Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

The EQUAL study: a European study in chronic kidney disease stage 4 patients.

The timing of the start of dialysis in elderly patients is driven by the desire to optimize the quantity and quality of life. Limited data exist on how the level of renal function, and uraemic signs and symptoms can be used to determine when dialysis should be initiated in elderly patients. EQUAL, an international prospective cohort study, aims to address these issues. To this end, it will enroll 3500 patients >65 years of age with CKD of various aetiologies under the care of nephrologists. These patients will be followed until death, discharge from the nephrology clinic to primary care or until the end of the observation period after 4 years of follow-up. At the time of enrollment, patients must have an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m(2) or lower, but should not yet be on dialysis. Standardized data collection will include demographics, lifestyle, comorbidities, uraemic signs and symptoms, nutritional status, medication and routine blood and urine biochemistry. It will also comprise quality of life data, information on decision making including patients preferences and patients satisfaction.

Waist circumference modifies the relationship between the adipose tissue cytokines leptin and adiponectin and all-cause and cardiovascular mortality in haemodialysis patients.

BACKGROUND: the relationships between the adipose tissue cytokines leptin and adiponectin (ADPN) and clinical outcomes have not been well studied in haemodialysis (HD) patients and remain highly controversial. As central obesity is an important modifier of the effect of various risk factors for clinical outcomes, we tested the hypothesis that waist circumference (WC) modifies the link between these cytokines and both overall and cardiovascular death in HD patients. METHODS: a total of 537 HD patients participated in a prospective cohort study. RESULTS: leptin and ADPN were inversely related to each other and robustly associated with WC (P < 0.001). During follow-up (average 29 months, range 1-47 months) 182 patients died, including 115 from cardiovascular causes. In analyses adjusting for potential confounders, there were strong interactions between leptin and WC in relationship to both all-cause (P < 0.001) and cardiovascular death (P = 0.002). Accordingly, a fixed excess of leptin signalled a gradually increasing risk for all-cause and cardiovascular mortality in patients with a large WC but an opposite effect in those with a relatively small WC. An interaction between ADPN and WC for all-cause (P = 0.01) and cardiovascular mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway leading to adverse clinical events in HD patients. CONCLUSIONS: the predictive value of leptin and ADPN for all-cause and cardiovascular death in HD patients appears to be critically dependent on WC. These findings support the hypothesis that disturbances in adipokine levels are involved in adverse clinical outcomes in HD patients with abdominal obesity.

Infodemiology of renal diseases: a novel opportunity to investigate public global interest.

OBJECTIVE: The aim of this study was to investigate the global community interest about renal diseases through relative search volumes (RSVs) of Google Trends (GT). MATERIALS AND METHODS: The online interest for the search terms hematuria (H), proteinuria (P), chronic kidney disease (CKD) and dialysis (D) was measured by evaluating RSVs from 2010 to 2019. All countries listed in GT were analysed and those presenting RSVs related to all search terms were considered following geographical position. RESULTS: Mean values of RSVs for D, CKD, H and P were 80±9%, 11±2%, 17±2% and 11±1%, respectively. D is the search term most frequently typed in English-speaking countries. On the other hand, in Latin Countries, the interest for P and H was higher than D. Searching for D, CKD and H are highly correlated whilst correlation coefficients between RSVs for D, CKD, and H with P are lower. Since 2010, the interest for renal diseases maintained stable. CONCLUSIONS: GT is a reliable tool in evaluating global interest for renal diseases in different geographical areas and temporal patterns. Although infodemiology represents a method for investigating the dissemination of information at a global level, our results suggest the need for increasing general population's interest for renal diseases especially, and move from simple interest to global awareness in the view of prevention strategies.

Present and future of kidney replacement therapy in Italy: the perspective from Italian Dialysis and Transplantation Registry (IDTR).

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50 years old; however, it greatly differs between regions for patients over 75 years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50 years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70 years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transplanted patients' prevalence to 500 pmp, and a decrease of dialysis patients from 714 to 680 pmp. The proportion of patients treated with one of the three modalities strictly depends on age, with a sharp increase of haemodialysis after the age of 50. All data suggests the necessity to improve the care of middle and older age patients who experience the higher incidence of disease and mortality.

[Census 2004 of the Italian renal and dialysis units. Basilicata - Calabria - Puglia]. / Censimento 2004 dei Centri di Nefrologia e Dialisi Italiani. Basilicata - Calabria - Puglia.

