Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Australian guidelines for the clinical care of people with COVID-19 - Australian National COVID-19 Clinical Evidence Taskforce

This guideline aims to provide specific, patient-focused recommendations on management and care of people with suspected or confirmed COVID-19. With the exception of chemoprophylaxis for the prevention of infection in people exposed to COVID-19, the guideline does not include other interventions used in the prevention of COVID-19 infection or transmission. Within each recommendation, the patient population of interest is specified.

Does Neospora caninum cause reproductive problems in pigs?

Neospora caninum is known to cause reproductive disturbances in several animal species, such as cattle, sheep, and goats. However, research on the effects of N. caninum on reproduction in pigs is limited. The objective of this study was to verify the transplacental transmission of N. caninum in pigs during several gestational stages. Twelve healthy Toxoplasma gondii and N. caninum seronegative female pigs were selected and separated into four groups of three animals each. Group A was maintained as a control group. Groups B, C, and D were inoculated intravenously with 2.9 × 107 tachyzoites of the N. caninum strain Nc1, 30 days before conception and at 45 and 90 days of gestation, respectively. Blood samples were collected from females periodically through IFAT for IgG and IgM screening to confirm the infection. At birth, after blood samples were collected from the piglets, they were then euthanized for the collection of the brain, heart, lung, liver, and diaphragm, which were then subjected to PCR. All inoculated gilts seroconverted (IgG) from the seventh day after inoculation. Nine of the 12 females expelled 24 mummified fetuses at the time of delivery, two in group A (eight), two in group B (four), three in group C (nine), and two in group D (three). Of the 24 mummified fetuses, nine were positive for N. caninum (one (25%) fetus of group B, seven (77.8%) of group C, and one (33.3%) of group D). A total of 126 live piglets were born. When the organs of the piglets from the inoculated females were analyzed by PCR for N. caninum, 88 (93.61%) were positive. All gilts inoculated produced at least one positive piglet. This demonstrates that there is transplacental transmission of N. caninum in all phases of gestation, regardless of the time of infection.

Using serum and plasma samples to assess failure of transfer of passive immunity in dairy calves.

The objectives of this study were (1) to determine the differences in IgG and total protein (TP) content of serum and plasma samples collected from the same calves; (2) to evaluate the correlation between calf serum and plasma IgG levels, Brix scores, and TP concentrations; (3) to determine whether different cut-off values should be used for plasma and serum to assess failure of transfer of passive immunity (FTPI) in dairy calves; and (4) to evaluate the level of agreement between results obtained from using serum and plasma samples of the same calves to assess FTPI using optimal cut-off values. Blood samples (n = 217) were collected from Holstein calves at 3 to 10 d of age on 30 commercial dairy farms in Nova Scotia and Newfoundland, Canada. Paired serum and plasma samples were analyzed for IgG concentration by the reference radial immunodiffusion assay, transmission infrared (TIR) spectroscopy, digital and optical Brix refractometers, and optical TP refractometer. The IgG concentrations measured by RID and TIR spectroscopy in serum were similar to those in plasma. However, the Brix and TP refractometer readings were significantly higher in plasma than in serum. The prevalence of FTPI in serum and plasma samples based on a RID-IgG concentration <10 g/L was 43.3 and 46.5%, respectively. The RID-IgG concentration was correlated with TIR-IgG (r = 0.92 and 0.89), digital Brix (r = 0.80 and 0.80), optical Brix (r = 0.77 and 0.77), and optical TP (r = 0.75 and 0.77) refractometers in serum and plasma, respectively. The correlations between paired serum and plasma IgG content were 0.85 by TIR spectroscopy, 0.80 by digital Brix, 0.77 by optical Brix, and 0.79 by optical TP refractometer. The optimal cut-off values for TIR spectroscopy, digital Brix, optical Brix, and TP refractometers to assess FTPI using serum were 13.1 g/L, 8.7% Brix, 8.4% Brix and 5.1 g/dL, respectively; and the optimal cut-off values with plasma were 13.4 g/L, 9.4% Brix, 9.3% Brix and 5.8 g/dL, respectively. When using these optimal cut-off values, the level of agreement (88.1%) between results derived from testing serum and plasma by TIR spectroscopy was substantial, with a kappa (κ) value of 0.76. The results derived from testing serum and plasma by digital Brix refractometer showed substantial agreement (83.4%), with a κ value of 0.65, which is higher than the agreement and κ value (74.7% and 0.51) reported for the optical Brix refractometer. Substantial agreement (81.6%) between serum and plasma TP was also obtained when using the optical TP refractometer, with a κ value of 0.63. In conclusion, serum or plasma samples can be used interchangeably for measuring IgG concentrations and assessing FTPI in dairy calves. However, different cut-offs must be used to assess FTPI depending on the sample matrix. Furthermore, results obtained from serum samples showed higher agreement with the reference RID assay than those obtained from plasma samples.

