SH Patients Research Articles

American Tegumentary Leishmaniasis: Cytokines and Nitric Oxide in Active Disease and After Clinical Cure, With or Without Chemotherapy

The influence of immune response on the treatment of American tegumentary leishmaniasis is pointed by several authors, and the existence of protective immunity in self-healed patients (SH) is also suggested. Thus, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin (IL-) 10, IL-17, IL-22 and nitric oxide (NO) production was determined in PBMC culture supernatants from patients with active disease (AD) and after therapy, SH patients and healthy subjects, in response to the soluble antigen of Leishmania (Viannia) braziliensis. It was demonstrated that, during the active disease, there is a predominance of IFN-γ and TNF-α, indicating a proinflammatory phase of the response; IL-17 is also highlighted at this clinical state. Also, TNF-α was slightly increased in patients after therapy. NO secretion was noticed in SH individuals, while IL-17 appeared in low levels in these patients and seems to be regulated by NO. The presence of IL-10 was observed in all groups of patients. From this study, we can suggest that in the active disease and after clinical cure, with or without chemotherapy, specific cellular immunity takes part against Leishmania, but with some similarities between the clinical states. Thus, it indicates that the mediators herein described are necessary for the cure to occur.

Association of Lipids with Oxidative Stress Biomarkers in Subclinical Hypothyroidism

Objective. The aim of the present study was to evaluate the oxidative stress biomarkers in patients with subclinical hypothyroidism (n = 20) and health controls (n = 20). Subjects and Methods. Total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thiobarbituric acid reactive substances (TBARSs), catalase (CAT), superoxide dismutase (SOD), and arylesterase (ARE) were analyzed. Results. TC, LDL-C, TBARS, and CAT were higher in subclinical hypothyroidism patients, whereas SOD did not change. Arylesterase activity was significantly lower in the SH group, compared with the control group. Correlation analyses revealed the association of lipids (TC and LDL-C) with both oxidative stress biomarkers and thyrotropin (TSH). Thyroid hormones were correlated only with triglyceride levels. In addition, TSH was significantly correlated with TBARS, CAT, and SOD. However, no significant correlations were observed after controlling TC levels. Conclusions. We found that SH patients are under increased oxidative stress manifested by reduced ARE activity and elevated lipoperoxidation and CAT activity. Secondary hypercholesterolemia to thyroid dysfunction and not hypothyroidism per se appears to be associated with oxidative stress in subclinical hypothyroidism.

Influence of Hospital Type on Treatment and Prognosis in Patients With Non-ST Elevation Acute Coronary Syndrome

Clinical practice guidelines on non-ST-segment elevation acute coronary syndrome (NSTEACS) do not take either hospital infrastructure or the availability of a catheterization laboratory into account. The aim of this study was to determine the influence of hospital type, either with or without a catheterization laboratory, on treatment and medium-term prognosis in patients with NSTEACS. The GYSCA multicenter study (covering 15 hospitals) investigated the implementation of clinical practice guidelines in patients with NSTEACS at six hospitals with catheterization laboratories (i.e. tertiary-care hospitals; THs) and nine without (i.e. secondary-care hospitals; SHs). Patients were assessed clinically at hospital discharge and after 3 and 12 months. In total, 1133 consecutive patients were recruited: 599 (52.9%) in THs and 534 (47.1%) in SHs. The use of specific class-I interventions (i.e. aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors and statins) was more common in THs (P< .01) and more patients in THs underwent revascularization while in hospital (43% vs. 30%; P< .01). The number of SH patients who were readmitted for NSTEACS at 1 year was 5-fold greater than the number of TH patients (12.8% vs. 2.3%; P< .01), and hospital type was a predictor of an adverse event. Patients admitted for NSTEACS to a hospital without a catheterization laboratory were managed less invasively and their drug treatment was less likely to have been modified to match guideline recommendations. In addition to other well-known prognostic factors, hospital type can also have an influence on patient outcomes.

