A cross-sectional, face-to-face, community survey of mental health and deprivation in post-recession Ireland: a rising tide lifts all boats?

OBJECTIVE: To assess community mental health in suburban Dublin in 2018, 5 years after Ireland's economic recession ended. METHODS: A cross-sectional, face-to-face, household survey was conducted in a random cluster sample of 351 households in Tallaght, a deprived suburb of Dublin. RESULTS: A majority of respondents (61.3%) reported stress over the previous 12 months, with a higher rate in areas of high (66.9%) compared to lower deprivation (55.5%). Deprivation was not related to rates of loneliness (20.2%), feeling depressed (20.2%), loss of interest (19.7%) or anxiety (22.5%). Mean score for positive mental health (59.3/100, with a higher score indicating better mental health) was lower than that reported in a national sample in 2007 (68/100); positive mental health was associated with not living with a person with chronic illness, self-identifying as 'non-Irish' and greater age. Mean score for psychological distress (76.7/100, with a higher score indicating less distress) was also lower than that in 2007 (82/100); less psychological distress was associated with not living with a person with chronic illness or disability, greater age and identifying as non-Irish. The rate of 'probable mental illness' over the previous 4 weeks (13.1%) was higher than in 2007 (7%). CONCLUSIONS: Our findings emphasise the high prevalence of stress, especially in deprived suburban areas; the centrality of carer burden in determining mental wellbeing; and associations between positive mental health on the one hand and greater age and identifying as non-Irish on the other.

Green tea polyphenol epigallocatechin gallate inhibits cell signaling by inducing SOCS1 gene expression.

Therapeutic effects of green tea involve an inhibitory function of its constituent polyphenol epigallocatechin gallate (EGCG) on cell signaling. The specificity and mechanism(s) by which EGCG inhibits cell signaling have remained unclear. Here, we demonstrate that green tea and EGCG induce suppressor of cytokine signaling 1 (SOCS1) gene expression, a negative regulator of specific cell signaling pathways. In mouse immune cells, EGCG induces SOCS1 expression via an oxidative (superoxide) pathway and activation of the signal transducer and activator of transcription 5 transcription factor. EGCG inhibited SOCS1-regulated cell signaling, but this inhibitory effect was abrogated in cells deficient in SOCS1. These findings identify a mechanism by which EGCG inhibits cell signaling with specificity, mediated by induction of the negative regulator SOCS1.

End-stage renal disease after kidney donation: a single-center experience.

PURPOSE: Although the risk of kidney donation has been determined in many studies to be low with respect to morbidity and mortality, it is important to keep in mind that patients are put at some risk when they donate an organ for transplantation. The reported incidence of end-stage renal disease (ESRD) among kidney donors ranges from 0.2% to 0.5% with varying follow-up times. Herein, we have reported four living kidney donors at our institution who progressed to ESRD. MATERIALS AND METHODS: We reviewed registry data and medical records of patients who underwent donor nephrectomy at our institution between October 1, 1959, and June 30, 2005, particularly cases who developed ESRD. RESULTS: Between October, 1959, and the end of June, 2005, 3591 kidney transplants were performed at our center including 1195 of the organs (33%) from living donors, whose mean age was 41.9 years. Four kidney donors (0.33%) developed ESRD. Their mean age at donation was 31 years; the mean age at ESRD development was 46.5 years. All four patients donated to siblings with renal failure. Two of the four (50%) had another first-degree relative who subsequently developed renal failure. Two of the four (50%) smoked tobacco subsequent to donor surgery, and one (25%) was obese. CONCLUSIONS: Progression to ESRD is rare among living renal donors. Kidney donation is safe when strict eligibility criteria are met. There may be an increased risk for progression to ESRD among donors with a family history of renal disease.

Community-based, cross-sectional study of self-reported health in post-recession Ireland: what has changed?