The effect of n-3 LCPUFA supplementation on oxidative stress and inflammation in the placenta and maternal plasma during pregnancy.

Pregnancy represents a state of heightened oxidative stress and inflammation, and these processes are further increased in pregnancy complications. The quality of the maternal diet is directly associated with maternal health and wellbeing, pregnancy and fetal outcomes, as well as the risk of pregnancy complications. Long chain polyunsaturated fatty acids (LCPUFAs) have significant potential to modify placental and fetal lipid environments and thereby modulate health outcomes. The omega-3 (n-3) LCPUFA in particular have been shown to exhibit both antioxidant and anti-inflammatory properties, and have potential therapeutic applications in reducing oxidative damage and inflammation during pregnancy. The purpose of this review is to provide an overview of our current understanding of the impact of maternal n-3 LCPUFA supplementation on oxidative stress and inflammation during pregnancy, with a particular focus on effects on the mother and the placenta.

Comparison of serum immunoglobulin G half-life in dairy calves fed colostrum, colostrum replacer or administered with intravenous bovine plasma.

In calves, passive immunity of immunoglobulins can be acquired through ingestion of colostrum or colostrum replacers. Plasma can been used to supplement immunoglobulins in healthy or sick calves. Serum half-life of colostral derived immuglobulin G (IgG) is estimated to be 20 days. Half-life of IgG is important in determining response to antigens and timing of vaccination in calves. To date studies evaluating half-life of colostrum replacer or plasma derived IgG are lacking. The objectives of this study were to compare the serum half-life of IgG derived from colostrum, colostrum replacer and plasma in dairy calves reared up to 35 days of age. Thirty Jersey calves were randomly assigned to receive colostrum or colostrum replacer by oroesophageal tubing or plasma by intravenous administration. Serum samples were collected at 2, 5, 7, 10, 14, 21, 28 and 35 days. Serum IgG concentrations were determined by radial immunodiffusion. The results indicated that half-life for IgG in colostrum fed (28.5 days) or plasma transfused calves (27.3 days) was longer than colostrum replacer fed calves (19.1 days). Further studies are required to evaluate pathogen specific immunoglobulins in order to recommend vaccination timing in calves fed colostrum replacers.

Entrapment in plasma microparticles: a promising strategy for antigen delivery.

We report the preparation of plasma microparticles (PMPs) from autologous blood plasma for sustained in vivo delivery of the entrapped antigens. The PMPs were prepared by high speed-stirring of calcium-enriched plasma, mixed with the antigen to be entrapped, in mineral oil. The preparation of PMPs did not necessitate addition of any external protein/enzyme nor special laboratory setup. Our results suggest that the PMPs release the entrapped invertase in a sustained manner both in vitro and in vivo, especially after crosslinking with glutaraldehyde. The preparations are reasonably stable to proteolysis and constitute strong candidates for eliciting immune response. Induction of humoral immune response by the PMP-entrapped invertase, as evident from the high antibody titers, was remarkable and comparable with that observed in animals receiving the antigen emulsified with Freund's Complete Adjuvant. Isotypic analysis of antibodies showed a Th1-biased immune response in animals administered uncrosslinked or crosslinked PMPs-entrapped invertase, especially after a booster dose. The analysis in animals of the group immunized with adjuvant-emulsified antigen suggested a combined Th1 and Th2 response. PMP-entrapment also caused high expression of surface markers (CD80 and CD86) on antigen presenting cells, as well as effector T-cells surface markers (CD4(+) and CD8(+) ) as revealed by FACS. The study suggests that PMPs offer remarkable promise as adjuvant-free and biocompatible vaccine delivery systems.

