Exploring suicidal behaviours by probation clients-a qualitative near-lethal study.

Background: Existing research emphasizes that offenders serving community based sentences are at an increased risk of suicide compared with the general population, however, there is little understanding about the causes of this risk. The aim of the current research was to understand how to support probation clients and prevent suicide, by exploring the experiences of probation clients who carried out near-lethal suicide attempts whilst under probation supervision. Methods: In-depth interviews were carried out with seven probation clients who made near-lethal suicide attempts whilst serving a probation sentence. Data were analysed using Interpretative Phenomenological Analysis. Results: Participants recounted negative experiences which they perceived to be linked to their suicidal feelings and behaviours, such as experiencing bereavements, perceived loss of control over their mental state or situation, and difficulties relating to stages of their probation sentence. Participants expressed severe difficulties with trusting authorities, making disclosure of suicidal feelings problematic. However, participants emphasized the role that purposeful and meaningful activity can play in suicide prevention. Conclusions: Suicide prevention strategies must be tailored to the needs of probation clients across the UK. Mandatory training for probation staff is recommended to help reduce suicides, and support from external agencies should be sought where possible.

Do mesangial immune complex deposits affect the renal prognosis in membranous glomerulonephritis?

Patients with rheumatoid arthritis who develop membranous glomerulonephritis associated with gold or penicillamine therapy have been shown to get better when the drugs are discontinued, whereas up to 50% of patients with idiopathic membranous glomerulonephritis develop renal failure. A feature of the lesion in rheumatoid disease is the presence of mesangial immune complex deposits in addition to the basement membrane deposits of classical idiopathic membranous glomerulonephritis. To determine whether the presence of mesangial immune complexes indicates a different renal outcome in membranous glomerulonephritis we studied 3 groups: group A 10 patients with rheumatoid arthritis and drug induced membranous glomerulonephritis with mesangial immune complex deposits, group B 14 patients with idiopathic membranous glomerulonephritis with additional mesangial immune complex deposits and group C 25 patients having classic idiopathic membranous glomerulonephritis with deposits solely in the glomerular basement membrane. After median follow up of 72 months, nephrotic range proteinuria resolved in all cases in group A after drug withdrawal, 93% of group B, but only 60% of group C (groups A + B vs C, X2 = 7.8, p < 0.01). Serum creatinine remains less than 500 mumol/l in all patients in group A, 93% of group B, but only 64% of group C (groups A + B vs C, X2 = 7.6, p < 0.01). Mesangial immune complex deposits were predominantly of the IgM isotype in both the rheumatoid and idiopathic membranous group. The presence of mesangial immune complex deposits suggests either a different pathogenesis or host responsiveness to that found in classic idiopathic membranous glomerulonephritis, and predicts a more favourable renal outcome.

Treatment of hypercalcaemia with pamidronate in patients with end stage renal failure.

Pamidronate was given to 10 patients with end stage renal failure who had become symptomatically hypercalcaemic due to the use of calcium based phosphate binders and alphacalcidol. All patients were initially treated with rehydration, increased dialysis and withdrawal of drugs, however despite this they remained symptomatic and the serum calcium remained elevated, mean 3.89 mmol/l (range 3.44-4.74). Pamidronate was given, and the serum calcium had declined to 2.92 mmol/l (2.79-3.84), p < 0.01 by the third day. The reduction in serum calcium observed with pamidronate was more rapid than that in 9 patients who developed asymptomatic hypercalcaemia, mean serum calcium 3.45 mmol/l (3.4-3.56), with an actual median reduction of 0.72 mmol/l (0.37-1.30) in the pamidronate group after 3 days compared to 0.20 mmol/l (0.10-0.52) in the conservatively treated asymptomatic group, p < 0.01, and a median percentage decrease of 19% (10-30) in the pamidronate group and 6% (3-15) in the asymptomatic group, p < 0.01. In this study pamidronate was a safe and effective agent in reducing serum calcium in a group of hypercalcaemic dialysis patients.

Thyroid hormone levels in acute renal failure.