BACKGROUND: Health has a complex relationship with economic conditions. Ireland's economic recession (2008-13) and sharp recovery (from 2014 onwards) offer a valuable opportunity to study self-reported health and its correlates in the context of rapid economic change. AIM: To assess the correlates of self-reported health in Dublin, Ireland after the economic recession of 2008-13. DESIGN: Cross-sectional, face-to-face household survey using random cluster sampling. METHODS: Self-reported health and its correlates were assessed in randomly selected households in Tallaght (a suburb of Dublin) and results were compared with a similar survey in 2014. RESULTS: Five hundred and eighty-three eligible households were invited to participate and interviews were completed in 351 (response rate: 60.2%). The proportion of respondents rating their health as 'very good' or 'good' was 71.8%, essentially unchanged from four years earlier (70.8%). In 2018, better self-reported health was associated with less stress, holding private health insurance, not living with a person with a disability or chronic illness, and greater education; taken together, these factors explained 39.4% of variation in self-reported health. Unlike 2014, self-reported health in 2018 was no longer directly associated with employment status. CONCLUSIONS: Self-reported health has stabilized in Ireland since the end of the economic recession, but its correlates have shifted. Stress and carer burden are now among the strongest correlates of poor self-reported health in Ireland.

Nutritional support at the end of life: the relevant ethical issues.

This article attempts to summarize the ethics of nutritional support at the end of life. Although ethics are timeless, they have to be applied or adapted to new situations arising from our ability to prolong life by the application of relatively new nutritional treatments. The application of the law, and guidance from professional bodies on withholding or withdrawing treatment remains an emotive challenge for all involved in nutritional care and for society as a whole.

RNA synthesis in nuclei isolated from early embryos of Xenopus laevis.

1. Rates of RNA synthesis in isolated Xenopus embryo nuclei decrease from blastula through gastrula and neurula stages to hatching tadpoles. 2. In blastula and gastrula nuclei, net synthesis of RNA continues for over 30 min, both in the presence of KCl at 0.4 M and in its absence. In nuclei from later stages, net synthesis continues for only about 10 min in the absence of KCl. 3. At low ionic strength, RNA synthesis in all nuclei is greater with optimum Mg-2+ (6 mM) than with optimum Mn-2+ (1 mM). At high ionic strength the reverse is true. 4. An unusual feature, which gradually disappears as development proceeds, is that curves relating RNA synthesis to KCl concentration show a peak at 0.1 M KCl. In blastula nuclei, RNA synthesis is more rapid at 0.1 M KCl than at 0.4 M. 5. This peak at low ionic strength is not observed in the presence of the initiation inhibitor rifamycin AF/013. It is concluded that the peak arises from initiation of RNA synthesis by an excess of RNA polymerases bound non-specifically to the isolated nuclei. The residual synthesis, representing elongation of chains that were initiated in vivo, still declines as development progresses. 6. In blastula nuclei, over half of the RNA synthesis is effected by polymerase II (inhibited by alpha-amanitin), the proportion remaining roughly constant with increasing ionic strength. In neurula nuclei, the proportion rises from about one-half to three-quarters. The initiation-dependent peak in blastula and gastrula nuclei is contributed by both alpha-amanitin-sensitive and alpha-amanitin-resistant enzymes.

Ion binding and chromatin condensation.

1. The binding of 45Ca2+ to hen erythrocyte chromatin has been studied to help elucidate how cations induce a reversible condensation of this chromatin. 2. As the unbound Ca2+ of the medium rises from 0.5 to 4 mM, Ca2+ is bound to the chromatin with a stability constant of approx. 3.1 and a saturation value of 0.25 Ca2+ per DNA phosphate, or one-half the value for pure DNA. Condensation of the chromatin is half complete when this binding of calcium is roughly half complete. Hence the transition from the uncondensed to the condensed state occurs as repulsion between the free DNA phosphates of erythrocyte chromatin is neutralised by bound cations. Genetically active chromatin may be maintained in an uncondensed state in living cells by the presence of different negative groups that remain unneutralised at the unbound cation concentrations of the cell. 3. That only one-half of the calcium binding sites of DNA are masked in erythrocyte chromatin supports recent models of chromatin structure in which the DNA double helix is wound round a core of histones. 4. Competition for calcium binding sites in the chromatin by other cations was also studied.

