The presence of B-cell nodules does not necessarily portend a less favorable outcome to therapy in patients with acute cellular rejection of a renal allograft.

The presence of B-cell nodules in kidney biopsies of patients undergoing acute renal allograft rejection has been reported to be associated with glucocorticoid resistance and a high risk of graft failure. In an attempt to corroborate this observation, biopsies of renal transplants that evidenced Banff grade I A acute rejection were examined for the presence of B- or T-cell nodules, the detection of which was correlated with the therapeutic response. Biopsies from 14 consecutive renal transplant recipients with a diagnosis of acute cellular rejection were examined for the presence of T (CD3-positive) or B (CD20-positive) cells by immunohistochemistry. All patients were biopsied because of a rise in serum creatinine. No biopsy showed evidence of acute humoral rejection. Immunofluorescence microscopy was negative for C4d deposition in peritubular capillaries. There were no neutrophils in the peritubular or glomerular capillaries. Five patients had T-cell nodules; four had B-cell nodules; three had both T- and B-cell nodules; two had no nodules. All biopsies contained CD3-positive cells in the tubules and in the interstitium. In all but one of the patients, episodes of acute rejection were treated with steroids (one received thymoglobulin). Furthermore two patients received mycophenolate mofetil and one, sirolimus. There were no significant differences among the groups in either the initial creatinine or the creatinine after therapy. The presence of B-cell nodules in renal allograft biopsies of patients experiencing acute cellular rejection did not portend a less favorable outcome.

Effect of cyclosporine and delayed graft function on posttransplantation erythropoiesis.

The effect of delayed graft function and immunosuppressive drugs on posttransplant erythropoiesis was studied prospectively in 18 living-related (LR) and 84 cadaver-donor (CD) recipients. Eight of 18 LR and 20 of 84 CD recipients received antilymphoblast globulin (ALG) in addition to azathioprine and prednisone. Sixty-four CD recipients received cyclosporine (CsA) with prednisone. In the absence of rejection reticulocytosis began 6.7 +/- 0.2 days following graft implantation in azathioprine-only-treated LR recipients. This was lengthened by ALG to 9.4 +/- 0.3 and 9.9 +/- 0.7 days in LR and CD recipients, respectively, whose grafts functioned immediately. Delayed graft function prolonged onset of reticulocytosis to 15.9 +/- 0.9 days in ALG-treated but not in CsA-treated recipients (5.8 +/- 0.4 days). The shortest latency was noted in CsA-treated recipients (4.9 +/- 0.5 days) with immediately functioning grafts. The earlier onset of reticulocytosis of CsA-treated recipients was followed by statistically significant blunting of peak reticulocytosis, which correlated with a slower rate of correction of anemia (delta Hct = 0.19/day) compared with non-CsA-treated recipients (delta Hct = 0.34/day). Early rejection was associated with abrogation of reticulocytosis and correction of anemia without regard to immunosuppressive regimen) until rejection was reversed. Erythropoietin (EPO) was measured sequentially in 5 patients with immediate function. In 4 of 5 cases changes in EPO preceded those in reticulocytosis. EPO rose from a mean of 13 mU/ml pretransplant to a peak of 50 within 3 weeks and decreased to 18 mU/ml within 6 weeks of graft implantation. At six months posttransplant, normalized reticulocyte counts were only 55% higher (1.75 vs. 1.13%) but hematocrit had increased from 26 +/- 1% to 42 +/- 1%. Hematocrit varied inversely with serum creatinine, which was highest in CsA-treated patients with initial delayed graft function. We conclude that correction of anemia posttransplantation is driven by EPO but other factors may also be important, that neither ATN nor ALG-therapy have clinically important effects on erythropoiesis, and that CsA reduced "effective" erythropoiesis and influences correction of anemia--particularly if delayed graft function complicates the initial course posttransplantation.

A comparison of the effects of cyclosporine versus antilymphocyte globulin on delayed graft function in cadaver renal transplant recipients.

