Search

Background: Antenatal clinical practice guidelines recommend routine assessment of weight and provision of advice on recommended weight gain during pregnancy and referral to additional services when appropriate. However, there are barriers to clinicians adopting such best-practice guidelines. Effective, cost-effective, and affordable implementation strategies are needed to ensure the intended benefits of guidelines are realised. This paper describes the protocol for evaluating the efficiency and affordability of implementation strategies compared to the usual practice in public antenatal services., Method: The prospective trial-based economic evaluation will identify, measure, and value key resource and outcome impacts arising from the implementation strategies compared with usual practice. The evaluation will comprise of (i) costing, (ii) cost-consequence analyses, where a scorecard approach will be used to show the costs and benefits given the multiple primary outcomes included in the trial, and (iii) cost-effectiveness analysis, where the primary outcome will be incremental cost per percent increase in participants reporting receipt of antenatal care for gestational weight gain consistent with the guideline recommendations. Affordability will be evaluated using (iv) budget impact assessment and will estimate the financial implications of adoption and diffusion of this implementation strategy from the perspective of relevant fund-holders., Discussion: Together with the findings from the effectiveness trial, the outcomes of this economic evaluation will inform future healthcare policy, investment allocation, and research regarding the implementation of antenatal care to support healthy gestational weight gain., Trial Registration: Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12621000054819 (22/01/2021) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380680&isReview=true ., (© 2023. The Author(s).)

Context: Nutrition care is an effective lifestyle intervention for the treatment and prevention of many noncommunicable diseases. Primary care is a high-value setting in which to provide nutrition care., Objective: The objective of this review was to evaluate the cost-effectiveness of nutrition care interventions provided in primary care settings., Data Sources: Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials, EconLit, and the National Health Service Economic Evaluation Database (NHS EED) were searched from inception to May 2021., Data Extraction: Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guidelines. Randomized trials of nutrition interventions in primary care settings were included in the analysis if incremental cost-effectiveness ratios were reported. The main outcome variable incremental cost-effectiveness ratios (ICERs) and reported interpretations were used to categorize interventions by the cost-effectiveness plane quadrant., Results: Of 6837 articles identified, 10 were included (representing 9 studies). Eight of the 9 included studies found nutrition care in primary care settings to be more costly and more effective than usual care. High study heterogeneity limited further conclusions., Conclusion: Nutrition care in primary care settings is effective, though it requires investment; it should, therefore, be considered in primary care planning. Further studies are needed to evaluate the long-term cost-effectiveness of providing nutrition care in primary care settings., Systematic Review Registration: PROSPERO registration no. CRD42020201146., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Implementation of antenatal clinical guideline recommendations for addressing maternal alcohol consumption is sub-optimal. There is a complete absence of evidence of the cost and cost-effectiveness of delivering practice change interventions addressing maternal alcohol consumption amongst women accessing maternity services. The study sought to determine the cost, cost-consequence and cost-effectiveness of developing and delivering a multi-strategy practice change intervention in three sectors of a health district in New South Wales, Australia., Methods: The trial-based economic analyses compared the costs and outcomes of the intervention to usual care over the 35-month period of the stepped-wedge trial. A health service provider perspective was selected to focus on the cost of delivering the practice change intervention, rather than the cost of delivering antenatal care itself. All costs are reported in Australian dollars ($AUD, 2019). Univariate and probabilistic sensitivity analyses assessed the effect of variation in intervention effect and costs., Results: The total cost of delivering the practice change intervention across all three sectors was $367,646, of which $40,871 (11%) were development costs and $326,774 (89%) were delivery costs. Labour costs comprised 70% of the total intervention delivery cost. A single practice change strategy, 'educational meetings and educational materials' contributed 65% of the delivery cost. Based on the trial's primary efficacy outcome, the incremental cost effectiveness ratio was calculated to be $32,570 (95% CI: $32,566-$36,340) per percent increase in receipt of guideline recommended care. Based on the number of women attending the maternity services during the trial period, the average incremental cost per woman who received all guideline elements was $591 (Range: $329 - $940) . The average cost of the intervention per eligible clinician was $993 (Range: $640-$1928)., Conclusion: The intervention was more effective than usual care, at an increased cost. Healthcare funders' willingness to pay for this incremental effect is unknown. However, the strategic investment in systems change is expected to improve the efficiency of the practice change intervention over time. Given the positive trial findings, further research and monitoring is required to assess the sustainability of intervention effectiveness and whether economies of scale, or reduced costs of intervention delivery can be achieved without impact on outcomes., Trial Registration: The trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017)., (© 2021. The Author(s).)