Can home parenteral nutrition be provided by non-specialised centres? 2300 weeks of experience at a district general hospital in the United Kingdom.

BACKGROUND & AIMS: Home Parenteral Nutrition (HPN) is an accepted treatment of intestinal failure but is mostly restricted to a few large specialist centres in the UK. The provision of high-quality HPN is of paramount importance to patients with intestinal failure, but its restriction to large specialist centres limits the number of patients who can receive it. The study aim was to determine if HPN can be effectively administered in a non-specialist centre. METHODS: Adult HPN patients at a single District General Hospital in the United Kingdom were analysed by indications, complications and outcome. RESULTS: 2310 patient weeks of HPN were provided to 23 patients, aged 18-80 years with intestinal failure. Catheter infection rate was 0.315 per patient year, with one patient excluded due to persistent nasal digitation. Patients spent 89.96% of their time at home and 82.6% achieved a Karnowsky Index of 70 (generally self-caring or greater). CONCLUSIONS: HPN can be practised at non-specialist District General Hospital level achieving complication rates comparable to large specialist centres, and this lends weight to the argument for a network model to widen provision beyond large tertiary referral specialist centres in the United Kingdom.

Herpes simplex type 1 hepatitis in renal transplantation.

Herpes simplex is a rare but usually fatal cause of acute hepatitis in adults. Most previously reported cases have occurred in debilitated or immunosuppressed patients. We report two additional fatal cases that occurred in renal transplant recipients. In case 1, there is evidence that the allograft may have been the initial nidus of infection. In case 2, dissemination from a genital infection occurred and failed to respond to vidarabine therapy that was started early in the clinical course. We also review the literature concerning previously reported cases of herpes hepatitis.

Major role for arterial disease in morbidity and mortality after kidney transplantation in diabetic recipients.

OBJECTIVE: To identify clinical characteristics of diabetic end-stage renal disease patients that place individual transplant candidates at high risk for arterial morbidity and mortality after transplantation. RESEARCH DESIGN AND METHODS: We studied the course of 101 sequential renal allograft recipients with insulin-dependent diabetes mellitus, transplanted between 10 November 1980 and 1 April 1986. Arterial disorders were tabulated from medical records and interviews with individual patients, their families, and their private physicians. Documentation of discrete arterial events included recorded physical examinations, radiographic studies, laboratory data, electrocardiograms, peripheral vascular flow studies, and operative reports. The prevalence of preoperative arterial disease was compared with the occurrence of new arterial events after kidney transplantation. RESULTS: Within a mean follow-up period of 47 mo, a 30% absolute mortality rate was observed. Of these deaths, 57% resulted from arterial disorders. Clinical manifestations of arterial disease were recognized in 41% of recipients before transplantation, and 78% of these patients suffered new vascular events after transplantation. Of the entire sample, 57% developed at least one new complication of arterial disease after transplantation, whereas only 34% had no vascular diagnosis before or after transplantation. Cerebral, coronary, and peripheral arterial complications after transplantation occurred in 14, 28, and 36% of the patients, respectively. The corresponding incidences of stroke, myocardial infarction, and amputation were 12, 14, and 25%. Pretransplant coronary artery disease predisposed to new coronary events after transplantation, but only peripheral arterial complications occurred more often after transplantation compared with the preoperative period. The probability of arterial complications or death correlated with patient age at first transplant and duration of diabetes but not with sex or smoking history. CONCLUSIONS: Intrinsic arterial disease in diabetic renal allograft recipients contributes heavily to the long-term morbidity and mortality after transplantation and poses the major threat to survival. Diabetic transplant candidates greater than 35 yr of age or with clinical evidence of arterial disease should undergo an extensive vascular assessment, including stress thallium myocardial imaging and/or coronary arteriography. Such recipients should receive careful preoperative counseling about their excess risk for subsequent arterial disorders.

