High versus "low" dose corticosteroids in recipients of cadaveric kidneys: prospective controlled trial.

Corticosteroids have the major role in the immunosuppressive treatment of patients who have received renal transplants. Despite their extensive use there is still debate about the appropriate dose that will prevent rejection of the renal allograft with the least morbidity. From March 1979 to November 1981 a randomised controlled trial of high (33 patients) v low oral dose (34 patients) of prednisolone along with azathioprine was conducted in recipients of first cadaveric transplants who had received a blood transfusion within six months of transplantation. The main difference in outcome between the two groups was a high incidence of some infections in the high dose group. Patient mortality, graft survival, transplant function, and number of rejection episodes were indistinguishable in the two groups, but rejection episodes tended to occur later in the high dose group. These findings suggest that the use of lower doses of corticosteroids soon after cadaveric renal transplantation does not jeopardise graft survival and results in lower patient morbidity.     

Blood transfusion and renal allograft survival.

Thirty-two first renal transplantations with cadaveric allografts were reviewed to see how many of the recipients had received blood transfusions preoperatively. There was a significant difference in transplant survival between patients who had and patients who had not received blood transfusion before transplantation; this difference was entirely due to acute rejection within three months after transplantation in patients who had not received transfusion. Other factors studied had no effect on survival.     

Trimethoprim and Sulphamethoxazole in Typhoid Fever in Children

One hundred and three children with proved typhoid fever were treated with trimethoprim-sulphamethoxazole, and the results compared with those of a further 40 children treated with chloramphenicol. The bacteriological response to trimethoprim-sulphamethoxazole was unsatisfactory. From this study it seems that at present chloramphenicol is still the treatment of choice for typhoid fever. In view of the haematological changes occurring during therapy with trimethoprim-sulphamethoxazole caution is necessary and monitoring of the blood picture advisable, even at the recommended dose.     

Co-trimoxazole and Azathioprine: A Safe Combination

Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections and were treated with co-trimoxazole or another antibiotic in a controlled randomized prospective trial. The incidence of leucopenia in the group treated with co-trimoxazole (10·6%) was not significantly different from that in the group treated with other antibiotics (23·6%). Leucopenia when it occurred did so soon after transplantation at a time when the function of the renal transplant was poor in relation to the dosage of azathioprine given. In all cases the temporary withdrawal of azathioprine relieved the leucopenia despite continuation of the co-trimoxazole treatment. This study did not provide any evidence that co-trimoxazole plus azathioprine was a more potent cause of leucopenia than azathioprine alone.     

Late Failure in Cadaveric Renal Allografts

Sixteen patients with renal cadaveric allografts who have survived for one year or longer are reported. The patients were analyzed from the standpoint of incidence, quantity and course of proteinuria in relation to renal function and the nature of the original disease.This analysis shows that proteinuria is progressive and is accompanied by a decline in renal function when the original disease is of an immune nature. This was not so in patients with non-immune original disease. These findings suggest that recurrence of original disease plays an important role in late failure of cadaveric renal allografts.     

Suppression of Thymidine Uptake of Human Lymphocytes by Co-trimoxazole

Co-trimoxazole (trimethoprim-sulphamethoxazole) causes a decrease in the uptake of labelled thymidine in lymphocytes cultured in the presence of phytohaemagglutinin. This phenomenon was observed in 60% of 25 subjects. In cultures affected by the drug the mean suppression was 84%. A small decrease in thymidine uptake was noted with trimethoprim and sulphamethoxazole separately, but the effect was much more pronounced with the combination of the two drugs. The mechanism responsible for this phenomenon is discussed. The action is probably not due to the ability of these drugs to interfere with folic acid metabolism and it is likely that there is no direct effect on DNA synthesis.The suppression of thymidine uptake by lymphocytes in vitro in the presence of co-trimoxazole may not have any obvious clinical significance. However, in view of a report of an immunosuppressive action of trimethoprim in mice, it is possible that the leucopenia observed in some patients treated with this drug may have been caused by a similar mechanism.These experiments show that lymphocytes in vitro are suppressed by co-trimoxazole in concentrations comparable to, or smaller than, those found in vivo under normal therapeutic conditions. They are therefore likely to be clinically relevant.     

Kidney Preservation by Surface Cooling: Analysis of 130 Transplants

An analysis of 130 consecutive cadaveric renal transplants has shown the effectiveness of simple surface cooling of organs before transplantation. The primary graft failure rate was 10%, and kidneys could be stored for periods of up to 12 hours including warm ischaemia times of 150 minutes. Forty-eight patients received haemodialysis before transplantation and 78 patients received peritoneal dialysis. There were significant differences in the incidence of tubular necrosis in the two groups: these may have been linked to the differences in fluid and osmotic load presented to the transplants.     