Context: Improving maternal nutrition and promoting alcohol abstinence during pregnancy are key to reducing subsequent economic and social impacts. However, antenatal nutrition and alcohol interventions are underused, partly because economic evidence to support investment is limited., Objective: The purpose of this systematic literature review was to assess the extent to which economic evaluations have been applied to antenatal public health interventions, and implementation strategies addressing maternal nutrition and alcohol intake., Data Sources: Two separate systematic reviews were conducted to address the 2 stated aims. Both reviews adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The searches were conducted using the following databases: Medline, EMBASE, Cochrane, EconLit, CINAHL, and the National Health Service Economic Evaluation Database, accompanied by a handsearch of gray literature., Data Extraction: Review 1 returned 9599 records after duplicates were removed, from which 12 economic evaluations were included. Review 2 returned 136 records after duplicates were removed, with none eligible for inclusion. The articles included in review 1 comprised 10 economic evaluations of nutrition interventions and 2 evaluations of alcohol interventions., Data Analysis: Methodological quality was assessed using the Drummond 10-point quality checklist. Methodological quality was high, with variation in reporting practices and predominance of modeled evaluations., Results: Antenatal nutrition and alcohol interventions offer value for money and have potential to considerably reduce healthcare costs. No evidence regarding intervention implementation cost was identified., Conclusion: The current evidence base has important gaps that limit its value to decision makers. Incorporating health economic principles and methods into health promotion interventions will inform decisions about how to derive value from investment in healthcare., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite the known benefits of healthy eating in childhood, few Australian childcare services provide food that is consistent with dietary guidelines. The effectiveness of a web-based menu planning intervention to increase childcare service provision of healthy foods and decrease provision of discretionary foods in long day-care services in Australia was assessed in a randomised controlled trial. Here we consider the costs, consequences, cost-effectiveness and budget impact of the intervention using data collected within the trial., Methods: The prospective trial-based economic evaluation involved 54 childcare services across New South Wales (NSW), Australia. Services were randomised to a 12-month intervention or usual care. The intervention involved access to a web-based menu planning and decision support tool and online resources. Effectiveness measures included mean number of food groups, overall menu and individual food group compliance with dietary guidelines, and mean servings of food groups at 12 months. Costs (reported in $AUD, 2017/18) were evaluated from both health sector and societal perspectives. The direct cost to support uptake of the intervention was calculated, as were costs to each childcare service. The incremental cost of the intervention was calculated as the net difference in the cost to undertake menu planning and review plus the direct cost of the intervention. Incremental cost-effectiveness ratios (ICERs) including uncertainty intervals were estimated for differences in costs and effects between intervention and control groups. A relative value index was calculated to determine overall value for money., Results: Over the 12 months of the trial, we calculated a difference in cost between usual practice and intervention groups of - $482 (95% UI - $859, - $56). While the measured increase in menu and food group compliance within the trial did not reach statistical significance, there were significant improvements in mean servings of fruit and discretionary food, represented in the cost-consequence analysis. The calculated relative value index of 1.1 suggests that the intervention returns acceptable value for money for the outcomes generated., Conclusion: Compared to usual practice, web-based programmes may offer an efficient and sustainable alternative for childcare services to improve the provision of healthy foods to children in their care., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12616000974404.

The impact of pre-pregnancy obesity and maternal diet quality on the use of healthcare resources during the perinatal period is underexplored. We assessed the effects of body mass index (BMI) and diet quality on the use of healthcare resources, to identify whether maternal diet quality may be effectively targeted to reduce antenatal heath care resource use, independent of women's BMI. Cross-sectional data and inpatient medical records were gathered from pregnant women attending publicly funded antenatal outpatient clinics in Newcastle, Australia. Dietary intake was self-reported, using the Australian Eating Survey (AES) food frequency questionnaire, and diet quality was quantified from the AES subscale, the Australian Recommended Food Score (ARFS). Mean pre-pregnancy BMI was 28.8 kg/m 2 (range: 14.7 kg/m 2 -64 kg/m 2 ). Mean ARFS was 28.8 (SD = 13.1). Higher BMI was associated with increased odds of caesarean delivery; women in obese class II (35.0-39.9 kg/m 2 ) had significantly higher odds of caesarean delivery compared to women of normal weight, (OR = 2.13, 95% CI 1.03 to 4.39; p = 0.04). Using Australian Refined Diagnosis Related Group categories for birth admission, the average cost of the birth admission was $1348 more for women in the obese class II, and $1952 more for women in the obese class III, compared to women in a normal BMI weight class. Higher ARFS was associated with a small statistically significant reduction in maternal length of stay (RR = 1.24, 95% CI 1.00, 1.54; p = 0.05). There was no evidence of an association between ARFS and mode of delivery or "midwifery-in-the-home-visits".