Adjustment of L‐T4 substitutive therapy in pregnant women with subclinical, overt or post‐ablative hypothyroidism

Maternal hyperthyrotropinaemia is associated with an increased risk of adverse maternal and neonatal outcomes. Physiological changes during pregnancy require an increased production of thyroid hormones (or an increase in daily substitutive doses of L-T4 in hypothyroid patients) to meet the maternal and foetal needs. The aim of the study was to evaluate variations of substitutive L-T4 doses that are able to maintain serum TSH between 0.5 and 2.5 mU/l in pregnant women with subclinical- (SH), overt- (OH) and post-ablative (PH) hypothyroidism. This was a retrospective study on hypothyroid pregnant women referred to the out-patient department between January 2004 and December 2006. A total of 185 pregnant women were studied during gestation; 155 patients (76 SH, 52 OH, 27 PH) were already on L-T4 before conception and 30 (SH) started L-T4 therapy during gestation. Thyroid function and body weight were evaluated every 4-6 weeks. In the group of patients already treated before conception, 134 (86.5%) increased L-T4 doses during gestation one or more times, eight (6%) reached a definitive therapeutic dosage within the 12th week of pregnancy, 64 (47.8%) within the 20th week and 62 (46.2%) within the 31st week. This initial L-T4 increase at the first evaluation during pregnancy was 22.9 +/- 9.8 microg/day. The final L-T4 doses were significantly different depending on the aetiology, being 101.0 +/- 24.6 microg/day in SH, 136.8 +/- 30.4 microg/day in OH and 159.0 +/- 24.6 microg/day in PH. The per cent increase of L-T4, expressed as Delta% of absolute dose, was +70% in SH, +45% in OH and +49% in PH as compared to baseline dose. In SH patients diagnosed during gestation, the starting L-T4 dose was higher than L-T4 dose before pregnancy of SH patients already treated (75.4 +/- 14.5 and 63.2 +/- 20.1 microg/day, respectively), whereas the final doses were similar. L-T4 dose was increased one or more times in 24 patients (80%), 8 reached the definitive dosage within the second trimester (33.3%) and 16 within the third trimester (66.7%). Serum TSH and FT4 measurements are mandatory in pregnant patients and the optimal timing for increasing L-T4 is the first trimester of pregnancy, though many patients require adjustments also during the second and third trimester. The aetiology of hypothyroidism influences the adjustment of L-T4 therapy and SH patients needed a larger increase than OH and PH. Close monitoring during pregnancy appears to be mandatory in hypothyroid women.

Quantitative EEG in Type 1 diabetic children with and without episodes of severe hypoglycemia: a controlled, blind study

We investigated the EEG frequency distribution by quantitative EEG (QEEG) in 28 children with type 1 diabetes and 28 age- and sex-matched control children. Among the diabetic children, 15 had experienced episodes of severe hypoglycemia (SH group) and 13 had not experienced such episodes (non-SH group). The EEG analysis was blind. Frequency analysis of 15 EEG epochs, each of 4 s duration, was performed. QEEG showed increased theta activity in the SH group bilaterally in the frontocentral region and a slight trend toward more delta activity in diabetic children than control children bilaterally in the occipital electrodes. The relative alpha amplitude was decreased in the SH group at several locations. Abnormal standard EEG (diffuse theta activity) was observed in two SH patients and one non-SH patient. All control children had normal standard EEG. We conclude that episodes of severe hypoglycemia may affect frontocentral function slightly in some diabetic children.

Treatment of Subclinical Hypothyroidism Reduces Atherogenic Lipid Levels in a Placebo-controlled Double-blind Clinical Trial

Many studies have found clinical and metabolic alterations in subclinical hypothyroidism, however, there are disagreements about the benefits of levothyroxine therapy. The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with subclinical hypothyroidism. A randomized double blind, placebo-controlled clinical assay was conducted. Sixty patients were enrolled in stratified random allocation by TSH levels that generated similar groups in average: free thyroxine levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment. The TC and LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group that received LT4 were statistically different (p=0.023 and p=0.012) from those occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab, TSH levels >8.0 microUI/ml, Body Mass Index >or=25 kg/m2, and the presence of menopause. We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary, especially in patients with TSH <8.0 microUI/ml.