We investigated the plasma concentrations of thyroid hormones in 27 patients with acute renal failure. Both the mean free T3, 1.17 +/- 0.74(SD) pmol/L (range 0.5-2.9 pmol/L) and total T3 plasma concentrations, 0.43 +/- 0.14 nmol/L (range 0.3-0.7 nmol/L) were reduced compared to the normal range (3.3-8.2 pmol/L and 1.0-3.0 nmol/L, respectively). In all 15 patients with plasma creatinine > 3.33 mg/dL (295 mumol/L), the mean FT3 was 0.92 pmol/L and the plasma concentrations have all been < 1.5 pmol/L. There was a weak correlation between the plasma creatinine and the plasma concentrations of TT3 (r = 0.38, p = 0.049). Similarly, both plasma free T4 and total T4 were also reduced in the patients compared to the normal range: mean free T4 5.91 +/- 3.68 pmol/L, range 1.0-13.1 pmol/L, and total T4 47.80 +/- 29.31 nmol/L, range 5-99 nmol/L; normal range 9.4-25.0 pmol/L and 50-160 nmol/L, respectively. There was no difference between the ranges in either plasma TSH, patients 1.19 +/- 1.25 mU/L, range 0.1-4.9 mU/L, vs. control range 0.3-6.0 mU/L; and TBG, patients 19.05 mg/L +/- 3.69, range 11.0-26.9 mg/L, controls range 13.0-30.0 mg/L. Thus we have determined that patients in the early phase of ARF have consistently reduced plasma concentrations of both free and total T3, and reduced concentrations of free and total T4; and that the reduction of TT3 is dependent upon the plasma creatinine level.

Neurotoxicity of acyclovir in patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis.

We report two cases of herpes-zoster in which the administration of acyclovir to patients with end-stage renal failure treated by continuous ambulatory peritoneal dialysis (CAPD) resulted in acyclovir neurotoxicity, even though the doses administered were within those recommended by the manufacturer's data sheet for patients with renal failure. Acyclovir removal was negligible with peritoneal dialysis and one patient died. The other patient was successfully treated with hemodialysis, which effectively reduced plasma concentrations, resulting in an improvement in conscious state. Acyclovir neurotoxicity should be considered in patients with renal failure who have been treated for viral infections, in whom the conscious state has deteriorated despite normal brain computed tomography (CT) scan and lumbar puncture investigations. Hemodialysis is the preferred treatment for the rapid removal of acyclovir.

A peptide family being re-united: the angiotensins coming in from the cold.

The renin-angiotensin-aldosterone system is now considered to be far more complex than previously thought when the vasoconstrictor and other physiological effects of the octapeptide angiotensin II in the circulating blood were emphasized. The reasons for this altered viewpoint, involving angiotensins other than the octapeptide in the regulation of blood pressure, water and electrolyte homeostasis, are briefly advanced and discussed.

C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.

Audit of the use of calcium carbonate as a phosphate binder in 100 patients treated with continuous ambulatory peritoneal dialysis.

We studied the effect of converting 100 established CAPD patients from aluminium- to calcium-based phosphate binders. After a follow-up of 1 year only 60% of patients remained on calcium carbonate. Hypercalcaemia was the major problem, with more than 40% of patients having a serum calcium in excess of 3.0 mmol/l. Several patients required hospitalization for symptomatic hypercalcaemia. Hypercalcaemia was more common in patients with normal serum parathyroid hormone concentrations (65 versus 25%, P less than 0.01). Serum phosphate control was better prior to commencing calcium carbonate when patients were treated with aluminium phosphate binders mean 1.71 +/- 0.15 mmol/l (SEM) than at the time of maximum serum calcium concentration, 1.81 +/- 0.25, P less than 0.05. This study does not confirm the findings of others, which have suggested that calcium carbonate is a safe and effective phosphate binder for patients with end-stage renal failure.

An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy.