Background: Antenatal clinical practice guidelines recommend routine assessment of women's alcohol consumption during pregnancy. The delivery of advice and referral when necessary are also recommended. However, evidence suggests there are barriers to the uptake of best-care guidelines. Effective, cost-effective and affordable implementation strategies are needed to ensure the intended benefits of guidelines are realised through addressing identified barriers. This paper describes the protocol for evaluating the efficiency and affordability of a practice change intervention compared to the usual practice in an implementation trial., Methods: The effectiveness of the intervention will be evaluated in a stepped-wedge randomised controlled implementation trial, conducted in an Australian setting. An economic evaluation will be conducted alongside the trial to assess intervention efficiency. A budget impact assessment will be conducted to assess affordability. The prospective trial-based economic evaluation will identify, measure and value key resource and outcome impacts arising from the multi-strategy practice change intervention compared with usual practice. The evaluation will comprise (i) cost-consequence analyses, where a scorecard approach will be used to show the costs and benefits given the multiple primary outcomes included in the trial, and (ii) cost-effectiveness analyses, where the primary outcome will be incremental cost per percent increase in participants reporting receipt of antenatal care for maternal alcohol consumption consistent with the guideline recommendations. Intervention affordability will be evaluated using budget impact assessment and will estimate the financial implications of adoption and diffusion of this implementation strategy from the perspective of relevant fundholders. Results will be extrapolated to estimate the cost and cost-effectiveness of rolling out the model of care., Discussion: Uptake of clinical guidelines requires practice change support. It is hypothesized that the implementation strategy, if found to be effective, will also be cost-effective, affordable and scalable. This protocol describes the economic evaluation that will address these hypotheses., Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12617000882325. Registered on 16 June 2017., Competing Interests: Competing interestsMK, ED, KC, LW and JW receive salary support from the Hunter New England Clinical Services Nursing and Midwifery, which contributes funding to the project outlined in this protocol. MK receives salary support from a NHMRC Translating Research Into Practice (TRIP) Research Fellowship (APP1150476). EJE is supported by a NHMRC Medical Research Futures Fund Practitioner Fellowship (APP1135959) and NHMRC CRE (APP1110341). All other authors declare that they have no competing interests., (© The Author(s) 2020.)

The maternal diet influences the long-term health status of both mother and offspring. The current study aimed to compare dietary intakes of pregnant women compared to food and nutrient recommendations in the Australian Guide to Healthy Eating (AGHE) and Nutrient Reference Values (NRVs). Usual dietary intake was assessed in a sample of women in their 3rd trimester of pregnancy attending antenatal outpatient clinics at John Hunter Hospital, Newcastle, New South Wales (NSW). Dietary intake was measured using the Australian Eating Survey, a validated, semi-quantitative 120-item food frequency questionnaire. Daily food group servings and nutrient intakes were compared to AGHE and NRV targets. Of 534 women participating, none met the AGHE recommendations for all food groups. Highest adherence was for fruit serves (38%), and lowest for breads and cereals (0.6%). Only four women met the pregnancy NRVs for folate, iron, calcium, zinc and fibre from food alone. Current dietary intakes of Australian women during pregnancy do not align with national nutrition guidelines. This highlights the importance of routine vitamin and mineral supplementation during pregnancy, as intakes from diet alone may commonly be inadequate. Future revisions of dietary guidelines and pregnancy nutrition recommendations should consider current dietary patterns. Pregnant women currently need more support to optimise food and nutrient intakes.

Since the mid-2000s stepped care, a model of integrated healthcare delivery, has been promoted for offering accessible, effective and efficient services for individuals with mental health conditions. However, adoption of the model has not been widespread warranting additional investment by way of implementation strategies to encourage uptake. These strategies also require funding and their value for money should be assessed to inform decision making and practice. We conducted a review to better understand the extent to which the cost-effectiveness of stepped care has been evaluated (review i) and also to investigate whether economic evaluation has been applied to implementation strategies of stepped care services for anxiety and depression in developed (high income) countries and to chart their methods and outcomes (review ii). The searches were conducted in six electronic databases, grey literature and relevant journals. The search strategies returned two papers for reviews (i) and a single paper for review (ii). Despite stepped care models of integrated mental health service provision being promoted as optimal, there is limited knowledge surrounding the real-world cost-effectiveness of their application and clearly a need for good quality economic evaluations of integrated care that comply with international guidelines of good practice. There is even less information pertaining to the cost-effectiveness and budget impact of strategies designed to increase the uptake of these models., Competing Interests: The authors have no competing interests to declare.