Effect of feeding maternal colostrum or plasma-derived or colostrum-derived colostrum replacer on passive transfer of immunity, health, and performance of preweaning heifer calves.

The objective of this study was to evaluate the effect of feeding maternal colostrum (MC), a plasma-derived (PDCR) or colostrum-derived colostrum replacer (CDCR) on passive transfer of immunity, health, and performance of preweaning heifer calves. Preplanned contrasts were performed for MC versus CR (PDCR combined with CDCR) and PDCR versus CDCR. At birth, calves were randomly assigned to 1 of 3 treatment groups: MC (n=49), 3.8L of maternal colostrum; PDCR (n=49), 550 g (1 dose; 150 g of IgG) of a PDCR; or CDCR (n=49), 470 g (1 dose; 100g IgG) of a CDCR. The best total protein cutoff for determining passive transfer was >5.2, 5.6, and 5.1g/dL for MC, PDCR, and CDCR, respectively. Serum total protein was greater for calves fed MC (mean ± SE; 6.14 ± 0.11 g/dL) than for calves fed PDCR (5.29 ± 0.11 g/dL) and CDCR (5.27 ± 0.11 g/dL). Serum IgG concentrations were greater for calves fed MC (2,098 ± 108 g/dL) than for calves fed PDCR (927 ± 107 g/dL) or CDCR (1,139 ± 108 g/dL). Apparent efficiency of absorption was greater for CDCR than PDCR (38.8 ± 3.0 vs. 21.6 ± 3.0%). Adequate passive transfer was greatest for MC (91.8%), followed by CDCR (49%) and PDCR (28.6%). Calves fed MC had greater weaning weights and body weight gain than calves fed CR. Morbidity was lower for calves fed MC (46.9%) than for calves fed PDCR (71.4%) or CDCR (67.3%). Calves fed MC tended to have lower mortality than calves fed CR. Given the conditions of this trial, feeding 3.8L of MC was superior to feeding one dose of CR. Further research is needed to evaluate calf performance when a higher dose of CR is fed.

[Microvascular effects of burn plasma transfer and therapeutic options in a rat model]. / Mikrovaskuläre Effekte des Verbrennungsplasma-transfers und therapeutische Optionen im Tiermodell.

INTRODUCTION: Thermal injuries with more than 20% of burned body surface area (BSA) lead to systemic shock with generalised oedema in addition to local tissue destruction. This condition, known as burn injury, is caused by immunmodulative mediators whose individual significance is not known in detail. We present an experimental model where plasma of burned animals (burn plasma) is transmitted to healthy animals, to trigger burn iniury without performing direct burn trauma. MATERIAL AND METHODS: The systemic oedema is measured by extravasation of fluorescent albumin in mesenterial venules of Wistar rats. In addition, leukocyte-endothelial interactions ("leukocyte rolling and sticking") is examined. RESULTS: The systemic capillary leak is induced by both direct thermal trauma as well as by infusion of burn plasma. This is evident even after plasma dilution (1% in Ringer's lactate) of the burn plasma. In addition, topical therapy for burned animals (donors) with cerium nitrate led to a significant reduction of plasma extravasation in receiver animals. In addition, systemic antioxidant therapy with high-dose vitamin C of receiver animals, led to a significant reduction of the capillary leak. Leukocyte-endothelial interactions are not significantly affected in either case. CONCLUSION: In summary, for the first time a reliable model of burn injury has been established, which eliminates mediator-independent effects. In addition, our studies show that antioxidant therapy with high doses of vitamin C and topical treatment with cerium nitrate both reduce the systemic capillary leak in receiver animals. Their positive influence could therefore soon be integrated in clinical treatment algorithms.