Successful cadaver kidney transplantation in patients highly sensitized by blood transfusions. Unimportance of the most reactive serum in the pretransplant crossmatch.

Six patients who underwent a prospective blood transfusion protocol developed antibodies reactive with 41-95% of a lymphocyte panel. These antibodies disappeared 9-18 months later, and all six patients were successfully transplanted with cadaver kidneys in spite of positive crossmatches with donor T and B cells using their most reactive noncurrent sera. Crossmatches with their current sera were negative. No patient underwent plasmapheresis, blood transfusions, or immunosuppression between the time of maximum panel reactivity and transplantation. Graft survival was 100% after a mean of 22.3 months, and the mean serum creatinine level was 2.1 mg/dl one year after grafting. A positive anti-donor T or warm B cell crossmatch with the most reactive serum may be disregarded if the most recent serum is crossmatch-negative with a cadaver kidney transplant donor.

A randomized study of intravenous fluid replacement following living-donor renal transplantation.

Fourteen adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution were randomly assigned to receive either high fluid replacement (total volume of urine output + 30 ml/hr) or low fluid replacement (constant 125 ml/hr) during the first 48 hr after grafting. High replacement recipients had significantly higher fluid intake and urine output than did low replacement recipients. However, net fluid balance at the end of the 48-hr study period was positive for both groups and not significantly different. Fractional excretion of sodium was directly related to urine output in all patients. Serum osmolality, serum sodium concentration, and urine sodium concentration were not significantly different in the treatment groups. Urine osmolality was significantly higher in the low-replacement group at 24 and 36 hr after transplantation. The i.v. replacement of total urinary output is unnecessary in adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution because such grafts can conserve sodium and water immediately after transplantation.

The hemodynamic effects of intraoperative injection of muromonab CD3.

During anesthesia 5 mg of muromonab CD3 (OKT3), an anti-CD3 monoclonal antibody, was administered prophylactically to twelve patients undergoing cadaveric renal transplantation. Preoperatively, all patients were at or near their dry body weights. Methylprednisolone 500 mg on call to or in the operating room, azathioprine 2 mg kg-1 and diphenhydramine 50 mg were administered intraoperatively to reduce the probability and severity of reported effects of OKT3. After induction of anesthesia, the patients were monitored for changes in cardiovascular variables for up to 120 min after OKT3 administration. All patients had uneventful anesthetic courses. Analysis of variance showed no significant changes from pre-OKT3 administration in heart rate, mean blood pressure, mean pulmonary artery pressure, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVRI). CVP values were a reliable indicator of PCWP with the correlation coefficient of CVP to PCWP or r = 0.78 (P < 0.00005) and PCWP = .89 x CVP + 3.78. Cardiac index (CI) increased 22% at 105 min (P < 0.05). Systemic vascular resistance index (SVRI) decreased 21% at 105 min (P < 0.05). SVRI was increased 16% at 10 min post-OKT3 (P < 0.05). All of these statistically significant values were within acceptable clinical limits. Euvolemic cadaveric renal transplant recipients receiving prophylactic steroids and diphenhydramine may receive OKT3 in the operating room for induction immunosuppression without any appreciable risk of cardiovascular compromise.

Significance of delayed graft function in cyclosporine-treated recipients of cadaver kidney transplants.