Acute graft rejection and delayed function are considered to be the major risk factors of short-term as well as long-term graft survival. We studied the impact of these factors on graft outcome among 109 renal transplant recipients. All recipients were treated with triple drug protocol. The recipients were divided into two groups: I group included 57 patients with delayed graft function (DGF), II group included 52 patients with immediate graft function (IGF). We studied graft survival, incidence of acute rejection, serum creatinine levels and the cause of graft loss for patients in both groups. Acute rejection episodes occurred in 49% of patients from DGF group and 45% of patients from IGF group. Graft survival in IGF group was better than in DGF group. Actuarial graft survival at 1, 2, 3 and 4 years in examined groups was 84%, 82%, 72%, 65% vs. 92%, 86%, 84%, 84%, respectively. One-year graft survival in patients with acute rejection from DGF group and IGF group was significantly lower than in patients who remained rejection free (69%, 74% vs. 94%, 96%). We concluded that delayed graft function decreases long-term graft survival, while immediate graft function has an excellent impact on graft outcome. Acute graft rejection is the strongest risk factor of graft loss.

A 64-year-old man presented with symptoms of systemic immune disease dominated by rapidly progressive glomerular injury with highly positive ANCA of cytoplasmic distribution. The clinical course was characterized by dependence upon the intensity of immunosuppression, which has finally led to development of fungal septicaemia and death. The post mortem examination revealed occult gastric cancer with regional lymphatic involvement and crescentic glomerulonephritis, while failing to substantiate clinical findings of systemic vasculitis. This is, to our knowledge, the first case of ANCA-positive glomerulonephritis accompanying visceral malignancy and as such raises the question of whether it results from a simple coincidence or a causal relationship.

Deoxyribonucleases activity in T and B lymphocytes isolated from 45 patients with chronic renal failure and 30 control subjects was measured. The results obtained clearly show a dramatic increase in enzyme activity in both T and B lymphocyte cells isolated from uraemic patients when compared with the control cell. The increase in enzyme activity was limited to the group of relatively small nucleases ranging from 14 kDa to 18 kDa. Since it was shown previously that these nucleases are among the cleavage products of the largest subunit of DNA-dependent RNA polymerase class I, it is suggested that a characteristic feature of the lymphocyte cell isolated from uraemic patients is increase of RNA polymerase lability, thus resulting in RNA synthesis decrease. Amongst toxins increasing catabolism of the active polymerase enzyme, a significant correlation with the vise of lymphocyte Mg2+ and Mn2+ ions was disclosed.

The DNA-dependent RNA polymerase activity and endonucleases in uraemic lymphocyte cells were investigated. It was found that the activity and quantity in three classes of polymerases are remarkably reduced. The reduction in enzyme activity is accompanied by increasing endonuclease activity. The relationship of polymerase enzymes with endonucleases is discussed.

The nuclease activity in T and B lymphocytes isolated from patients with chronic renal failure and control subjects was studied. The data obtained show a slight increase in nuclease activity in T and B cells isolated from uraemic patients as compared to the control cells. The increase in enzyme activity was limited to the group of relatively small nucleases with molecular weights ranging from 14 kDa to 18 kDa. It was documented previously that these nucleases are among the cleavage products of the largest subunit of DNA-dependent RNA polymerase I, which is responsible for ribosomal RNA synthesis. Thus, we suggest that the characteristic feature of lymphocytes isolated from uraemic patients is lowering of their metabolic activity. Amongst toxins increasing catabolism of the active enzyme, a significant correlation with the rise of lymphocyte Mg2+ and Mn2+ ions was disclosed.

Deoxyribonucleases and DNA-dependent RNA polymerase activities in T and B lymphocytes isolated from patients with chronic renal failure and control subjects were studied. The data clearly shows that the nuclease activity in T and B cells isolated from uraemic patients is remarkably enhanced when compared to the control cells. Concomitant with the enhancement in enzyme activity, the reduction in RNA polymerase I activity and quantity was observed. It was found that the increase in nuclease activity and quantity was limited to the group of relatively small nucleases with molecular weights ranging from 14 kDa to 18 kDa. It has been reported previously that these nucleases are among the cleavage products of the largest subunit of DNA-dependent RNA polymerase I. Thus we suggest that the depressed metabolic activity is a characteristic feature of the uraemic lymphocyte cells and the observed increased in DNase activity in those cells is a result of polymerase I degradation.