Lipoprotein Alterations, Hepatic Lipase Activity, and Insulin Sensitivity in Subclinical Hypothyroidism: Response to L-T4Treatment

Subclinical hypothyroidism (sH) has been associated with atherosclerotic cardiovascular disease even in the absence of hypercholesterolemia. Our study was designed to assess the hypothesis that other pro-atherogenic parameters, such as qualitative lipoprotein changes and insulin resistance, might be present in sH. Twenty-one sH women were compared to 11 female controls matched for body mass index, menopausal status, and age. Before and after 6 months of levothyroxine (L-T(4)) treatment, we determined total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apoB levels, hepatic lipase (HL) activity in postheparin plasma samples, the chemical composition and copper-induced oxidation in isolated LDL and homeostasis model assessment (HOMA), quantitative insulin sensitivity check index, and insulinogenic index. Lipid profiles were similar between the two groups. No differences in LDL oxidability or the insulin sensitivity assessment parameters were found. HL activity was significantly lower in the sH patients: median (range), 13.1 (2.5-26.7) vs. 18.7 (7.9-28.1) micromol free fatty acids/mL, p < 0.04. The LDL-cholesterol/LDL-TG ratio was decreased in sH: 3.9 (1.8-5.5) vs. 4.7 (3.5-6.8), p < 0.02. HL negatively correlated with thyroid-stimulating hormone (TSH) levels (r = - 0.504, p < 0.01) and positively with LDL-cholesterol/LDL-TG (r = 0.46, p < 0.02). Posttreatment results for all these parameters did not differ significantly compared to baseline. Increased levels of TSH are associated to a decrease in HL activity, explaining our findings of an LDL particle rich in TG. This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.

Stapled Hemorrhoidopexy Versus Milligan-Morgan Hemorrhoidectomy

The purpose of this study was to compare the outcome of stapled hemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan technique (MM group). The goals of the study were to evaluate the efficacy and reproducibility of stapled hemorrhoidopexy and define its place among conventional techniques. A series of 134 patients were included at 7 hospital centers. They were randomized according to a single-masked design and stratified by center (with balancing every 4 patients). Patients were clinically evaluated preoperatively and at 6 weeks, 1 year, and a minimum of 2 years after treatment. Patients completed a questionnaire before and 1 year after surgery to evaluate symptoms, function, and overall satisfaction. The mean follow-up period was 2.21 years +/- 0.26 (1.89-3.07). Nine patients (7%) could not be monitored at 1 or 2 years, but 4 of these 9 nevertheless filled in the 1-year questionnaire. The patients in the SH group experienced less postoperative pain/discomfort as scored by pain during bowel movement (P < 0.001), total analgesic requirement over the first 3 days (according to the World Health Organization [WHO] class II analgesics [P = 0.002]; class III [P = 0.066]), and per-patient consumption frequency of class III analgesics (P = 0.089). A clear difference in morphine requirement became evident after 24 hours (P = 0.010). Hospital stay was significantly shorter in the SH group (SH 2.2 +/- 1.2 [0; 5.0] versus MM 3.1 +/- 1.7 [1; 8.0] P < 0.001). At 1 year, no differences in the resolution of symptoms were observed between the 2 groups, and over 2 years, the overall incidence of complications was the same, specifically fecaloma (P = 0.003) in the MM group and external hemorrhoidal thrombosis (P = 0.006) in the SH group. Impaired sphincter function was observed at 1 year with no significant difference between the groups for urgency (12%), continence problems (10%), or tenesmus (3%). No patient needed a second procedure for recurrence within 2 years, although partial residual prolapse was detected in 4 SH patients (7.5%) versus 1 MM patient (1.8%) (P = 0.194). Stapled hemorrhoidopexy causes significantly less postoperative pain. The technique is reproducible and can achieve comparable outcomes as those of the MM technique as long as the well-described steps of the technique are followed. Like with conventional surgery, anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients. Its effectiveness in relieving symptoms is equivalent to conventional surgery, and the number of hemorrhoidal prolapse recurrences at 2 years is not significantly different. Hemorroidopexy is applicable for treating reducible hemorrhoidal prolapse.

