The naive CD4+ count in HIV-1-infected patients at time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery

Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1-infected patients. The focus was on the naive CD4 + cell time course and associations between naive CD4 + cell counts and established prognostic markers. Total and naive CD4 + cell counts were measured using flow cytometry. The HIV-RNA detection limit was 20 copies/ml. During 36 months of HAART, the total CD4 + count followed a triphasic pattern, reflecting an initial phase of rapid redistribution from lymphoid tissues, followed by a slow increase, partially due to an increase in naive CD4+ cell count. From Month 18 onwards, both naive and total CD4 + cell counts stabilized, although viral suppression was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological recovery that can be obtained from treatment. Surprisingly, the naive CD4 + cell count tended to stabilize at a subnormal level after 18 months of HAART. This finding merits further investigation.     

Lack of significant association between intima-media thickness in the carotid artery and serum TSH level. The Troms? Study.

BACKGROUND: Increased arterial wall intima-media thickness (IMT) is an early feature of atherosclerosis and has been reported to be altered in patients with thyroid dysfunction. The present study was performed to examine the relation between carotid artery intima-media thickness and possible variations in thyroid function in normal subjects using serum TSH as a surrogate index of thyroid function. DESIGN: A total of 2034 subjects (974 males) were studied, 1856 or whom were non-users of thyroxine. The subjects not taking thyroxine were classified into three groups, those with a low serum TSH (0.48 mIU/L (2.5 percentile, those with serum TSH from 0.48 to 4.16 mIU/L, and those with high serum TSH of >4.16 mIU/L (97.5 percentile). Carotid ultrasound was performed in each all 2034 subjects to determine IMT. RESULTS: Among those not taking thyroxine, subjects in the low serum TSH group had a higher mean IMT as compared to those in the normal and high serum TSH groups but the differences were not significant when adjusted for gender, age, smoking status, body mass index, systolic blood pressure and serum cholesterol (0.88 +/- 0.15 mm, 0.84 +/- 0.16 mm, and 0.84 +/- 0.24 mm respectively). Subjects taking thyroxine had significantly higher IMT than those not taking thyroxine (0.89 + 0.20 mm versus 0.84 + 0.17 mm, p<0.01). CONCLUSIONS: No significant relationship between carotid IMT and serum TSH levels was observed in normal, non thyroxine taking, subjects. Carotid IMT was increased in subjects taking thyroxine. Whether the increase in carotid IMT is due to thyroxine ingestion or underlying thyroid disease cannot be answered from the study.     

Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study)

Aims/hypothesis

The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA_1c.

Methods

This study was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n?=?986) who gave birth between 1992 and 2000. Control mothers (n?=?91,441) were women from the background population, matched according to age and year of childbirth. Age at follow-up was 32–66 years.

Results

Mortality rate was increased threefold in mothers with diabetes compared with control mothers (HR 3.41 [95% CI 2.42, 4.81]; p?<?0.0001), and was also increased with pre-gestational kidney dysfunction (normoalbuminuria, HR 2.17 [95% CI 1.28, 3.68]; microalbuminuria, HR 3.36 [95% CI 0.82, 13.8]; macroalbuminuria, HR 12.9 [95% CI 5.45, 30.7]). Moreover, the presence of hypertension prior to or at any time during pregnancy and of pre-eclampsia also increased mortality rate (hypertension, HR 4.34 [95% CI 2.13, 8.84]; pre-eclampsia, HR 5.55 [95% CI 2.71, 11.4]). Mortality rate also increased with higher levels of HbA_1c in early pregnancy (HbA_1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA_1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA_1c <64 mmol/mol (<8%) in the first trimester and normal pre-gestational urinary albumin excretion rate (n?=?517), mortality rate was comparable with that of control mothers. Among mothers with diabetes, mortality rate was associated with HbA_1c level: per 11 mmol/mol (1 percentage point) increase in HbA_1c, HR was 1.52 (95% CI 1.19, 1.94; p?=?0.001). In mothers with diabetes, the overall incidence of hospital admissions was more than double (incidence rate ratio [IRR] 2.69 [95% CI 2.59, 2.80]; p?<?0.0001) that of control mothers, as were admissions with various diagnoses from 14 out of 19 ICD-10 chapters. Among mothers with diabetes, the IRR for hospital admissions increased with the level of HbA_1c: per 11 mmol/mol (1 percentage point) increase in HbA_1c, HR was 1.07 (95% CI 1.04, 1.10; p?<?0.0001).