Oral administration of recombinant human granulocyte-macrophage colony stimulating factor expressed in rice endosperm can increase leukocytes in mice

Human granulocyte-macrophage colony stimulating factor (hGM-CSF) is used clinically to treat leucopenia typically caused by cancer chemotherapy or radiotherapy. This study used multiple strategies to obtain very high expression levels of OsrhGM-CSF (14 mug/seed) in rice endosperm. Electron micrographs of immunogold-labeled transgenic endosperm showed that rhGM-CSF was not only localized in protein bodies but was also distributed in the apoplast. A biological activity assay indicated that OsrhGM-CSF stimulated the growth of TF-1 cells in vitro. In addition, the transgene was used to effectively treat leucopenia by oral administration of the unprocessed transgenic grains. In cyclophosphamide-induced leucopenic mice, transgenic seeds produced a 27% (t = 0.021) gain in leukocytes after 14 days feeding. Even in non-leucopenic mice, leukocyte gain was 37% (t = 0.002) more than that of mice fed non-transgenic seeds. This study provides a novel approach to the use of oral unprocessed transgenic OsrhGM-CSF seeds to treat leucopenia.     

Management of extra-pulmonary tuberculosis (excluding miliary and meningeal) in south and west Wales (1976-8).

In a retrospective survey of the management of extrapulmonary tuberculosis lymph node and genitourinary tuberculosis were found more commonly than bone and joint or gynaecological disease. Only 29% of patients received 18 moths'' chemotherapy while 31% received nine to 12 months'' treatment with rifampicin and isoniazid regimens and 34% had short-course chemotherapy with other regimens. Five patients were not offered any chemotherapy after diagnosis, and in five patients the diagnosis was overlooked because of administrative errors. One patient died from tuberculosis (renal). Poor drug compliance appeared less of a problem than in pulmonary tuberculosis. Only 14% of patients had their disease managed solely by consultants who were not specialists in chest disease. Liaison with a chest consultant did not necessarily ensure chemotherapy for 18 moths.     

Primary lymphoma of the heart

The authors describe the case of a 59-year-old woman, treated for breast cancer by mastectomy and chemotherapy 13 years before her death. Eleven years later she was treated successfully by gastric resection and chemotherapy for gastric cancer. In the last five months, the patient presented dyspnoea, leucopenia, hydropericardium and thoracic fluid both sides. In vivo the origin of these symptoms has not been discovered, neither by cytology nor by pleural biopsy.     

Toxicity of Trimethoprim-Sulphamethoxazole in Patients with Megaloblastic Haemopoiesis

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.     

Use of EQUORAL in de novo renal transplant recipients

This paper presents our experience to date with using a cyclosporine formulation Equoral (IVAX Pharmaceuticals) together with mycophenolate mofetil plus a steroid immunosuppressive regimen in the treatment of de novo renal transplant recipients. Ten cadaveric donor renal transplant recipients of mean age 51.6 years (range 37-66) were followed up over 6 months for the development of rejection attacks and side effects. All patients received prednisolone, mycophenolate mofetil (1 g/day during the first 5 days posttransplant and then 20 mg/kg/day) plus cyclosporine (3 mg/kg/day). Biopsy proven acute rejection episodes were observed in 2 out of 10 patients (20%). Six months patient as well as renal graft survival rate was 100%. The development of graft function was immediate after transplantation. The mean serum creatinine levels were gradually decreased. Over the 6-month posttransplant period, the function of the graft was satisfactory and stable. The majority of observed adverse events were those commonly reported with the use of cyclosporine and they resolved with a reduction in cyclosporine dose. Equoral treatment demonstrated an acceptable safety profile with maintenance of adequate renal function without incidence of malignancy/lymphoproliferative disease or serious infections. In conclusion, Equoral plus mycophenolate mofetil immunosuppression seems effective and safe on terms acute rejection rates, patient and renal graft survival rates and side profiles.     

Resistance of Haemophilus influenzae to Trimethoprim

Out of 210 isolates of Haemophilus influenzae obtained from the sputum of 63 patients with chronic respiratory infections 109 (52%) were resistant to trimethoprim-sulphamethoxazole by the disc test. The minimal inhibitory concentrations of trimethoprim for 17 out of 18 strains recorded as resistant were 10 μg/ml or higher. Resistant strains were isolated from time to time from 32 (82%) out of 39 patients known to have been treated with trimethoprim-sulphamethoxazole, compared with only 1 (12·5%) out of 8 patients known not to have been treated with this drug combination. Resistant strains were isolated most frequently from patients who had received long-term treatment. Since sulphamethoxazole penetrates from the blood into the bronchial secretions less readily than does trimethoprim it seems likely that the ratio of the two drugs in the bronchial tree is far from ideal. This may be an important factor in the use of these drugs for chest infections.     