Nonthyroidal illness syndrome in patients with subarachnoid hemorrhage due to intracranial aneurysm.

We have previously reported that subarachnoid hemorrhage due to ruptured intracranial aneurysm (SH) is associated with changes in the hormonal profile in the first 24 hours after the event. We proposed that the hormonal changes observed are due to the intense stress to which the patients are exposed. However, the thyroidal hormonal profile is indicative of the presence of a nonthyroidal illness syndrome (NTIS). In this paper, we examined whether the change in the thyroid hormone profile is compatible with a NTIS. Two groups of patients were included in the study: A) 30 patients with SH (21 females and 9 males; 41.7+/-11.4 years) and B) a control group including 25 patients with benign diseases of the spine (BDS) (lumbar disc hernia or stable spinal trauma) (8 females and 17 males; 41.3+/-14.2 years). In a subgroup of eight patients of each group serum triiodothyronine (T3) and reverse T3 levels were measured. The blood samples were obtained between 8:00 and 9:00 AM. The following results were obtained: The SH group had smaller serum T3 and free T4 levels than the BDS group (p<0.05): T3 (ng/mL): SH = 58.7+/-1.1 and BDS = 74.5+/-13.9; free T4 (ng/dL): SH = 0.9+/-0.2 and BDS = 1.1+/-0.3. There was no significant difference in the serum levels of total thyroxine (T4) and thyroid-stimulating hormone (TSH) between the two groups: T4 ( microg/dL): SH = 6.9+/-1.1 and BDS = 7.4+/-2.1; TSH ( microUI/mL): SH = 1.5+/-0.8 and BDS = 1.8+/-1,0. In the sample of eight patients of each group we had the following results: T3 (ng/mL): SH = 66.8+/-3.8 and BDS = 77.2+/-1.1 (p <0.05); reverse T3 (ng/dL): SH = 32.8+/-8 and BDS = 24.7+/-2.2 (NS); T3/ reverse T3 ratio: SH = 2.6+/-0.3 and BDS = 3.3+/-0.4 (NS). Thyreoglobulin and microsomal antibodies were not detectable, except in one patient in the SH group. In conclusion, the SH patients present serum levels of T3 and free T4 significantly lower than that of BDS patients; the thyroidal hormone profile suggests that SH patients have developed the nonthyroidal illness syndrome.

Determination of IgG Subclasses and Avidity of Antithyroid Peroxidase Antibodies in Patients with Subclinical Hypothyroidism – A Comparison with Patients with Overt Hypothyroidism

Objective: To evaluate the immunoglobulin G subclasses of anti-TPO and antibody avidity in patients with subclinical hypothyroidism (sH), overt hypothyroidism (H) and a control group (C). Methods: According to the TSH, fT4 and anti-TPO antibody levels, appraised by immunometric assays, 95 female patients were divided into three groups (sH, H and C). IgG subclass levels and avidity were measured by a homemade ELISA. Results were analyzed by nonparametric tests and Spearman’s rank correlation. Results: The predominant IgG subclasses detected in both case groups were IgG1 and IgG4 with a significantly higher level of IgG4 in the sH group. Consequently, the IgG1/IgG4 ratio was significantly lower in sH patients. Conclusion: The higher levels of IgG4 anti-TPO reduced significantly the IgG1/IgG4 ratio in sH patients. These results permit to envisage that increasing this ratio could be useful as a positive predictive factor for the development of overt disease in such patients.