Urinary excretion of tissue kallikrein is reduced in essential hypertension. Although a similar finding has been reported in spontaneously hypertensive rats (SHR), only a few studies have been concerned with the amount of enzyme within the kidney both at the time of onset and during progression of the hypertension. We have performed an ontogenic study on the renal parenchymal values and immunoreactivity of tissue kallikrein in Okamoto SHR aged 4-78 weeks. Additionally, these two parameters were analysed in human biopsies taken from patients with hypertensive nephropathy. The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure. In contrast, 78 weeks SHR and human biopsy tissue showed a substantial reduction in tissue kallikrein values. Also, both renal tissues showed a reduction in immunoreactivity in the cells of the connecting tubules that specifically store the enzyme. In advanced hypertension the observed reduction in tissue kallikrein was probably secondary to a loss of distal tubular mass, as a result of tubular atrophy and fibrosis. The greater values for renal tissue kallikrein in the kidney and reported reduced urinary excretion during the early phases of spontaneous hypertension may be explained by a primary defect in the mechanisms that regulate release of tissue kallikrein from the connecting tubule cells.

Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow.

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.

Pulmonary response to toner upon chronic inhalation exposure in rats.

A chronic inhalation study of a test toner was conducted by exposure of groups of F-344 rats for 6 hr/day, 5 days/week for 24 months. The test toner was a special Xerox 9000 type xerographic toner, enriched in respirable-sized particles compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The target test aerosol exposure concentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high) mg/m3. Titanium dioxide (5 mg/m3) and crystalline silicon dioxide (1 mg/m3), used as negative and positive controls for fibrogenicity, were also evaluated. Inhalation of the test toner or the control materials showed no signs of overt toxicity. Body weight, clinical chemistry values, food consumption, and organ weights were normal in the toner- and TiO2-exposed groups, except for a 40% increase in lung weight in the toner high-exposure group. All of the changes in the toner-exposed groups were restricted to the lungs or associated lymph nodes. A chronic inflammatory response was evident from the bronchoalveolar lavage parameters for the toner high-exposure group. The incidence of primary lung tumors was comparable among the three toner-exposed groups and the TiO2-exposed, and air-only controls, as well as consistent with historical background levels. A mild to moderate degree of lung fibrosis was observed in 92% of the rats in the toner high-exposure group, and a minimal to mild degree of fibrosis was noted in 22% of the animals in the toner middle-exposure group. The pulmonary changes in the toner high-exposure group were smaller in magnitude than those found in the crystalline silica-exposed group. The comparative fibrogenic potency of TiO2, toner, and SiO2 was estimated to be 1:5:418 using a dosimetric model and assuming a common mechanistic basis. There were no pulmonary changes of any type at the toner low-exposure level, which is most relevant in regard to potential human exposures. The lung alterations in the toner high-exposure group are interpreted in terms of "lung overloading," a generic response of the respiratory system to saturation of its detoxification capacity. The maximum tolerated dose (MTD) criterion was met at the toner high (16 mg/m3)-exposure level.

Lung clearance and retention of toner, utilizing a tracer technique, during chronic inhalation exposure in rats.

Male and female F-344 rats were exposed to 6 hr/day, 5 days/week for up to 24 months to a special test toner at 0, 1, 4, and 16 mg/m3, TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3 by the inhalation route. 59Fe-labeled iron oxide and 85Sr-labeled polystyrene particles were periodically inhaled by the nose-only route and used to measure alveolar clearance rates during the course of the study. This method was used to describe a maximum functionally tolerated dose (MFTD). Pulmonary retention of toner and control materials (TiO2 and SiO2) was measured after 3, 9, 15, 21, and 24 months of exposure. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The final pulmonary burdens of toner at the three exposure levels were 0.22, 1.73, and 15.6 mg/lung, respectively. Alveolar clearance of both tracers was substantially impaired at the toner high-exposure level, and moderately slowed at the toner middle-exposure level. The excessive quantity of toner retained and the substantially retarded clearance in the toner high-exposure group are indicative of "lung overloading." Alveolar clearance of 85Sr-polystyrene particles was slightly slowed in the TiO2-exposed group and substantially impaired in the SiO2-exposed group. The alveolar clearance of the unexposed rats decreased about 30% during the study, a change ascribed to aging. For a general description of the toxicokinetics of the various dusts, a semiempirical kinetic model was developed, which could generally be useful for the extrapolation of lung retention of insoluble particles from a subchronic to a chronic inhalation study. Both the maximum tolerated dose (MTD) and the MFTD were exceeded at the toner high-exposure level during the study in rats.