不同化疗方案对晚期非小细胞肺癌患者骨髓抑制及免疫功能的影响

目的:探讨不同化疗方案对晚期非小细胞肺癌患者骨髓抑制及免疫功能的影响。方法:选取2011年1月至2013年12月收治的130例晚期非小细胞肺癌患者,按照知情同意原则随机分为三组:NP(长春瑞滨+顺铂)组45例、GP(吉西他滨+顺铂)组43例、TP(紫杉醇+顺铂)组42例,分别于化疗前及化疗2个周期后检测患者的骨髓抑制及免疫水平。结果:三种化疗方案进行治疗后骨髓抑制水平由高到低排列为GP组、TP组、NP组,差异有统计学意义(P0.05);GP组血小板减少发生率高于其他两组,TP组白细胞下降发生率高于其他两组,差异有统计学意义(P0.05);三组患者化疗后的免疫功能指标均较化疗前低,差异有统计学意义(P0.05)。三种化疗方案进行治疗后免疫功能抑制水平由高到低排列为GP组、TP组、NP组,差异有统计学意义(P0.05)。结论:GP组患者血小板下降更明显,TP组白细胞下降更为明显,NP组对骨髓抑制及免疫功能抑制较缓和,更适于老年人,因此临床选择化疗方案时要综合考虑患者骨髓状况、免疫功能情况及年龄等。     

The Impact of Delayed Chemotherapy on Its Completion and Survival Outcomes in Stage II Colon Cancer Patients

Background

Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients.

Patients and Methods

Patients (age ≥66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER–Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples.

Results

4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2–3 months), and 12.3% had delayed chemotherapy (≥3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival).

Conclusion

Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.     

Deaths from Occlusive Arterial Disease in Renal Allograft Recipients

In a series of 325 recipients of cadaveric renal transplants sudden occlusive arterial disease was found to be responsible for 12% of deaths. Acute myocardial infarction (9%) occurred 25 times more than expected in the normal population and cerebral thrombosis (3%) 300 times more. The greatest loss was in the initial three-month period after transplantation. Patients with renal failure due to essential hypertension were especially at risk, accounting for six of the 12 deaths.     

Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF(KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumor growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228.These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.     

Orally administered marine (1-->3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity

(1-->3)-beta-D-Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate their effects. The aim of this study was to evaluate both intraperitoneal and oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine showed significant stimulation of phagocytosis by peripheral blood cells. In addition, the efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was potentiated by Phycarine administration. Phycarine also strongly shortened the recovery of leucopenia caused either by chemotherapy or irradiation. Besides the role in stimulation of cellular immunity, we also found a significant increase of antibody formation. Using a suckling rat model for evaluation of the absorption and tissues distribution of enterally administered (125)I-Phycarine, we found that the majority of Phycarine was detected in the stomach and duodenum 5 min after the administration. This amount sharply decreased during first 30 min. A significant amount of Phycarine entered proximal intestine in a shortly after the gavage. Its transit through proximal intestine was decreasing with time and simultaneously increasing in the ileum. Systemic blood levels were very low (less than 0.5%). Taken together, these observations suggest that Phycarine is similarly effective both after i.p. and oral application, has very strong stimulating effects on three types of experimentally induced leucopenia and stimulates both humoral and cellular branch of immune reactions. The majority of Phycarine can be detected throughout the gastrointestinal tract, supporting the feasibility of enteral administration of Phycarine in the treatment of gastrointestinal diseases.     

Micro-organisms isolated from cadaveric samples of allograft musculoskeletal tissue

Allograft musculoskeletal tissue is commonly used in orthopaedic surgical procedures. Cadaveric donors of musculoskeletal tissue supply multiple allografts such as tendons, ligaments and bone. The microbiology laboratory of the South Eastern Area Laboratory Services (SEALS, Australia) has cultured cadaveric allograft musculoskeletal tissue samples for bacterial and fungal isolates since 2006. This study will retrospectively review the micro-organisms isolated over a 6-year period, 2006–2011. Swab and tissue samples were received for bioburden testing and were inoculated onto agar and/or broth culture media. Growth was obtained from 25.1 % of cadaveric allograft musculoskeletal tissue samples received. The predominant organisms isolated were coagulase-negative staphylococci and coliforms, with the heaviest bioburden recovered from the hemipelvis. The rate of bacterial and fungal isolates from cadaveric allograft musculoskeletal tissue samples is higher than that from living donors. The type of organism isolated may influence the suitability of the allograft for transplant.