet concentrates twice a week. Before transfusion, none of the patients had preexisting antibodies detectable with lymphocytotoxicity, platelet aggregation, or capillary leukoagglutination techniques. After receiving 18-78 U of platelets, they became refractory to further transfusions of random platelets and alloantibodies were detectable. Two patterns of antibody response could be identified. In three patients, the sera were not lymphocytotoxic with a panel of standard cells in which all the known HLA antigens in the first and second series were represented at least once. Yet, they caused platelet aggregation with 30, 24, and 60%, respectively, of a donor population studied. The aggregating activities were inhibited by antihuman IgG but not by antihuman IgA or antihuman IgM antiserum. The aggregating antibodies could be absorbed out with donor platelets but not lymphocytes or granulocytes. Antibodies from two of these patients aggregated platelets of their respective siblings matched for both HLA haplotypes. Transfusion of platelets from these two siblings did not increase the platelet count while platelets obtained from aggregation-negative donors did. The sera from the remaining six patients were lymphocytotoxic with 15-100% of the panel of standard cells. They also had aggregating antibodies, which could be absorbed out by both platelets and lymphocytes, suggesting that they were HLA antibodies. These data suggest that the development of platelet-specific antibodies may play an important role in the immunological rejection of isologous platelets, and should be considered in the selection of donors for patients who are refractory to platelets from random donors.

New granulocyte antigens demonstrated by microgranulocytotoxicity assay.

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.

Specific repression of the yeast silent mating locus HMR by an adjacent telomere.

The yeast silent mating loci HML and HMR are located at opposite ends of chromosome III adjacent to the telomeres. Mutations in the N terminus of histone H4 have been previously found to derepress the yeast silent mating locus HML to a much greater extent than HMR. Although differences in the a and alpha mating-type regulatory genes and in the cis-acting silencer elements do not appear to strongly influence the level of derepression at HMR, we have found that the differential between the two silent cassettes is largely due to the position of the HMR cassette relative to the telomere on chromosome III. While HML is derepressed to roughly the same extent by mutations in histone H4 regardless of its chromosomal location, HMR is affected to different extends depending upon its chromosomal positioning. We have found that HMR is more severely derepressed by histone H4 mutations when positioned far from the telomere (cdc14 locus on chromosome VI) but is only minimally affected by the same mutations when integrated immediately adjacent to another telomere (ADH4 locus on chromosome VII). These data indicate that the degree of silencing at HMR is regulated in part by its neighboring telomere over a distance of at least 23 kb and that this form of regulation is unique for HMR and not present at HML. These data also indicate that histone H4 plays an important role in regulating the silenced state at both HML and HMR.

Comparison of conventional laparoscopic and hand-assisted oncologic segmental colonic resection.

BACKGROUND: Laparoscopically assisted colon resection has evolved to be a viable option for the treatment of colorectal cancer. This study evaluates the efficacy of hand-assisted laparoscopic surgery (HALS) as compared with totally laparoscopic surgery (LAP) for segmental oncologic colon resection with regard to lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay in an attempt to help delineate the role of each in the treatment of colorectal cancer. METHODS: Patient charts were retrospectively reviewed to acquire data for this evaluation. Between June 2001 and July 2005, 40 patients underwent elective oncologic segmental colon resection (22 HALS and 18 LAP). The main outcome measures included lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay. RESULTS: The two groups were comparable in terms of demographics. The tumor margins were clear in all the patients. The HALS resection resulted in a significantly higher lymph node yield than the LAP resection (HALS: 16 nodes; range, 5-35 nodes vs LAP: 8 nodes; range, 5-22 nodes; p < 0.05) and significantly shorter operative times (HALS: 120 min; range, 78-181 min vs LAP: 156 min; range, 74-300 min; p < 0.05). Both groups were comparable with regard to length of hospital stay, pedicle length, and intraoperative blood loss. However, the LAP group yielded a significantly smaller incision for specimen extraction (LAP: 7 cm; range, 6-8 cm vs HALS: 5.5 cm; range, 5-7 cm; p < 0.05). CONCLUSION: The findings suggest that hand-assisted laparoscopic oncologic segmental colonic resection is associated with shorter operative times, more lymph nodes harvested, and equivalent hospital stays, pedicle lengths, and intraoperative blood losses as compared with the totally laparoscopic approach. The totally laparoscopic technique was completed with a smaller incision. However, this less than 1 cm reduction in incision length has doubtful clinical significance.