Deoxyribonuclease (DNase) activity and metal ion concentrations in lymphocytes of patients with chronic renal failure and in healthy controls were studied. The data suggest that T and B lymphocyte nuclei of patients with renal failure show increased DNase activity when compared to their healthy counterparts. It is suggested that the enhancement of enzyme activity is a result of increased metal ion concentration rather than increased enzyme copy count. The data strongly suggest that haemodialysis of uraemic patients is more effective for improvement of lymphocyte metabolism than the conservative chemical treatment.

In attempt to avoid a detrimental synergism between CsA and renal ischemia in the immediate postoperative period, ALG (425 lymphocytotoxic units/kg) with small doses of CsA (6-8 mg/kg) and P were applied as the initial immunosuppressive therapy in 14 recipients of cadaveric kidneys. ALG was administered for 5 to 14 days and 2 days before withdrawing ALG, Aza (2 mg/kg) was introduced. Results of this protocol were compared with those of 19 pts treated with CsA (12 mg/kg) and P. All the pts were followed for at least 12 months. The duration of posttransplant anuria was significantly reduced in the ALG/CsA/P group (p < 0.02). The sCr concentration after 12 months of observation was significantly lower (p < 0.05), no alterations in urinalysis were detected, the number of hypertensive pts was decreased. The acute rejection rates were equivalent in both groups, however 3 of 4 rejections in ALG/CsA/P group were resistant to steroids and occurred in pts with shortened period of ALG administration. The one year patient and graft survival in the ALG/CsA/P and control groups were respectively: 78.5%, 71.4% and 89.4%, 78.9%. Severe infectious complications in the group treated with ALG/CsA/P occurred in pts who were subsequently treated with OKT3.

The activity of nucleases and concentrations of highly important metal ions in T and B lymphocytes were examined. The source of lymphocyte was the blood of patients with chronic renal failure and activity of enzyme as well as ion concentrations were compared to the control group. Concomitant with the increase in enzyme activity was an increase of metal ion concentrations assayed in both T and B lymphocytes isolated from patients with renal disease. The data suggest that the enhancement of nuclease activity is a result of increased enzyme polypeptide synthesis and its stimulation by metal ions. Utilization of the nuclease test for monitoring uraemic toxicity is considered.

We investigated the activity of some enzymes of the transcriptive DNA system to assess lymphocyte metabolic potential in patients with proliferative glomerulopathies. This study included analysis of the activity of three classes DNA-dependent RNA polymerases, before and 6 months after immunosuppressive therapy (Azathioprine + Prednisone). The enzyme activity was measured in nuclear extracts of T and B lymphocytes by estimation of the uptake of 3/H/UTP in the presence of alpha-amanitine. The immunoblotting technique using anti-polymerase I antibodies and nuclear proteins separation with immobilized exogenous DNA were employed to assess a type of the increase of the DNA-dependent RNA polymerase activity in lymphocytes populations (enhancement of the synthesis or limited depolymerization and degradation of the active enzyme). We found that the RNA polymerizing activity was increased in both lymphocyte populations. In T lymphocytes the increase was caused by an enhanced activity of transcript DNA enzymes, secondary to increased gene expression. In B lymphocytes an increase in enzyme activity was rather due to large stability RNA-polymerases in these cells. DNA-dependent RNA polymerase I in T and B cells was not modified by immunosuppression, while reduction in enzymatic activity of the remaining RNA-polymerase classes in T lymphocytes depends on partial limitation of their gene expression. Our study indicates that profound and various lymphocyte metabolic changes occur in patients with proliferative glomerulonephritis resulting from modifications in a gene expression and initiation of DNA synthesis in these cells.

The effect of uremia on the activity of the erythrocyte complement receptors type 1 (CR1), and the changes occurring after renal transplantation, were studied. The complement receptor activity was measured by immune adherence utilizing a rosette technique. Patients with terminal kidney failure on the hemodialysis program exhibited significantly lower values of the erythrocyte CR1 activity in comparison with healthy controls. The circulating immune complexes did not affect erythrocyte CR1 activity. After successful renal transplantation, irrespective of the immunosuppressive program used, a significant increase in erythrocyte CR1 activity appeared, similar to control group values. However, the activity of erythrocyte CR1, in the graft recipients under cyclosporin A treatment, was significantly higher than in the patients receiving azathioprine with prednisone. Therefore, it is possible that cyclosporin A, transported in the erythrocytes, modifies the complement receptor function.