Fluid state and blood pressure control in patients treated with long and short haemodialysis.

Patients treated at the haemodialysis (HD) centre in Tassin, France have been reported to have superior survival and blood pressure (BP) control. This control has been ascribed to maintenance of an adequate fluid state, antihypertensive drugs being required in < 5% of the patients, although it could not be excluded that a high dose of HD regarding removal of uraemic toxins might also have been of value. The aim of the study was to assess the fluid state and BP in normotensive patients on long HD (8 h) in Tassin (group TN) using bioimpedance to measure extracellular volume (ECV), ultrasound for determining the inferior vena cava diameter (IVCD), and 'on-line' monitoring of the change in blood volume (BV), and to compare them with normotensive (group SN) and hypertensive (group SH) patients on short HD (3-5 h) at centres in Sweden. ECV was normalized (ECVn) by arbitrarily setting the median ECV (in % of body weight) in SN patients at 100% for each gender, recalculating the individual values and combining the results for male and female patients in each group. The dose of HD (Kt/V urea) was higher for TN patients than for Swedish patients who had a similar Kt/V, whether hypertensive or not. SH patients had significantly higher ECVn and IVCD than TN and SN patients. TN and SN patients did not differ significantly regarding ECVn and IVCD before and after HD. However, in a subgroup of eight TN patients, ECVn was below the range of that in SH and SN patients, due to obesity with a high body mass index. Another subgroup of 14 TN patients had a higher ECVn than most of the SN patients and also higher than the median ECVn in the SH group, without any difference in body mass index, but they were nevertheless normotensive. The fall in BV was greater in SN than in TN patients, presumably due to a higher ultrafiltration rate in SN patients. However, SH patients had a smaller change in BV than SN patients, presumably because their state of overhydration facilitated refilling of BV from the interstitial fluid. Normotension can be achieved independently of the duration and dose (Kt/V urea) of HD, if the control of post-dialysis ECV is adequate. However, this is more difficult to achieve with short than with more prolonged HD during which the ultrafiltration rate is lower, BV changes are smaller and intradialysis symptoms less frequent. The results in the subgroup of patients with high ECVn at Tassin suggest that normotension may also be achieved in patients with fluid overload provided that the dialysis time is long enough to ensure more efficient removal of one or more vasoactive factors that cause or contribute to hypertension.

A second international co-operative investigation into thiacetazone side-effects Rashes on two thiacetazone containing regimens