Predicting outcome of procedures to slow intestinal transit.

Procedures designed to slow intestinal transit in patients with the short-bowel syndrome (SBS) have unpredictable outcomes. Our aim was to evaluate the outcome and predictive factors for this complication in SBS patients. Ten patients (37-61 years) underwent reversed segment (n = 9) or nipple valve creation (n = 1). All patients had remnant lengths over 90 cm and rapid intestinal transit times. All subjects had benign diseases, including Crohn's (n = 3). Six patients had a colon remnant. SBS had been present for 8 to 150 months. Nine (90%) required parental nutrition (PN) preoperatively. A procedure was performed either alone (n = 5) or concurrently with an ostomy closure (n = 3), an ostomy revision (n = 1), or a fundoplication (n = 1). There was one postoperative complication (urinary tract infection) and no deaths. Two patients developed bacterial overgrowth. One required repair of an ileocolonic stricture. One reversed segment was taken down 12 months later. Five (50%) patients improved (off PN), five remained on PN or had persistent diarrhea. Patients with a successful outcome were more likely to have had ostomy takedown (60% vs 0%). The duration of SBS; presence of Crohn's disease, a colon remnant, or type 1 anatomy; and the transit times were similar in both groups. Adjusted remnant length (small intestine +30 cm for type 2 anatomy and +60 cm for type 3) was similar (136 +/- 20 vs 154 +/- 25 cm). Procedures may benefit half of selected SBS patients with adequate remnant length and rapid transit. Successful patients are more likely to have an ostomy takedown, but the outcome is less determined by transit time or intestinal length if over 90 cm.

Immunological and ultrastructural characterization of true histiocytic lymphoma in the northern pike, Esox lucius L.

An epidemic of a malignant neoplasm occurs in northern pike, Esox lucius L., from the Aland Islands of Finland. The neoplasm is morphologically similar to other pike hemic tumors reported in other areas of the world. Pike normal tissues showed evolutionary conservation with the mammalian intermediate filament proteins cytokeratin, desmin, vimentin, neurofilament protein, and glial fibrillary acidic protein; tumor cells are positive for vimentin, suggesting that the neoplasm is of mesenchymal origin. Hemic tissue mononuclear cells undergo polyclonal stimulation by the known mammalian T- and B-lymphocyte mitogens phytohemagglutinin P, concanavalin A, tuberculin-purified protein derivative, and lipopolysaccharide W; pike tumor cells are nonreactive. Pike normal hemic tissue mononuclear cells are variously positive for surface and cytoplasmic immunoglobulins, using rabbit anti-pike immunoglobulin M and cross-reactive mouse anti-carp immunoglobulin M antibodies; tumor cells, however, are not positive. The tumor cells were also diffusely stained with sodium fluoride-sensitive nonspecific esterase. The foregoing suggest that the neoplasm is not of B-lymphocytic or plasmacytic derivation, while the T-lymphocytic as opposed to monocytic derivation cannot be excluded on the basis of marker studies. The ultrastructural studies, however, suggest a neoplasm of histiomonocytic derivation, while the absence of sinusoidal infiltration of tumor cells to head kidney, spleen, liver, or peripheral blood suggests that it is a piscine analogue of human true histiocytic lymphoma. Population dynamics studies indicate that the neoplasm affects primarily sexually mature males 5 to 6 yr of age, but does not at present appear to be a major factor affecting Aland pike populations.

Reduced expression of the cyclin-dependent kinase inhibitor gene p57KIP2 in Wilms' tumor.

We have previously shown that the p57KIP2 gene, which encodes a cyclin-dependent kinase inhibitor, undergoes genomic imprinting and lies within a 700-kb domain of imprinted genes on 11p15, including IGF2 and H19. Loss of heterozygosity and loss of imprinting (LOI) of this region are frequently observed in Wilms' tumor (WT) and other embryonal malignancies. Although LOI of p57KIP2 was observed in some WTs (approximately 10%), allele-specific expression was preserved in most tumors examined. Because our initial studies were inconclusive concerning the absolute expression level of p57KIP2 in WT, we developed a sensitive and quantitative RNase protection assay to determine if changes in p57KIP2 expression play a role in WT. Expression of p57KIP2 was found to be virtually absent in 21 of 21 WTs compared to matched normal kidney from the same patients, as well as compared to fetal kidney. We also examined p57KIP2 expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19. Although p57KIP2 was undetectable in BWS tongue, similar results were also observed in postnatal non-BWS tongue samples. Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57KIP2. However, one BWS patient did show LOI of p57KIP2 in skin fibroblasts. Thus, p57KIP2 is part of a domain of genes on 11p15 that show altered expression and, in some cases, altered imprinting in WT and BWS.