A study was carried out to verify the clinical usefulness of the elaborated method for the measurement of antistreptococcal antibody in revealing the streptococcal etiology of glomerulonephritis. In 158 patients with glomerulonephritis antistreptococcal antibody (ASA), circulating immune complexes (CIC) and haemolytic activity of the complement were measured. On the basis of immune complex formation it has been concluded that streptococcal infection may cause glomerulonephritis. Serial determinations of ASA and CIC are helpful in establishing the streptococcal etiology of glomerulonephritis and in monitoring the course of the disease.

Monocytes of 95 patients with chronic glomerulonephritis (ch.g.) tested in vitro demonstrated characteristics of activation in proliferative, and of functional suppression in mesangiocapillary glomerulopathy. Fc and C3 receptor function studied by rosette assay and metabolic potential measured by the NBT reduction test constituted result patterns. Receptor tests were supplemented with their counterparts after monocyte triggering with heat-inactivated sera and in case of NBT assay - stimulation with zymosan. Membranous, minimal change, mesangial and focal glomerulonephritis monocytes presented less specific configurations of data than those of proliferative and mesangiocapillary, with a uniform increase of trypsin-resistant Fc receptor activity. There was no appreciable correlation between the presence of circulating immune complexes (c.i.c.) in patient sera and parameters tested. The mesangiocapillary "suppression pattern" suggests mononuclear phagocyte defect in this glomerulopathy.

Studies on the adenosine deaminase (ADA) and aldolase activities in lymphocytes were performed in 67 patients with glomerulonephritis (gn) and in 20 healthy individuals from the control group to get an insight into the lymphocyte metabolism. Statistically significant decrease of ADA activity was found in the groups of patients with chronic proliferative gn, membranoproliferative gn, membranous gn and lupus nephritis in comparison with the healthy individuals from the control group. As far as decrease of aldolase activity is concerned it has reached statistical significance in patients with mesangial gn, membranoproliferative gn, membranous gn and lupus nephritis. The lymphocyte metabolism did not show any abnormalities in the enzymatic indicators only in patients with acute proliferative gn and submicroscopic gn. The activity comparison between both enzymes in the lymphocytes, contrasted on the basis of high and low clinical dynamics of gn, revealed a tendency to lower ADA and aldolase activities in patients with high clinical dynamics. However, this difference was at the limit of statistical significance (p less than or equal to 0.10).

The effect of immunosuppressive and anti-inflammatory drugs on the T and B lymphocyte populations, as well as cellular hypersensitivity in relation to GBM antigens (measured by MIF activity) in 60 patients with different types of glomerulopathy has been tested. The results were compared with a control group of 47 untreated patients and 32 healthy subjects. The treatment was carried out using the following drugs: azathioprine, cyclophosphamide, prednisone, ibuprofen and indomethacin. In a sample of 14 patients receiving ibuprofen and in 7 receiving arathioprine, indomethacin and prednisone, the T and B lymphocyte kinetics as well as MIF activity were repeatedly tested before and during the treatment of 150 days. In the patients under this treatment, a decreased percentage of lymphocytes with receptors for a complement as well as, in some cases. MIF suppression was observed. A comparison of healthy subjects and untreated patients with a group of 39 subjects tested for T and B lymphocytes as well as MIF activity after several months of the above treatment was made. It was found that supportive therapy with azathioprine and prednisone led to a normalization of B lymphocytes (EA and EAC rosettes) and to a small increase of T lymphocytes number. On the other hand, treatment with indomethacin and ibuprofen led to an increased B lymphocyte count (EA and EAC rosettes). Cyclophosphamide given with azathioprine caused a decrease in the proportion of T lymphocytes and an increase in the number of null cells. In addition, it was found that immunosuppressive drugs as well as anti-inflammatory drugs, even when administered in supportive doses caused in some cases, the suppression of cellular immunity as measured by MIF activity.