The Italian Society of Nephrology (SIN) sponsored in 2004 a National Census of the Italian renal and dialysis units. This paper presents the main structural, technical, organizational features, as well as the human resources and the activities of three South-East regions of Italy: Basilicata (B), Calabria (C), and Puglia (P). EPIDEMIOLOGY: incidence of dialysis patients was 149 per million population (pmp) in B, 134 pmp in C and 172 pmp in P; prevalence of dialysis patients 729, 694 and 886 pmp, respectively; prevalence of transplanted patients 188 in B, 264 in C and 249 pmp in P; gross mortality rate of dialysis patients was 12.7% (B), 12.2% (C) and 10.8% (P). TYPE OF VASCULAR ACCESS IN PREVALENT DIALYSIS PATIENTS: arteriovenous fistula: 83.9% (B), 87.7% (C) and 86.5% (P); central venous catheter: 14.2% (B), 8.4% (C) and 11.2% (P); vascular graft 1.9% (B), 3.9% (C) and 2.3% (P). STRUCTURAL RESOURCES: nephrological beds 37, 34 and 88 pmp, respectively; dialysis stations 265, 209 and 207 pmp. PERSONNEL RESOURCES: renal physicians 45 (B), 67 (C) and 64(P) pmp; renal nurses 189, 190 and 207 pmp; each nephrologist cares for 16 (B), 10 (C) and 14 (P) dialysis patients, whereas each renal nurse takes care of 3.8 (B), 3.7 (C) and 4.3 (P) dialysis patients. ACTIVITY: hospitalizations 1378, 1834 and 3439 pmp, respectively; renal biopsies 40 (B), 64 (C) and 107 (P) pmp. The main goal of this project was to create a reference for benchmarking studies. Therefore, data from the Puglia region were compared to data from other regions with similar population size (such as Piemonte and Emilia-Romagna). Moreover, a Census may became a useful qualitative tool for renal registries: this report compares data from the Census with data collected by the dialysis and transplantation registry of the Puglia region. Generally speaking, prevalence for Basilicata and Calabria is close to the Italian one, whereas incidence is inferior; things are opposite in Puglia. Furthermore, compared to Basilicata, Calabria and Italy on average, the Puglia region shows a significant higher number of in-patient beds and a lower DRG weight. Compared to Piemonte, Emilia Romagna and Italy on average, all the three South-East regions do not show differences in number/pmp of dialysis centres. More physicians (nephrologists = 80%) are reported to be active in Puglia and Calabria, compared to Piemonte and Emilia Romagna. Nurses in Puglia look after a greater number of dialysis patients than in Calabria and Basilicata. The number of renal biopsies/ pmp is similar to the Italian mean only in Puglia; it is inferior in the other two regions. These data highlight many differences among these three South-East regions, as well as among Piemonte, Emilia Romagna and Puglia. A relevant inequality in health care structures and resources has been found and discussed.

Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia.

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.

Prognostic relevance of the expression of Tdt and CD7 in 335 cases of acute myeloid leukemia.

We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 102 of 332 (30%) evaluable cases; 37 of 93 assessable (40%) CD7+ patients attained a CR as compared to 114/204 (56%) CD7- (P = 0.013). Duration of survival was significantly shorter for patients with CD7+ or Tdt+ AML (P = 0.006 and 0.001, respectively). In a multivariate analysis, Tdt was found to significantly adverse achievement of CR (P = 0.018), while CD7 affected duration of CR (P = 0.037). Overall the expression of either Tdt or CD7 correlated with a relatively high expression of CD34 (P < 0.001), GP-170 (P = 0.003), lymphoid antigens (LyAg) (P < 0.001), t(9;22) or anomalies of chromosome 5/7 (P < 0.001). Finally, we pooled the patients into four phenotypic classes, according to the presence of Tdt, CD7 or both: [Tdt-CD7-], [Tdt+CD7-], [Tdt-CD7+] and [Tdt+CD7+]. The category [Tdt+CD7+] was characterized by a more unfavorable outcome as suggested by a lower rate of CR (P < 0.001) and a shorter duration of survival as compared to cases [Tdt-CD7-], [Tdt+CD7-] and [Tdt-CD7+] (P = 0.002). This figure is consistent with the frequent convergence in the subset [Tdt+CD7+] of GP-170 positivity (P = 0.003), translocation t(9;22), anomalies of chromosome 5 and/or 7 (P < 0.001) and signs of lineage infidelity (deviant expression of lymphoid antigens) (P < 0.001). We conclude that the expression of Tdt or CD7 is associated with an unfavorable outcome and that the combination of both defines a clinical subset with a poorer prognosis due to the significantly higher association with MDR phenotype, and 'poor prognostic' chromosomal abnormalities.