There has been concern that cyclosporine's nephrotoxicity increases the incidence of delayed graft function (DGF), prolongs periods of oliguria, and reduces graft survival. In order to further study whether CsA should be used in DGF, we conducted a randomized prospective trial of the effect of CsA versus antilymphocyte globulin on the effects of DGF. Between 12/22/85 and 3/11/88, all patients with DGF after an initial 12-24 hr of CsA were randomized to either daily Minnesota ALG and prednisone or lower-dose CsA (10 mg/kg/day) and prednisone. Resolution of DGF was defined as a lack of dialysis dependency and a 25% fall in the serum creatinine (CR). If DGF was not resolved by 2 weeks, transplant renal biopsies were performed to assess the presence of occult rejection. CsA (10 mg/kg/day) was initiated in the ALG group only after resolution of the DGF. Of the 45 patients who recovered graft function, 19 received ALG and 26 received CsA. CsA significantly prolonged the duration of DGF (ALG 9.74 days, CsA 13.69 days, P = 0.035) but did not result in a prolongation of hospitalization. No difference in CR was found between the two groups at 1 month, 3 months, 6 months, or 12 months. Mean CR at 12 months was 1.98 mg/dl for ALG versus 1.96 mg/dl for CsA. Overall graft survival did not differ in the CsA and ALG groups (P = 0.33). CsA does slightly increase the duration of DGF as compared with ALG but has no effect on one-year serum CR or one-year graft survival. Since there appeared to be no harmful long-term effects of the slight lengthening of DGF, a lower-dose of CsA protocol with biopsy surveillance for occult rejection can be used in patients with DGF.

Surgery in the patient with acute or chronic renal failure.

Medical management of the surgical patient with renal dysfunction revolves primarily around the application of sound medical principles used in the care of all patients. In this article, the unique peculiarities associated with renal failure are stressed. Knowledge of these points is vital in securing a favorable outcome for the patient.

Analysis of fertility indices of cows with extended postpartum anestrus and other reproductive disorders compared to normal cows.

An analysis of computerized data on the incidence and consequences of reproductive disorders was performed on 84,818 lactations in more than 100 high producing Kibbutz dairy herds during six semiannual recording periods. The average incidence of primary reproductive disorders, which included retained placenta, abnormal lochia, endometritis, postpartum anestrus, cystic ovaries, negative pregnancy examinations and repeat breeders, was 50.4%. During all recording periods we were able to observe recurrence and repeatability of these reproductive disorders and of the fertility indices consequently seen. Cows with uterine infections diagnosed and treated before Day 20 post partum had better fertility indices than those diagnosed and treated later. The conception rate to first inseminations and the overall conception rate to all inseminations of cows with postpartum anestrus was significantly lower, while the percentage of "problem cows" (not pregnant by Day 150 post partum) was significantly higher, than in normal cows. The incidence of cystic ovaries in cows with a previous diagnosis of reproductive disorders was 2 to 3 times higher when compared to cows without such a diagnosis.

Analysis of fertility indices of cows with reproductive disorders and of normal cows in herds with low and normal fertility.

Semiannual computer printouts of reproductive disorders diagnosed in high producing Israeli dairy herds were evaluated for a comparison of fertility indices of diseased and normal cows in low (LFH) and normal fertility herds (NFH). In 16,910 cows, conception rates to first AI in cows with reproductive disorder were >50% below those in normal cows (P<0.001). For both groups of cows, conception rates were lower in LFH (P<0.0001). A comparison of fertility indices between LFH (5, 171 cows) and NFH (14,573 cows) revealed, in addition a higher overall conception rate and a lower percentage of cows still open on Day 150 post partum (problem cows, (P<0.0001), as well as a higher pregnancy rate for NFH (P<0.001), for cows with reproductive disorder and for normal cows in these herds. In herds with predominantly uterine-related reproductive disorder, a high incidence of postpartum anestrus was seen infrequently; while in herds with a high incidence of postpartum anestrus, postbreeding anestrus was equally high (P<0.05 - 0.001). In general reproductive disorder have been shown to have long-term negative effects on fertility indices in both LFH and NFH, but with more serious consequences in LFH. Since a sizeable percentage of normal cows can be identified, reproducing normally under identical management conditions, cows in both kinds of herds with reproductive disorder must be less resistant to environmental stress. Thus, while cows with reproductive disorders maintained their general health and their high level of productivity, they responded either immediately with uterine disturbances or they refused to cycle properly, and they conceived later. A case can be made that all reproductive disorders represent disease entities influenced by management factors.

Observations on some environmental factors connected with fertility in heat stressed cows.

A field study was performed using 15 Kibutz dairy herds, in which 4195 cows situated in northern Israel were milked to determine the influence of climatological factors and nutritional regimes on the conception rate during the summer period (July-September). The Overall Conception Rate (OCR) during summer was 28.2% (17.3-41.9%) compared to 40% in the spring (May-June). The conception rate from first inseminations (CRl) was 31.3% during summer and 45.3% during spring. The OCR of the nullipara heifers in the same herds was 59.2% in summer and 60.4% in spring. The OCR in summer was negatively correlated with the minimum temperature (r=-0.53), the relative humidity at 0800 hrs. (r=-0.47), and the relative humidity at 1400 hrs (r=-0.49), whereas the CRl during summer was negatively correlated only with the minimum temperature (r=-0.51). In 12 (13) feeding groups of cows examined in 6 herds, no correlation was found between rectal temperatures and the actual milk productions of the cows. In 14 (15) herds, the milk production in summer was lower than in spring; the decrease varied from 0.9%-18.2% (average 7.8%). A highly significant negative correlation was found between the OCR and the various parameters of protein intake: grams of crude protein/cow/day, grams of crude protein/kg FCM/day, and percentage of protein from total dry matter. Particularly high correlations were found between the OCR and the average amounts of protein/kg FCM/day in milk of all cows (r=-0.84).