This report describes the rashes occurring in an international co-operative investigation into thiacetazone side-effects.The regimens studied were : •STH Streptomycin 1 g intramuscularly daily together with thiacetazone 150 mg and isoniazid 300 mg in a single tablet daily.•SH Steptomycin 1 g intramuscularly daily together with isoniazid 300 mg in a single tablet daily.•TH Thiacetazone 150 mg together with isoniazid 300 mg in a single tablet daily. Patients were allocated for 12 weeks to all 3 regimens in Algeria, Ethiopia, India, Malaysia, Mongolia, Pakistan, Singapore and Trinidad but only to the streptomycin-containing regimens in Czechoslovakia and Morocco. All the tablets were identical in appearance.Rashes occurred in 17·6 per cent of the 1,396 STH patients, 7·7 per cent of the 1,407 SH patients and 16·1 per cent of the 1,165 TH patients. Of the patients with rashes, 70 per cent of 246 STH, 61 per cent of 109 SH and 70 per cent of 188 TH developed them in the first 6 weeks and 12 per cent, 16 per cent and 11 per cent respectively in the last 3 weeks. The rashes were severe in 20 per cent of the STH, 6 per cent of the SH and 20 per cent of the TH patients, the duration was less than 30 days in 73 per cent, 68 per cent and 72 per cent respectively. The rashes led to the discontinuation of the chemotherapy in 15 per cent, 6 per cent and 13 per cent respectively. Exfoliative dermatitis was rare and occurred only in 7 (3 STH, 4 TH) patients. One (TH) patient had the Stevens-Johnson syndrome.Hypersensitivity was demonstrated to streptomycin in 35 per cent of the STH and 50 per cent of the SH patients tested, to thiacetazone in 41 per cent of the STH, 20 per cent of the SH and 60 per cent of the TH patients and to isoniazid in 2 per cent, 10 per cent and 7 per cent respectively. Hypersensitivity was to 1 drug in the majority of patients.No additional treatment was given to 51 per cent of the STH, 72 per cent of the SH and 51 per cent of the TH patients. Antihistamines were given to 39 per cent, 24 per cent and 43 per cent respectively and steroids to 11 per cent, 1 per cent and 7 per cent respectively. Desensitization was successful in 19 per cent, 7 per cent and 22 per cent of the patients with rashes and unsuccessful in 6 per cent, 3 per cent and 2 per cent respectively.The frequency of rashes on all 3 regimens varied considerably from country to country but was nearly always greater in the thiacetazone-containing regimens than the SH regimen. The frequency was high in Singapore and Trinidad and low in Czechoslovakia, Morocco and Pakistan. No rashes were reported from Ethiopia. In Trinidad the frequency of rashes was significantly higher in patients of Indian than of African descent but the differences between the Chinese, Malays and Indians in Malaysia and Singapore were smaller and non-significant.

Psychological distance as a function of length of hospitalization.

21 psychiatric patients hospitalized in a state institution for at least 3 yr. (LH group) were compared in regard to their psychological distance with 38 patients who had been in private hospitals for less than 3 mo. (SH group). Psychological distance was determined by means of a modified version of Kuethe's social schemata technique which calls for replacement of pairs of figures on a field. Although LH patients were significantly older than SH patients, it was demonstrated that age was not significantly related to distance responses. The SH group consistently placed the figures further apart than the LH, suggesting that long-term hospitalized patients have more of a desire for social involvement than patients hospitalized for briefer periods of time. The possible effects of differential severity of symptoms, differences in the social climate of the hospitals, and prolonged relative social isolation were discussed.

Acute pulmonary tuberculosis in East Africans: A controlled trial of isoniazid in combination with streptomycin or PAS

Summary Sixty-five East Africans with acute bilateral pulmonary tuberculosis, bacteriologically positive, were treated either with streptomycin 1 g. plus isoniazid 200 mg. daily (33 SH patients) or with PAS sodium 20 g. plus isoniazid 200 mg. daily (32 PH patients) for a period of twelve weeks, the treatments being allocated at random. The majority of patients in each treatment series continued on the same combination for a second twelve weeks, though in the SH series the dosage of both drugs was reduced. At the start of the trial there were more very ill patients in the SH than in the PH series. No troublesome toxic effects from any of the drugs were encountered. Nearly all the patients in both series improved clinically and bacteriologically. Thus at the end of twenty-four weeks, 93 per cent of the SH patients and 87 per cent of the PH patients showed radiographic improvement, and only 3 patients (2 SH, 1 PH) still had a positive sputum. At the end of twelve weeks the SH combination was slightly superior to the PH combination in respect of weight gain and radiographic changes; at the end of twenty-four weeks, the differences between the two regimes were smaller. In the whole twenty-four-week period 2 SH and 3 PH patients died. The SH combination took longer to diminish the bacterial content of the sputum than the PH combination, but this was associated with larger numbers of bacteria in the sputum of some of the patients in the SH series at the start of the trial. No drug resistance was encountered in either series. Changes in the character of the sputum, and reduction in its daily volume, proved to be simple and valuable indices of progress. Anaemia was present in many of the patients before treatment. This improved at the same time as the tuberculosis, without specific treatment. It is concluded that both combinations are effective, and that the PAS-isoniazid combination is a powerful and valuable form of oral chemotherapy in East Africans.