[Standardization criteria to ensure the uniformity of data collection by the Italian Registry of Dialysis and Transplantation]. / Criteri di uniformità per la raccolta dei dati del Registro Italiano di Dialisi e Trapianto.

The Italian Registry of Dialysis and Transplantation (RIDT) collects data concerning patients in renal replacement therapy (RRT) sent from Regional Registries. Until 2003, the data were sent in summary tables. From 2004, each region has been sending patient data as single non-summarized forms (i.e. one record for each patient). This paper summarizes the collection criteria and the ideal method to codify data ensuring that data sent to the RIDT are consistent. This standardization process is necessary to ensure the statistical analyzability of the data and their comparability with data from other registries. Moreover, the standardization process is the initial step in allowing the RIDT to obtain clinical data to transform the registry from an epidemiological registry to a clinical governance instrument.

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.

Influence of extracellular volume expansion on circulating PTH1-84 in subjects with mild essential hypertension.

The effect of acute volume expansion by saline (1 L/40 min) on serum parathyroid hormone (PTH) concentration was studied in 28 subjects with mild essential hypertension. At the zenith volume expansion there was a significant increase in systolic pressure (7 +/- 2 mm Hg, P < .01) while diastolic pressure and heart rate showed minor (NS) variations. The rise in systolic pressure was accompanied by a significant (P = .02) decrease in plasma ionized calcium (from 1.12 +/- 0.03 to 1.08 +/- 0.03 mmol/L) and by a marked PTH increase (from 36 +/- 3 to 60 +/- 4 pg/mL, P < .01). The arterial pressure variations were independent of changes in serum PTH. In a second experiment (n = 11), aimed at preventing the changes in calcium concentration brought about by hemodilution, we infused the same volume of saline with the addition of 1.25 mmol of elemental calcium. In this study PTH showed a small, nonsignificant, decrease while systolic pressure changes were similar to those of the first study (ie, an isolated 9 +/- 4 mm Hg increase in systolic pressure). In a third experiment (n = 7), aimed at studying the effect of raised plasma PTH concentration in isocalcemic conditions, PTH1-38 was continuously infused (1 ng/kg/min) during the volume expansion phase performed with the same solution as used in the second experiment. The hemodynamic changes were again identical to those of the other studies (an isolated 9 +/- 3 mm Hg increase in systolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperfiltration and calcium metabolism in essential hypertension.

To test the hypothesis that hyperfiltration in essential hypertension is linked to alterations in calcium metabolism, we studied the relationship between urinary calcium excretion and glomerular filtration rate (GFR, creatinine clearance) in 38 untreated essential hypertensives on a free diet. We also studied the influence of changes in calcium intake on GFR in 30 essential hypertensives (15 with well-defined hypercalciuria and 15 with normal urinary calcium excretion) and in 11 normotensive healthy subjects. In the patients on a free diet, urinary calcium excretion was directly and independently related to GFR (r = 0.56, P less than .001), while serum calcium showed an opposite trend (r = -0.27, P = .12). In patients on fixed calcium diets, GFR was significantly higher (P = .008) at low calcium intake (115 +/- 31 mL/min/1.73 m2) than at high calcium intake (98 +/- 22 mL/min/1.73 m2). Further analysis showed that the hyperfiltering effect of low calcium almost exclusively occurred in hypercalciuric patients and in hypertensive women. In hypercalciuric hypertensives there was a highly significant inverse correlation between GFR and serum calcium (r = -0.51, P = .004) and a similar correlation between GFR and plasma renin activity (r = -0.70, P = .003) in the high calcium phase of the study. Changes in calcium intake had no influence on GFR in normal subjects (Low Ca 103 +/- 22 mL/min/1.73 M2, High Ca 110 +/- 23 mL/min/1.73 m2). The data indicate that alterations in calcium metabolism interfere to an important extent with mechanism(s) regulating GFR in essential hypertension.

[Prevalence of insulin-dependent and non-insulin-dependent diabetes among Italian patients on replacement therapy. Preliminary survey at 3 dialysis centers]. / Prevalenza del diabete insulino e non insulino-dipendente nei pazienti Italiani in terapia sostitutiva. Indagine preliminare su tre Centri Dialisi.