The aim of this work was to determine the activity of helix-destabilizing protein (HD-protein), which is indispensable in basic genetic processes such as DNA replication, genetic recombination and transcription, in lymphocytes of patients with different morphological types of glomerulonephritis and with chronic renal insufficiency, treated conservatively and by maintenance hemodialysis. The estimation was done on 44 patients with glomerulonephritis and on 20 patients with chronic renal insufficiency. The control group consisted of 20 healthy individuals. The investigations prove the fact that in human lymphocytes helix-destabilizing protein occurs, and its quantity enables us to determine its activity in the diseased and healthy state. Measurement of HD-protein activity seems to be a good marker of the altered lymphocyte function. Especially high HD-protein activity was noticed in cases of acute glomerulonephritis, lupus glomerulonephritis and in the active forms of chronic glomerulopathies. Generally, the tested parameter showed a positive correlation with the activity of the glomerulonephritic process. In lymphocytes of patients with chronic renal insufficiency treated conservatively, a greater activity of helix-destabilizing protein occurred than in the control group. Lymphocytes from patients with chronic renal insufficiency, treated with repetitive maintenance hemodialysis, did not reveal significant differences in HD-protein activity, determined directly before hemodialysis and after its completion, in comparison to the control group of healthy individuals.

143 patients were evaluated clinically on the basis of the renal biopsy. Three methods for detecting circulating immune complexes (CIC) were employed: complement consumption test, inhibition of erythrocyte antibody IgG-EA rosette forming test and optical density of 4% PEG precipitated sera. CIC were present in the sera of all patients with acute poststreptococcal glomerulonephritis (2 weeks after streptococcal infection of the throat). In a group of patients with chronic glomerulonephritis the highest values in positive results were observed in lupus nephritis, chronic proliferative glomerulonephritis and chronic submicroscopic glomerulonephritis. These results were compared with levels of total hemolytic complement, C3, C4 components and serum immunoglobulins (IgA, IgG, IgM).

A total of 234 patients with chronic glomerulonephritis, detected on the basis of clinical, immunological and pathomorphological criteria, have been examined. A group of 23 chronic glomerulonephritis patients with massive deposits of immunoglobulin A found by immunofluorescent examination, has been separated on the basis of immunohistochemical studies. In this group, occurrence of different morphological forms of glomerulonephritis has been observed: 30.4% mesangial-proliferative glomerulonephritis, 13% submicroscopic glomerulonephritis and one case of membranous glomerulonephritis. Complete haemolytic activity of complement, level of complement components C3 and C4, immunological complexes circulating in blood, properdin and immunoglobulin A levels, fibrin and fibrinogen (FDP) degradation product concentrations and their 24-hour excretions with urine have been determined. Preliminary observations of this group of patients seem to indicate a positive effect of steroid therapy in glomerulonephritis with IgA deposits, irrespective of the morphological form of the disease.

The hemodialysis program was carried out in four male chronic schizophrenic patients hospitalized 3--12 months in the Psychiatric Clinic, Medical University, Wroclaw. The diagnosis was made independently by three psychiatrists. The disease lasted 5 to 26 years. The clinical assessment of mental and physical state followed each dialysis. The BPRS, CGI and Wing's Ward Behavior Scale were filled. Eleven to 20 dialyses were conducted once a week (two patients) or twice weekly (two patients). Neuroleptics were withdrawn. A short period of slight, unspecific improvement was followed by a deterioration in all cases, which made it necessary to put the patients back on neuroleptics. At the end of the dialysis program none of the patients improved. Further research on the efficacy of dialysis in chronic schizophrenia should be made before the final assessment of its value.

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.

The effect of acute experimentally induced renal failure after intramuscular injection of glycerol on serum and urine GGTP, LAP and AP activities was studied in 30 rabbits. High doses of glycerol caused shock, myolysis and hemolysis, leading to acute renal insufficiency. Serum urea and creatinine levels significantly increased, there was proteinuria, and significant decrease in 24-hr diuresis, glomerular filtration, and urinary urea excretion. The changes in LAP and AP activities were significant, and in GGTP-nonsignificant. In the urine GGTP and LAP increased significantly, and AP nonsignificantly. Urinary excretion of AP increased significantly, and GGTP and LAP nonsignificantly. The highest activity and urinary excretion of GGTP and LAP were observed on the 2nd day, and of AP--on the 5th day of renal failure.

In vitro reactivity of lymphocytes to phytohemagglutinin (PHA) and pokeweek mitogen (PWM) was studied in 17 patients with chronic glomerulonephritis treated systematically over many months (average, 23 months) with immunosuppressive drugs (prednisone, indomethacin, azathioprine, cyclophosphamide). Blastic transformation of lymphocytes in cultures stimulated with PHA was tested three times: before beginning of treatment, during the course of therapy with full doses, and after prolonged ambulatory treatment with maintenance doses. The degree of blastic transformation under the influence of PWM was determined only after periods of many months of treatment with chemical immunosuppresors. The results showed that neither treatment of chronic glomerulonephritis for several weeks with full doses, nor subsequent prolonged administration (for periods of tens of months) of maintenance doses of immunosuppresors regularly inhibit blastic transformation of lymphocytes stimulated with PHA. Similar observations were made using PWM after many months of immunosuppressive therapy. Reactivity of lymphocytes to PWM in all patients resembled reactivity to PHA.