Proteínas séricas de potros da raça Puro Sangue Árabe recém-desmamados ou com mais de trinta dias de desmame / Serum protein profile in Arabian foals recently weaned or at more than thirty days after weaning

A fase perinatal do desenvolvimento constitui um dos períodos de vida mais desafiadores para o sistema imunológico dos potros. O objetivo do presente estudo foi verificar o perfil protéico sérico de parâmetros relacionados à imunidade de equinos jovens no período perinatal, verificando-se a transferência de imunidade passiva. Oito animais desmamados há um dia, formaram o Grupo 1 (G1), enquanto vinte animais desmamados há mais de trinta dias formaram o Grupo 2 (G2). A concentração sérica de proteína total foi determinada por refratometria. Para o fracionamento das proteínas, utilizou-se eletroforese em gel de acrilamida. Os resultados obtidos foram submetidos à análise de medidas repetidas e ao teste Tukey (p<0,05) para comparação das médias. As concentrações de IgA apresentaram diferença (p<0,05) entre os grupos, porém os valores observados encontravam-se dentro do considerado normal para equinos adultos. Não houve diferença (p>0,05) nas concentrações de IgG. O estabelecimento adequado da imunidade celular ocorre durante a fase neonatal, nos animais que ingerem adequadamente o colostro e o leite. O presente estudo determinou diferenças no perfil protéico sérico de parâmetros relacionados à imunidade de equinos jovens no período imediato ao desmame, comparados com animais desmamados há mais de 30 dias. De acordo com os valores observados, concluiu-se que os animais, mesmo desmamados precocemente, obtiveram transferência adequada de imunidade passiva.

The perinatal phase of foal development is one of the most challenger period for the immune system. The present study has analyzed serum protein profile, considering variables related to immunity in foals at the perinatal phase, verifying passive immunity transfer. The group 1 (G1) contained eight foals evaluated one day after weaning, and group 2 (G2) included twenty foals at more than thirty days after weaning. Total protein concentration was determined by means of refractometry. The concentration of serum proteins was determined through sodium dodecyl sulphatepolyacrylamide gel electrophoresis. Results were submitted to analysis of variance and Tukey test (P<0.05). IgA concentration showed difference (P<0.05) between the two studied groups, however data were within adult healthy horses normal values. IgG didn't show statistical difference (P>0.05). The cellular immunity establishment occurs in the neonatal phase, in foals that suckled colostrum and milk properly. The present study showed differences in serum protein profile, considering variables related to immunity, in foals immediately after weaning comparing to foals at more than 30 days after weaning. According to the observed values, we conclude that foals, even early weaned, showed proper passive immunity tranfer.

Post-transfusion mortality among recipients of ABO-compatible but non-identical plasma.

BACKGROUND AND OBJECTIVES: The consequences of ABO-compatible non-identical plasma for patient outcome have not been studied in randomized clinical trials or large cohort studies and use varies widely in the absence of evidence-based policies. We investigated if transfusion with compatible instead of identical plasma confers any short-term survival disadvantage on the recipients. MATERIALS AND METHODS: The cohort of all 86 082 Swedish patients who received their first plasma transfusion between 1990 and 2002 was followed for 14 days and the risk of death in patients exposed to compatible non-identical plasma compared to recipients of only identical plasma. RESULTS: After adjustment for potential confounding factors, there was an increased mortality associated with exposure to ABO-compatible non-identical plasma, with the excess risk mostly confined to those receiving 5 or more units (relative risk, 1.15; 95% confidence interval, 1.02-1.29). Stratification by blood group indicated higher risks in group O recipients, especially when the compatible plasma was from a group AB donor. CONCLUSIONS: This study suggests that ABO-compatible non-identical plasma is less safe than identical plasma. Subanalyses by blood group suggest a role for circulating immune complexes. Our findings may have policy implications for improving transfusion safety.

[Effect of scalp-acupuncture on plasma and cerebral TNF-alpha and IL-1beta contents in acute cerebral ischemia/reperfusion injury rats].