Conclusions/interpretation

Overall, mothers with type 1 diabetes have a two- to threefold increase in mortality and morbidity rates. HbA_1c levels, level of albuminuria around the time of conception, and the presence of hypertension and pre-eclampsia are important risk factors for mortality/morbidity in this cohort. However, it is reassuring that mothers with type 1 diabetes without kidney complications and with HbA_1c <64 mmol/mol (<8%) in early pregnancy have a similar survival potential during the period where they are raising their children to that of control mothers from the background population.

     

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre

BACKGROUND: Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. PATIENTS AND METHOD: We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10. RESULTS: There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. CONCLUSION. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.     

Granulocyte colony-stimulating factor increases CD4+ T cell counts of human immunodeficiency virus-infected patients receiving stable, highly active antiretroviral therapy: results from a randomized, placebo-controlled trial

Thirty human immunodeficiency virus (HIV)-infected patients with CD4+ T cell counts <350 cells/mm3 who had received stable, highly active antiretroviral therapy (HAART) for at least 24 weeks were randomized to receive either placebo or granulocyte colony-stimulating factor (G-CSF; 0.3 mg/mL 3 times a week) for 12 weeks. Blood samples were collected at specified time points. G-CSF treatment enhanced the total lymphocyte count (P=.002) and increased CD3+ (P=.005), CD4+ (P=.03), and CD8+ (P=.004) T cell counts as well as numbers of CD3-CD16+CD56+ NK cells (P=.001). The increases in CD4+ and CD8+ cell counts resulted from increases in CD45RO+ memory T cells and cells expressing the CD38 activation marker. Lymphocyte proliferative responses to phytohemagglutinin and Candida antigen decreased, whereas NK cell activity and plasma HIV RNA did not change during G-CSF treatment. After 24 weeks, all immune parameters had returned to baseline values. This study suggests that G-CSF treatment of HIV-infected patients receiving stable HAART increases the concentration of CD4+, CD8+, and NK cells without inducing changes in the virus load.     

Reduced urinary excretion of epidermal growth factor in incipient and overt diabetic nephropathy

To study the relationship between glomerular and tubular function we investigated glomerular filtration rate (GFR), urinary albumin excretion, and urinary excretion of epidermal growth factor (EGF, a mitogenic peptide synthesized in the renal tubular cells) in normal subjects (group I, n = 7) and in Type 1 (insulin-dependent) diabetic patients with normoalbuminuria (group II, n = 11); with incipient nephropathy (microalbuminuria) (group III, n = 9); with nephropathy and normal GFR (group IV, n = 12); and with reduced GFR (group V, n = 8). EGF (nmol 24 h-1) decreased with progressive glomerular involvement, from 7.9 (4.1-10.5) (median and range) in group I, to 6.7 (1.3-9.2) in group II, 5.0 (3.6-7.4) in group III, 4.1 (2.5-9.5) in group IV, and 1.1 (0.1-2.5) in group V. The urinary excretion of EGF was significantly reduced in patients with elevated UAE (group III, IV, and V) compared with normal control subjects (p less than 0.05). A significant correlation between urinary excretion of EGF and GFR (r = 0.71, p less than 0.001) and an inverse correlation between the urinary excretion of EGF and albumin (r = -0.35, p less than 0.05) was demonstrated in the Type 1 diabetic patients with GFR greater than 90 ml min-1. Our study demonstrates that urinary excretion of epidermal growth factor diminishes with increasing nephron impairment, and that renal tubular function as judged by the excretion of EGF is reduced early in the development of diabetic kidney disease.     