Epidemiological study on factors influencing fertility indices in Israeli dairy herds.

The objective of this study was to determine feeding factors connected with differences in the fertility of Israeli Kibbutz dairy herds. In an epidemiological case-control survey, data from 30, low-fertility Kibbutz dairy herds having a mean overall conception rate of 35% in multiparous cows were compared with the data from 30, high-fertility Kibbutz dairy herds having a mean overall conception rate of 48% in multiparous cows. Nutritional factors accounted for 67% of the differences between low-fertility and high-fertility herds in the overall conception rate of multiparous cows, while only 4.8% could be related to the body condition during the dry period. Among the factors which occurred more frequently in the low-fertility than in the high-fertility herds were 1) a higher average protein density and lower energy/protein ratio was fed during lactation and 2) a single feeding group was maintained for all lactating cows. 3) There were phytoestrogens in the silage or alfalfa hay, fed during lactation. 4) Faulty dry period was instituted, which was defined as the presence of at least one of the following three practices: a) the daily feed was above 3 kg of high lactation mix; b) more than 15 Mcal of net energy per day was given during the first part of the dry period; c) more than 30% of the cows were obese during the dry period. Three or more risk factors were found in one high-fertility herd and in 20 low-fertility herds. This finding emphasizes the importance of identifying and removing risk factors as a possible means for improving the reproductive performance of herds.

Genetic analysis of reproductive disorders in Israeli Holstein dairy cows.

The heritability of common reproductive disorders was asessed in Israeli Holstein cows. Data were collected from 76,000 calvings on 102 collective farms (kibbuts) over a 36-mo period. The disorders considered were those of retained placenta, abnormal lochia, endometritis, anestrus, ovarian cysts with anestrus and ovarian cysts with nymphomania. The statistical model included fixed effects of herd-year, month of calving, duration of previous pregnancy, interaction between calving difficulty and sex of offspring, and the random effect of the sire. Herd-year effects consituted 0.68 of the explained variance of the incidence of retained placenta and approximately 0.89 of all the other disorders. Sire and calving-month effects were significant (P<0.05) for all the disorders. Heritability estimates of the disorders were 0.01 for retained placenta, abnormal lochia, and endometritis; 0.02 for anestrus; and 0.03 for all disorders. Correlations between any two disorders did not exceed 0.20. High genetic correlations were found between retained placenta and either abnormal lochia (0.90) or endometritis (0.70), while moderate genetic correlations were found among each of these and anestrus (0.30). Reproductive disorders occur as part of a complex which may be efficiently controlled by management measures. Nevertheless, breeding for resistance to reproductive disorders may also be feasible by using appropriate sires evaluated on a large number of daughters.

[Effect of the composition of the ration during the dry period on fertility and milk production of Holstein cows in Israel]. / Einfluss der Zusammensetzung der Ration in der Trockenzeit auf die Fruchtbarkeit und Milchleistung von Israeli-Holstein-Kühen.

In each for of kibbutzin herds located in Israel the dry cows were divided in two feeding groups. The experimental group, in totally 266 cows, obtained only oat, barley or wheat hay ad libitum, whereas the control group (n = 253) was fed additionally mix or silage up to four kg dry matter. The cows in the control group responded in the following lactation with a 1.3 kg higher average FCM per day (p = 0.02) and with a 1.7 kg higher maximum FCM (p = 0.01) in comparison to the experimental group. The differences between the experimental and control group in A. I.-parameters days open, conception rate on first insemination and percent problem cows were rather small. However, the frequency of retained placenta and ovary cysts was significantly (p less than 0.05) higher in the control group than in the experimental group. In one herd the influence of body condition between the end of lactation, dry period and 50-80 days p.p. as well as the change of body weight between the end of lactation and calving on milk production and fertility could be evaluated. A decrease of one body condition score unit between the dry period and 50-80 days p.p. was associated with an increase of FCM by 2.01 kg (p less than 0.01), a decrease of the conception rate by 21% (p less than 0.05) and an elongation of the days open by 23.6 days (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)