OBJECTIVE: To explore the underlying mechanism of scalp-acupuncture therapy in the treatment of acute cerebral ischemia (ACI) in the rat. METHODS: A total of 140 SD female rats were randomly assigned to sham-operation (n=20), model (n=60), scalp-acupuncture (SA, n=60) groups, and the later two groups were further divided into 24 h, 48 h and 72 h subgroups separately, with 20 cases in each. Among them, 70 rats were used for cerebral tissue section, and the other 70 cases for homogenating cerebral tissue. ACI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h and reperfusion. EA (2/100 Hz, 2 mA) was applied to bilateral "Dingnie Houxiexian" (MS 7) and "Dingnie Qianxiexian" (MS 6) for 20 min, once daily for 1 d, 2 d and 3 d respectively. The rat's neurological severity score (NSS) was assessed before and after EA. Blood and brain tissue were sampled for detecting TNF-alpha and IL-1beta contents respectively with enzyme-linked immunosorbent assay. Haematoxylin-eosine (H&E) staining method was used for displaying the inflammatory cells in the ischemic brain tissue. RESULTS: (1) After ACI, NSS at each time-point increased significantly, while compared with model group, NSS of SA group decreased apparently 72 h after ACI (P<0.01). Compared with the corresponding time-points of sham-operation group, the number of inflammatory cells, plasma and cerebral TNF-alpha and IL-1beta contents at 24 h, 48 h and 72 h in model group increased considerably (P<0.01, 0.05). In comparison with the corresponding time-points of model group, the number of inflammatory cells at 48 h and 72 h, plasma and cerebral TNF-alpha and IL-1beta contents at 72 h in SA group declined significantly (P<0.01). CONCLUSION: Scalp-acupuncture can relieve inflammatory cell infiltration, and reduce plasma and cerebral TNF-alpha and IL-1beta contents in ACI rats, which may contribute to its effect in promoting neurofunctional recovery.

Effects of perioperative recombinant human IFN-gamma (rHuIFN-gamma) application in vivo on T cell response.

In spite of the well-known immunoregulatory effects of recombinant human interferon-gamma (rHuIFN-gamma), in vitro clinical trials in trauma patients remain inconclusive. In vitro studies have shown that IFN-gamma has an effect on lymphocyte responses in addition to immunomodulatory effects on the monocyte/macrophage system. To investigate the in vivo effect of rHuIFN-gamma perioperatively on lymphocyte behavior in surgical patients, we studied 46 anergic patients undergoing major surgery. Treated patients (T, n = 24) received 100 microg rHuIFN-gamma subcutaneously (s.c.), and control patients (C, n = 22) received a placebo on preoperative days -7, -5, and -3 in a controlled, double-blinded placebo trial. Whole blood cultures were stimulated with mitogen on perioperative days, and cytokines were investigated in the supernatants. Interleukin-2 receptor (IL-2R) levels were significantly elevated in the treatment arm during the postoperative period (p < 0.05). The postoperative enhancement of IL-4 in C was completely attenuated in T (p < 0.05). IL-2 levels were elevated perioperatively in T but not in C. No significant effect of rHuIFN-gamma could be demonstrated on IL-10 or lymphocyte proliferation in vitro. From this pilot study, we conclude that preoperative in vivo immunomodulation of lymphocyte function with rHuIFN-gamma in anergic patients is effective. It improves immunoreactivity, as shown by elevated IL-2R levels. Elevated IL-2 and suppressed IL-4 levels indicate a shift toward a Th1-driven lymphocyte response.

Desloratadine reduces allergen challenge-induced mucinous secretion and plasma exudation in allergic rhinitis.

BACKGROUND: Rhinorrhea is a key symptom of allergic rhinitis and this disease feature is reduced by antihistamine treatment. The nasal output of fluid in allergic rhinitis is associated with luminal appearance of bioactive molecules emanating from the microcirculation as well as the secretory apparatus. OBJECTIVE: In the present study, we examined the effects of antihistamine treatment on nasal symptoms and output of mucinous secretions and plasma. METHODS: Desloratadine (5 mg) was administered orally once daily for 5 days in a placebo-controlled, crossover design to 24 patients with allergic rhinitis. Nasal challenges with diluent and allergen (100 to 10,000 SQ-U) were carried out on day 5 of the treatment. The nasal mucosa was lavaged with saline, and symptoms were scored 10 minutes after each allergen challenge and 1 to 4 hours after the challenge series. Nasal lavage fluid levels of fucose and alpha2-macroglobulin were determined as indices of mucinous secretion and plasma exudation, respectively. RESULTS: The allergen challenges produced nasal symptoms, including rhinorrhea, and increased nasal output of fucose and alpha2-macroglobulin. Desloratadine reduced the nasal symptoms (P < 0.05 to 0.001) and output of fucose (P < 0.05 at 100 and 1,000 SQ-U) and alpha2-macroglobulin (P < 0.05 at 1,000 SQ-U). In both treatment groups, symptoms and nasal lavage fluid levels of fucose and alpha2-macroglobulin returned toward prechallenge levels 1 to 4 hours after the allergen challenge series. CONCLUSION: We conclude that the antihistamine desloratadine, in addition to a symptom-reducing effect, also reduces acute allergen challenge-induced mucinous secretion and plasma exudation in allergic rhinitis.

Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism.

Efficient alveolar epithelial repair is crucial for the restoration of the injured alveolar epithelial barrier in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). We hypothesized that pulmonary edema fluid from patients with ALI /ARDS would inhibit alveolar epithelial repair as measured in an in vitro epithelial wound-repair model using the human alveolar epithelial-like cell line A549. In contrast to our initial hypothesis, pulmonary edema fluid from patients with ALI/ARDS increased alveolar epithelial repair by 33 +/- 3% compared with pooled plasma from healthy donors (p < 0.01). By contrast, the plasma and the pulmonary edema fluid from patients with hydrostatic pulmonary edema, and the plasma from patients with ALI/ARDS had similar effects on epithelial repair as pooled plasma from healthy donors. Inhibition of interleukin-1beta (IL-1beta) activity by IL-1 receptor antagonist reduced alveolar epithelial repair induced by ALI/ARDS edema fluid by 46 +/- 4% (p < 0.001), indicating that IL-1beta contributed significantly to the increased epithelial repair. In summary, pulmonary edema fluid collected early in the course of ALI/ARDS increased alveolar epithelial repair in vitro by an IL-1beta-dependent mechanism. These data demonstrate a novel role for IL-1beta in patients with ALI/ARDS, indicating that IL-1beta may promote repair of the injured alveolar epithelium.

[A delayed hemolytic transfusion reaction due to irregular antibodies with an anti-Kidd(a) specificity]. / Verzögerte hämolytische Transfusionsreaktion durch irreguläre Antikörper der Spezifität Anti-Kidd(a).

HISTORY AND CLINICAL FINDINGS: A 56-year-old woman was admitted for replacement of a previously implanted right hip prosthesis which had become loose (no infection). She limped painfully on a shortened leg whose mobility was markedly impaired. At the site of the previous operation the pelvis was lower by about 2 cm; the scar looked well healed. INVESTIGATIONS: Routine laboratory tests were normal except for moderately raised erythrocyte sedimentation rate (18/ 27 mm). There was complete loosening of the prosthesis on X-ray. TREATMENT AND COURSE: Intraoperative bleeding from a branch of the inferior gluteal artery required blood transfusion and further erythrocyte infusions became necessary. Jaundice developed on the 4th postoperative day and 7 days later the direct Coombs test was positive with demonstrable agglutination. Free irregular erythrocytic anti-Kidd(a) (anti-jk[a]) antibodies were found in the serum. To counteract the delayed haemolytic transfusion reaction, exclusively jk(a)-negative erythrocytes were infused. The jaundice gradually disappeared and the bilirubin values became normal. CONCLUSION: Jaundice and signs of haemolysis after erythrocyte transfusion may be due to delayed transfusion reaction and should be investigated with the direct Coombs test.

Cytolysis of hemocytes induced by serum and plasma in three crustaceans, Panulirus japonicus, Penaeus japonicus, and Homarus americanus.

The effects of serum and/or plasma of three crustacean species on cellular morphology of homologous and heterologous hemocytes were observed using an in vitro short-term culture system. When hemocytes of the spiny lobster, Panulirus japonicus, isolated from hemolymph were mixed with serum of the same species, rapid cytolysis occurred in hyaline and semigranular cells. Plasma of Panulirus japonicus dialyzed against artificial sea water (dialyzed plasma) had the same cytolytic effect on hyaline and semigranular cells. Although the granular cells are not lysed, exposure to serum and plasma does produce changes in morphology and behavior (adhesion and spreading). Dialyzed plasma of the shrimp (Penaeus japonicus) and the lobster (Homarus americanus) also showed the same phenomena on homologous hemocytes. Dialyzed plasma of these three species had a less pronounced cytolytic effect on heterologous hemocytes. The cytolytic activity of the dialyzed plasma was weakened by heat treatment and inactivated by protease treatment. These results suggest that a protein factor(s) that specifically induces bursting of hyaline and semigranular cells exists in plasma of crustaceans.