Post-craniotomy neuronavigation based purely on intraoperative ultrasound imaging without preoperative neuronavigational planning

Neuronavigation has become an established technology which provides objective data for localization in 3D space and thus decreases uncertainties regarding tumor localization, relation to vasculature, safe trajectories, and craniotomy design during surgery. We have evaluated whether neuronavigation based purely on 3D ultrasound without any preoperative navigational imaging can provide necessary information for navigation and resection control. This application is a new way of utilizing ultrasound-guided neuronavigation. Eighteen patients were operated on with ultrasound-based navigation only; they represented 16% of all the 131 navigation-assisted procedures during our 1-year study period. Of the procedures, 2 were planned as diagnostic biopsies, 1 was resection of an abscess, and 15 were tumor resections. Pre- and postoperative radiological images were evaluated to assess volumes and volume reduction following surgery. Pathology results were recorded. For patients undergoing resections, the resection radicality was >99% in 12 patients and 95–99% in 4 patients undergoing resections. In the latter patients, additional radicality was avoided intentionally because of concern for sensitive central structures. The two biopsies yielded representative material. It was possible to use operative neuronavigation based on intraoperative ultrasound without relying on preoperative navigational imaging. Neuronavigation based solely on intraoperative ultrasound was feasible and may increase surgical safety when preoperative neuronavigational image is not feasible or unavailable.     

Cardiovascular autonomic neuropathy and subclinical cardiovascular disease in normoalbuminuric type 1 diabetic patients

Cardiovascular autonomic neuropathy (CAN) is associated with increased mortality in diabetes. Since CAN often develops in parallel with diabetic nephropathy as a confounder, we aimed to investigate the isolated impact of CAN on cardiovascular disease in normoalbuminuric patients. Fifty-six normoalbuminuric, type 1 diabetic patients were divided into 26 with (+) and 30 without (-) CAN according to tests of their autonomic nerve function. Coronary artery plaque burden and coronary artery calcium score (CACS) were evaluated using computed tomography. Left ventricular function was evaluated using echocardiography. Blood pressure and electrocardiography were recorded through 24 h to evaluate nocturnal drop in blood pressure (dipping) and pulse pressure. In patients +CAN compared with -CAN, the CACS was higher, and only patients +CAN had a CACS >400. A trend toward a higher prevalence of coronary plaques and flow-limiting stenosis in patients +CAN was nonsignificant. In patients +CAN, left ventricular function was decreased in both diastole and systole, nondipping was more prevalent, and pulse pressure was increased compared with -CAN. In multivariable analysis, CAN was independently associated with increased CACS, subclinical left ventricular dysfunction, and increased pulse pressure. In conclusion, CAN in normoalbuminuric type 1 diabetic patients is associated with distinct signs of subclinical cardiovascular disease.     

Drinking patterns, psychological distress and quality of life in a Norwegian general population-based sample

Background

The purpose of this study was to investigate possible relationships between drinking patterns, psychological distress and quality of life (QoL) in a general population-based sample in Norway.

Methods

A random sample of 4,000 Norwegian citizens, aged 18 to 79, was drawn from the National Register held by Statistics Norway.

Results

Males consumed significantly more alcohol and reported more drinking-related problems with more negative consequences, compared to females. Psychological distress increased, and all QoL domain scores decreased with increasing alcohol consumption within the group drinking alcohol at all. The excessive drinkers demonstrated the highest level of psychological distress and lowest QoL in the psychological, social relationships and environment domains. Non-drinkers reported to have poorest QoL in the physical health domain, whereas light and moderate drinkers demonstrated lowest psychological distress and best QoL. Psychological distress demonstrated substantial more importance for QoL than socio-demographic variables, alcohol consumption, alcohol dependency and negative consequences of alcohol use did.

Conclusion

The findings indicate the need for a focus on psychological distress and its negative impact upon all QoL domains. Attention should also be paid to excessive drinkers who have poor QoL (psychological, social relationships and environment domains) and a high level of psychological distress. In addition, non-drinkers reported poor physical health. Further research is needed concerning the relation between alcohol consumption, psychological distress and QoL both in general population studies and in more specific samples.