Many transplant teams are reluctant to initiate cyclosporine immunosuppression in recipients of cadaver kidney grafts with delayed graft function (DGF). The renal function of cadaver kidney grafts in cyclosporine-treated recipients was compared in 47 recipients with DGF and 57 without DGF. Regardless of initial renal function, all recipients received prednisone, azathioprine, and oral cyclosporine 5 mg/kg/day or its intravenous equivalent. All kidneys were flushed with ice-cold intracellular electrolyte solution and cold-stored for 15-54 hr (mean of 31 hr) prior to transplantation at our hospital between April 10, 1985 and November 30, 1986. Rejection crises were treated with high-dose steroids or OKT3. Cyclosporine was discontinued during courses of OKT3. Recipients with DGF had significantly higher one-month serum creatinine nadirs (2.6 +/- 1.8 mg/dl vs. 1.5 +/- 0.5 mg/dl). Actuarial graft survivals were not significantly different at one year (82.2 +/- 5.5% vs. 82.6 +/- 6.4%, all graft losses included). Mean serum creatinine levels at six months and twelve months after grafting were not significantly different (1.7 +/- 0.4 mg/dl vs. 1.8 +/- 1.2 mg/dl and 2.0 +/- 0.5 vs. 1.7 +/- 0.7 mg/dl, respectively). Delayed graft function following cadaver kidney transplantation does not adversely affect intermediate term function of kidney grafts flushed with intracellular electrolyte solution and cold-stored until transplantation when a low-dose cyclosporine induction protocol is used and cyclosporine is discontinued during OKT3 administration.

Human kidney preservation by intracellular electrolyte flush followed by cold storage for over 24 hours.

Many transplant teams are reluctant to accept kidneys preserved with intracellular electrolyte flushing followed by simple cold storage when preservation time exceeds 24 hr. This study from one center is a comparison of 63 primary cadaver kidney grafts preserved with Collins 2 solution flush followed by cold storage for 9 to 23 1/2 hr to 42 primary cadaver kidney grafts preserved by the same method for 24 to 44 1/2 hr. Kidneys cold-stored for over 24 hr had a significantly increased requirement for dialysis in the first week following transplantation (55% versus 30%). One-month serum creatinine nadirs and actuarial graft survivals were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) 2 to 9 hr prior to kidney removal reduced the requirement for first-week hemodialysis in the kidneys cold-stored for over 24 hr (23% versus 69%, P under 0.05). A human kidney preserved by the same method and cold-stored for 61 hr was successfully transplanted into a 38-year-old myelodysplastic. Satisfactory human kidney preservation can occur with intracellular electrolyte flush solutions followed by cold storage for over 24 hr when the warm ischemia time is very short.

Renal transplantation across the ABO barrier using A2 kidneys.

BACKGROUND: The waiting list for cadaveric kidney transplantation has continued to grow, and with the relative scarcity of cadaver donors, the median waiting time for patients in the United States increased to 824 days in 1994. The median waiting times for patients with blood groups B or O were 1329 and 1007 days, respectively. Allocation of blood group A2 kidneys (20% of group A) to blood group O and B patients expands their potential donor pool and shortens their waiting time for a kidney transplantation. METHODS: Between May 1991 and June 1998, we transplanted 15 A2 kidneys into 6 blood group O and 9 blood group B patients. Anti-A isoagglutinins were measured before transplantation, and patients with anti-A1 titers > or = 1:8 underwent plasmapheresis (PP). RESULTS: One patient with high titer anti-A antibodies, who did not receive PP, lost her allograft because of hyperacute rejection. Allograft function was excellent in the remaining 14 patients, with a mean serum creatinine level of 1.7 (+/-0.89) mg/dl at 1 month and 1.3 (+/-0.34) mg/dl at 1 year. The actuarial 1-year graft survival rate was 93.3+/-6.4% and the patient survival rate was 100%. CONCLUSION: We conclude that the allocation of blood group A2 kidneys for blood group O and B recipients is a practical way to expand the donor pool for these transplant candidates. PP may be important for reducing the levels of anti-A1 and anti-A2 antibodies and for reducing the risk of hyperacute rejection. Splenectomy seems to be unnecessary.