Lack of imprinting of three human cyclin-dependent kinase inhibitor genes.

Genomic imprinting is an epigenetic modification in the germline leading to parental allele-specific gene expression in somatic cells. We have previously found that imprinted genes can be abnormally expressed or silenced in tumors and that the cyclin-dependent kinase inhibitor (CKI) CDKN1C (p57KIP2) is normally imprinted, with preferential expression of the maternal allele. Here we analyze the imprinting status of three additional CKIs, the abnormal expression and/or chromosomal localization of which has been implicated in human malignancy: CDKN1A, CDKN1B, and CDKN2C. Allele-specific expression was examined by reverse transcription-PCR, using primers that span transcribed polymorphisms as well as exon/intron boundaries, to distinguish cDNA products from genomic DNA. Biallelic expression was observed for all three genes in both fetal and adult tissues. Thus, genomic imprinting is not a generalized feature of CKIs.

Reversed Intestinal Segment Revisited.

BACKGROUND: Reversed segments (RS) designed to slow intestinal transit and improve absorption in patients with short bowel syndrome (SBS) are performed infrequently, and patient selection remains controversial. Our aim was to evaluate patient selection and outcome for RS in SBS patients. METHODS: Sixteen adult patients underwent RS among 520 SBS patients. All patients had remnant length >80 cm and rapid intestinal transit. Ten patients had a colon remnant and 12 had an ostomy. SBS was present for 8 to 150 months prior to RS. RESULTS: RS was performed either alone (n = 9) or concurrently with ostomy closure (n = 5) or creation (n = 2). There were 3 postoperative complications and no deaths. Three patients had bacterial overgrowth. One required repair of an ileocolonic stricture. Two reversed segments were taken down 12 months and 96 months later. Two patients subsequently underwent serial transverse enteroplasty (STEP) procedures, and 1 had isolated intestinal transplant. Fourteen (88%) required parenteral nutrition (PN) pre-operatively and 2 (12%) had intractable diarrhea. Nine (56%) patients improved and 7 (44%) remained on PN or had persistent intractable diarrhea. Patients with a successful outcome were similar to those without improvement with respect to ostomy takedown, duration of SBS, Crohn's disease, intestinal length, a colon remnant, anatomy, and transit time. CONCLUSIONS: Reversed segments significantly benefit one half of selected SBS patients who have rapid transit but adequate remnant length. Outcome in individual patients remains difficult to predict. Subsequent operation is frequently required. This procedure is applicable to a small proportion of SBS patients.

HLA antigens and schizophrenia.

We typed 45 schizophrenic patients for 35 HLA antigens and compared their frequencies with 1,263 population controls. No significant differences between schizophrenics and controls were found. When the schizophrenics were subtyped, a significant (P less than .05) excess of Aw26 was found among the hebephrenics, compared with the population controls. When the published literature on schizophrenia-HLA associations was surveyed, none of the reported associations were found to be consistent across studies. Some possible explanations for the heterogeneity among studies are discussed and it is concluded that an association between schizophrenia and any of the HLA antigens has not yet been demonstrated.

Hyperammonemic encephalopathy in urinary diversion with urea-splitting urinary tract infection.

We present two cases of hyperammonemic encephalopathy secondary to urea-splitting urinary tract infection with urinary diversion. One patient had a ureterosigmoidostomy, the other an ileal loop diversion. Neither patient had significant underlying liver disease, but both had considerable muscle atrophy that may have predisposed them to develop hyperammonemia. Medical therapy did not provide long-term control of symptoms. In both cases, hyperammonemic encephalopathy resolved after revision of their urinary diversions. The probable mechanism of the metabolic derangements produced by urea-splitting urinary tract infections is reviewed. We suggest that patients with urinary diversion who develop hyperammonemic encephalopathy secondary to a urea-splitting urinary tract infection be treated with surgical revision of the urinary system to improve drainage and decrease bowel contact time.