Twenty years of investigating angiotensin activity: an overview.

A short account of the renin-angiotensin-aldosterone system is given with emphasis on the relationship between the octapeptide angiotensin II and its decapeptide precursor angiotensin I. Although the decapeptide is generally assumed to have no biological activity, extensive investigations have indicated that such an assumption is almost certainly unjustified. The implications of the findings are briefly outlined and discussed.

Electrolyte and humoral responses of renal transplant patients to head-out water immersion.

Eighteen renal transplant recipients and sixteen volunteers were subjected to the physiological manoeuvre of head-out water immersion, in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. Although the tubular sodium response to water immersion was normal, tubular potassium excretion was markedly different in the transplant patients. Plasma values of atrial natriuretic factor increased in both groups and showed a close temporal relationship to urinary excretion of cyclic GMP. The attenuation in transplant recipients of the well-documented suppression of plasma renin activity during water immersion was probably due to a combination of factors, namely lack of renal innervation and an increase in circulating ANF. The small but significant increase in the excretion of enzymically active urinary kallikrein observed only in the transplant recipients during immersion still requires explanation.

Cellular localisation of atrial natriuretic factor in the human kidney.

We have localised atrial natriuretic factor (ANF) in the human kidney by immunocytochemistry and radioimmunoassay. ANF is specifically visualised in the distal convoluted tubule cells and the intercalated cells of the connecting tubules and collecting ducts of the human nephron. The number of immunoreactive cells and tissue values for the peptide were compared between samples from normal kidneys and biopsies obtained from hypertensive patients, in whom the tissue ANF immunoreactivity was found to be reduced. Specific experiments are necessary to establish whether renal ANF is synthesised de novo or captured through endocytosis by the renal tubular cells. The possible functional roles of renal ANF are discussed.

Presence of immunoreactive tissue kallikrein in human polymorphonuclear (PMN) leucocytes.

The presence of tissue kallikrein in polymorphonuclear (PMN) leucocytes from normal human blood and from patients with rheumatoid arthritis and pyelonephritis was investigated. Immunoreactive tissue kallikrein was specifically detected in neutrophil leucocytes. PMN leucocytes displayed a granular staining. In the synovial membrane and kidney, the cells were aggregated into pockets as part of an inflammatory infiltrate. The presence of immunoreactive tissue kallikrein in human PMN leucocytes may provide a new insight into the importance of this enzyme in inflammation.

Natural course of penicillamine nephropathy: a long term study of 33 patients.

To elucidate the natural course of the nephropathy associated with penicillamine and thereby facilitate its clinical management 33 patients with rheumatoid arthritis who developed proteinuria during treatment with oral penicillamine were studied in detail throughout their renal illness. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 74 months (range 16-148 months). Fourteen patients developed proteinuria within six months after the start of treatment and 27 within 12 months. When treatment was stopped the proteinuria reached a median peak of 4.2 g/24 h (range 0.3-15.0 g/24 h) at one month (range 0-7 months) before resolving spontaneously by six months (12 patients), 12 months (21), or 18 months (29). In all patients but one, who developed carcinoma of the renal pelvis, proteinuria resolved by 21 months and its median duration was eight months. The median first and last measurements of creatinine clearance showed no appreciable change (80 ml/min and 78 ml/min), and no patient died from or needed treatment for renal failure. The HLA-B8 or HLA-DR3 alloantigen, or both, were identified in 10 patients. Renal biopsy specimens showed membranous glomerulonephritis in 29 patients, minimal change nephropathy in two, and electron dense deposits in the mesangial regions in two. In all the patients whose nephropathy was due solely to treatment with penicillamine the proteinuria resolved completely when the drug was withdrawn; renal function did not deteriorate, and corticosteroids were unnecessary.

The question of lung involvement in angiotensin II-induced rises in circulating plasma (K+) and arterial blood pH.

The reported patterns of raised plasma [K+] and arterial blood pH associated with intravenous infusion of angiotensin II in experimental animals are discussed with emphasis on the possible role of the lungs in these observed responses.