Studies were performed on 79 subjects, out of which 32 belonged to the control group and 47 suffered from glomerulonephritis. The number of T and B lymphocytes in peripheral blood was determined using the technique of E, EA and EAC-rosette tests. Also, the lymphocyte blast response to non-specific mitogens (PHA, Con A, PWM) was established in vitro. Patients suffering from acute proliferative glomerulonephritis, as compared to the control group, displayed a statistically significant increase of lymphocytes with the receptor for complement (EAC-rosettes). Their reactivity to all three mitogens did not differ from the values obtained in the control group. In patients suffering from chronic glomerulonephritis (proliferative, membranous-proliferative, membranous), shiftings in the contents of the peripheral blood lymphocytes pools were of opposite directions, i.e., statistically significant in comparison with the control group. Also an increase in the absolute number of T lymphocytes (E-rosettes) was observed. Generally speaking, the values of blast transformations after mitogen stimulations were smaller in patients suffering from chronic than in those suffering from acute glomerulonephritis. In 1/3 of them, the decrease of blast response to one of the three mitogens was detected. The decrease exceeded the lower limit of values of healthy subjects, and most often, it was connected with Con A stimulation.

The only effective management of life-threatening hypervolemia in course of terminal renal failure is dialysis or hemofiltration. Nonetheless we succeeded in attenuating hypervolemic pulmonary edema utilizing low doses of Captopril in three patients awaiting entry into the maintenance hemodialysis program. The drug added to diuretic and, in two cases, digitalis therapy enabled pharmacologic management of patients volume overload for 12-25 days before the dialysis treatment could be started. No further decline in renal function or other side effects of Captopril were encountered. We conclude that Captopril may be life-saving in settings requiring pharmacologic relief of uremic pulmonary edema.

Blastic transformation of peripheral blood lymphocytes following stimulation with phytohemagglutinin during immunosuppressive therapy (prednisone 2 mg/kg body weight, indomethacin 2--3-5 mg/kg, azathioprine 2--4 mg/kg, cyclophosphamide 1-5--3 mg/kg per day) was studied in 59 patients with various morpholigic forms of chronic glomerulonephritis and in 7 with lupus erythematosus nephritis. No uniformly regular influence of immunosuppressive therapy in the doses employed in glomerulonephritis on blastic transformation in in vitro cultures was noted. The specific drug administered was not decisive for the character of the change in reactivity of lymphocytes (increase or decrease in blastic transformation). The interesting observation was made that efficacy of treatment was high in patients with lowest initial values of blastic transformation and its greatest increase during therapy. Apparently, disorders of cellular immunity assessed on the basis of blastic transformation of lymphocytes stimulated with phytohemagglutinin are not a decisive prognostic factor in glomerulonephritis. The results are discussed from the aspect of a possible influence of immunosuppressive therapy on restoration of the physiological proportion of T and B lymphocytes in peripheral blood.

The function of polymorphonuclear neutrophils in two groups of patients with glomerulonephritis was investigated. Patients were divided according to renal efficiency. In the group of 37 patients with renal failure a decrease in chemotactic activity, phagocytal index and iodination activity of leukocytes was observed (as compared with the control group). Our data indicate that renal insufficiency has some influence on the activity of polymorphonuclear neutrophils.

The EACA, known for its antihemorrhagic potential, has also been demonstrated to mitigate physiopathologic reactions linked activation of serum proteolytic cascades. Herein, we present results of experiments exploring a possible modification of nephrotoxic serum nephritis (NSN) in rats by the EACA. A combined intraperitoneal and oral administration of EACA to Lewis rats with the NSN (1 g/kg/12 h and 1 g/kg/24 h, respectively), significantly reduced albuminuria (p less than 0.05 EACA-treated rats vs. rats obtaining vehicle alone, days 2-3), enhanced endogenous creatinine clearance (ECC) - (p less than 0.01 - day 3) and attenuated renal histopathologic changes (day 3 post induction). The EACA given to control healthy rats did not cause any notable changes in the above parameters. We conclude that the EACA considerably diminishes the intensity of acute nephritis induced in rats by a nephrotoxic heteroantiserum.