We carried out a retrospective survey to assess prevalence and type of diabetes in three Italian Renal Units located respectively in the North (Tradate, Varese), in the Middle (Latina) and in the South (Reggio Calabria) of Italy. The prevalence of diabetes among patients accepted for RRT was 10.5% (60/659). 40 patients (66.7%) were non-insulin dependent and only 6 patients were insulin-dependent. A similar pattern was observed among the 289 patients referred to the Renal Unit of Reggio Calabria during 1972-1987 for evaluation of Chronic Renal Failure. Our data suggest that among the Italian diabetic patients treated by dialysis and transplantation insulin-dependent diabetes is uncommon. This finding could be explained by the low incidence of insulin-dependent diabetes in Italy.

[Xerostomia and Xerophthalmia in haemodialysis patients]. / Xerostomia e Xeroftalmia nei pazienti in dialisi.

BACKGROUND: A reduction in salivary and lachrymal secretion has been described in many pathologies; however, such alterations have not been described in patients with renal failure. This study was designed to estimate the frequency of alterations in salivary and lachrymal secretion in haemodialysed patients. PATIENTS ABD METHODS: We studied 63 haemodialysed patients and 23 healthy control subjects. In all of them we tested salivary secretion (Saxon test), lachrymal secretion (Shirmer test) as well as the presence of symptoms of xerostomia and xerophthalmia. In a subgroup of patients We investigated any evidence of ocular lesions and tissue damage of salivary glands (histopathology). We also tested the correlation between salivary and lachrymal secretion and autonomic nervous system function. Furthermore, we also studied the association between xerostomia and xerophthalmia and serum auto antibodies (anti nuclear, anti-Ro (SS-A), anti-La (SS-B)) and anti HCV antibodies. RESULTS: On average salivary and the lachrymal secretion was markedly reduced in uraemic patients compared with healthy controls. We found the alterations in salivary glands function to be strongly related to salivary glands fibrosis and atrophy and independent of amyloid accumulation. On the other hand, we observed that xerostomia and xerophthalmia were unrelated to autonomic dysfunction as well as to HCV infection and circulating auto antibodies. Moreover, xerophthalmia was frequently associated with evidence of corneal damage. CONCLUSIONS: Reduced salivary and lachrymal secretion is frequent in uraemic patients. Such alterations are often asymptomatic and could be an expression of the accelerated age-dependent decline in glandular function and the attendant fibrosis and atrophy.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

[Deposits with anti-globulin activity in dermatitis herpetiformis]. / Depositi con attività antiglobulinica nella dermatite erpetiforme.

Skin biopsy specimens from 2 patients with dermatitis herpetiformis were examined by means of direct immunofluorescence with fluoresceinated aggregated human IgG (FAIgG) for the presence of tissue antiglobulin activity. Positive FAIgG staining was seen in both skin biopsy specimens yielding a fluorescence pattern similar to that of immunoglobulin and complement deposits. Tissue antiglobulin activity was no more detectable in a second skin biopsy obtained from one patient whose rash was controlled by Dapsone. These findings suggest an involvement of tissue antiglobulin activity in the pathogenesis of dermatitis herpetiformis. In fact, tissue antiglobulin activity is capable of acting as an immunoabsorbent and binding immunocomplexes from the circulation.

Influence of ANF on the cardiovascular response to volume expansion in haemodialysis patients.

Plasma ANF concentration in uraemic patients is very sensitive to changes in extracellular volume. It is unknown, however, if the release of this vasoactive hormone has a compensatory role in the haemodynamic response to extracellular volume expansion in these patients. We investigated the effect of isolated ultrafiltration followed by isovolumic re-expansion by saline in seven haemodialysis patients. The experiment was repeated on two occasions and the UF rate as well as the rate of volume re-expansion in the two studies were accurately matched. During the phase of volume re-expansion, we infused either ANF (0.83 microgram/min) or a placebo, in random order and cross-over. Central venous pressure, arterial pressure, haematocrit, and plasma ANF concentration were measured in baseline conditions, after ultrafiltration, and 0, 15, and 30 min after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltration caused a marked reduction in central venous pressure and in arterial pressure and a pronounced haematocrit increase. These changes were reversed by volume re-expansion. In the active experiment, during the phase of volume re-expansion ANF infusion doubled plasma ANF concentration as compared to control experiment but it did not affect the ongoing haemodynamic response nor the haematocrit changes. Doubling of plasma ANF concentration has no influence on the haemodynamic and microcirculatory adaptations to acute volume expansion in haemodialysis patients. The data indicate that it is unlikely that raised plasma ANF concentration has a major role in the cardiovascular response to acute extracellular volume expansion in these patients.