Effectiveness of a second course of OKT3 monoclonal anti-T cell antibody for treatment of renal allograft rejection.

A second course of OKT3 monoclonal anti-T cell antibody was given to 21 recipients of kidney transplants. Rejections reversed in 43% of patients in whom 95% of rejections had reversed with their initial OKT3 course. Reversal was highly dependent upon the timing of rejection, anti-OKT3 antibody production, and T cell CD3 modulation. Rejections treated greater than 90 days after transplantation were resistant to OKT3 reversal. High-titer anti-OKT3 antibodies prevented OKT3 reversal of rejection, and effective CD3 (the cell surface target of OKT3) modulation was necessary for successful OKT3 reversal of rejection. Reexposure to OKT3 further stimulated anti-OKT3 antibody production and broadened the specificity of the antibodies produced. OKT3 can effectively and safely be used a second time for treatment of early T cell-mediated renal allograft rejections if high-titer anti-OKT3 antibodies have not been made.

Fate of renal allografts transplanted in patients with urinary diversion.

Fifty-five kidneys were transplanted into 50 patients with supravesical urinary diversion at 16 transplant centers between 1970 and 1991. Of the 32 males and 18 females, 40 were adults (> or = 18 years) and 10 were less than 18 years old at the time of first transplant. Mean follow-up was 7.8 years. At last follow-up, 94% of recipients were alive and 73% of the kidneys were functioning. Fifteen kidneys were lost: 9 to rejection, 3 to noncompliance, and 3 patients died with a functioning kidney. Ten (18%) transplants were followed by surgical complications. Twenty-four (44%) were followed by medical complications of which urinary tract infection was most common. Recipients age 18 or younger had more urinary tract infections than older patients. No patient had urinary stones and no patient required medical treatment for metabolic abnormalities. We conclude that drainage of kidney transplants into a supravesical urinary diversion is an effective treatment for end-stage renal disease patients without adequate urinary bladders.

Phase I trial of HuM291, a humanized anti-CD3 antibody, in patients receiving renal allografts from living donors.

BACKGROUND: HuM291 is a humanized anti-CD3 monoclonal antibody engineered to reduce binding to Fcgamma receptors and complement fixation. HuM291 has a long serum half-life and mediated profound depletion of circulating T cells in chimpanzees; HuM291 also has significantly less mitogenic and cytokine-releasing activity than OKT3 in vitro. METHODS: A phase I dose-escalation study was conducted in 15 end-stage renal disease patients scheduled for renal allografts from living donors. Patients received one i.v. HuM291 injection before transplantation. Five doses were tested: 0.015 microg/kg, 0.15 microg/kg, 0.0015 mg/kg, 0.0045 mg/kg, and 0.015 mg/kg. Patients were followed for adverse events, laboratory abnormalities, serum cytokine levels, pharmacokinetics, and CD2+, CD3+, CD4+, and CD8+ T cell counts. RESULTS: HuM291 was well tolerated; most adverse events were mild to moderate in severity and included headache, nausea, chills, and fever. These occurred within the first few hours after HuM291 administration, resolved within 24 to 48 hr, and were likely related to cytokine release. In general, peak tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels were detected 1 to 6 hr postdosing only at the three highest doses and were generally undetectable by 24-hr postdosing. Serious adverse events possibly related to HuM291 included clotting of a fistula (two patients), chemical cellulitis (one patient), and increased serum creatinine/decreased hematocrit (one patient). At doses > or = 0.0015 mg/kg (0.1 mg/70 kg), HuM291 induced rapid, marked depletion of peripheral T cells within 2 hr; duration of T cell depletion was dose dependent. At the two highest dose levels, T cells remained depleted for approximately 1 week. CONCLUSIONS: A single HuM291 dose rapidly depleted circulating T cells in a dose-dependent manner and was associated with only mild to moderate symptoms of cytokine release.