Effects of glucose-insulin-potassium infusion on ST-elevation myocardial infarction in patients treated with thrombolytic therapy

The role of glucose-insulin-potassium (GIK) infusion in the management of acute myocardial infarction is not well established. This prospective, randomized study comprised 120 patients who had ST-elevation myocardial infarction that was treated within 12 hours from symptom onset with a high dose of GIK (25% glucose, 50 IU of soluble insulin per liter, and 80 mmol of potassium chloride per liter at 1 ml/kg/hour over 24 hours) as adjunct to thrombolytic therapy (1.5 MU of streptokinase/30 to 60 minutes; GIK group) or thrombolytic therapy alone (control group). The primary end point of the study was the rate of major adverse cardiac events (MACEs) at 1 month, defined as a composite of cardiac death, reinfarction, serious arrhythmias (ventricular fibrillation and/or tachycardia), and severe heart failure. The secondary end points were the rate of MACEs at 1 year and improvement in left ventricular systolic function. The incidence of MACEs at 1 month was significantly lower in the GIK group (10% vs 32.5%, relative risk 0.24, 95% confidence interval 0.09 to 0.63, p = 0.0043). Patients in the GIK group had significant decreases in ventricular tachycardia and/or fibrillation (1.3% vs 15.0%, p = 0.003) and severe heart failure (3% vs 12.5%, p = 0.031). The rate of MACEs at 1 year was also significantly lower in the GIK group (13% vs 40.0%, relative risk 0.22, 95% confidence interval 0.09 to 0.55, p = 0.0012). After 1 year, there was a significant improvement in left ventricular ejection fraction in the GIK group (from 48 +/- 8% to 51 +/- 10%, p <0.01), which was not observed in the control group. In conclusion, high-dose GIK, used as an adjunct to thrombolytic therapy, was safe and improved clinical outcome at 1 month. The beneficial effect of GIK infusion was maintained up to 1 year.     

Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis

We report on an association of idiopathic CD4+ lymphocytopenia (ICL) and juvenile laryngeal papillomatosis (JLP) in a pediatric-aged patient. Because of a past medical history of recurrent lung infections and severe chickenpox in infancy, immunologic investigations were done at age 6 years. On several occasions, a CD4+lymphocyte count of <300 cells/mm3 was detected, supporting the diagnosis of ICL. During follow-up, both medical (interferon-alpha) and surgical treatments of JLP were only partially efficient. Our patient developed disseminated infection with Mycobacterium avium and died at 10 years of age. Human papillomavirus is an important pathogen in pediatric and adult patients with ICL. In pediatric patients with JLP who develop other unusually severe viral or opportunistic infections, immunological investigations should be considered.     

High risk of hypopituitarism in patients who recovered from hemorrhagic fever with renal syndrome

CONTEXT: Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses, is a severe systemic infection, with acute shock, vascular leakage, hypotension, and acute renal failure. Pituitary ischemia/infarction and necrosis are known causes of hypopituitarism, often remaining unrecognized due to subtle clinical manifestations. Cases of hypopituitarism after HFRS were previously only sporadically reported. OBJECTIVE: The aim of this study was to determine, for the first time, the prevalence of hypopituitarism among HFRS survivors. SUBJECTS AND METHODS: In 60 adults (aged 35.8+/-1.3 yr) who recovered from HFRS 3.7 +/- 0.5 yr ago (median 2 yr), assessment of serum T(4), free T(4), TSH, IGF-I, prolactin, cortisol, and testosterone (in males) was followed by insulin tolerance test and/or GHRH+GH-releasing peptide-6 stimulation tests. RESULTS: Severe GH deficiency was confirmed in eight of 60 patients (13.3%): in five with multiple pituitary hormone deficiencies (MPHDs) and isolated in three. Thyroid axis deficiency was confirmed in five of 60 patients (8.3%), all with MPHD. Hypothalamus-pituitary-adrenal axis deficiency was observed in six of 60 (10.0%); in five with MPHD and isolated in one. Gonadal axis deficiency was confirmed in seven of 56 male subjects (12.5%): five with MPHD and isolated in two. Overall six patients (10.0%) had a single pituitary deficit (three GH, two gonadal, and one adrenal), and five (8.3%) had MPHD. The prevalence of patients having any endocrine deficiency was 18% (11 of 60). CONCLUSION: A high prevalence of hypopituitarism after recovery from HFRS is identified, with magnetic resonance imaging revealing atrophic pituitary and empty sella. Awareness is raised to neuroendocrine consequences of HFRS because unrecognized hypopituitarism significantly affects the physical and psychological well-being.     

Association study of single-nucleotide polymorphisms in FASLG, JMJDIA, LOC203413, TEX15, BRDT, OR2W3, INSR, and TAS2R38 genes with male infertility

Infertility is a major health problem today, affecting about 15% of couples trying to conceive a child. Impaired fertility of the male factor is causative in 20% of infertile couples and contributory in up to another 30%-40%. Based on association studies, an increasing number of gene polymorphisms have been proposed to modulate the efficiency of spermatogenesis. Here, we have investigated the possible association of 9 single-nucleotide polymorphisms (SNP) in 8 different genes-FASLG, JMJDIA, LOC203413, TEX15, BRDT, OR2W3, INSR, and TAS2R38--with male infertility. We analyzed a total of 136 men with idiopathic infertility (60 azoospermic and 76 oligozoospermic) and 161 fertile controls. Our study group included individuals of different ethnic origin: 93 of the infertile men were Macedonians, 32 were Albanians, and 11 were of other origin. The control group was composed of 125 Macedonian and 36 Albanian men. The methodology included multiplex polymerase chain reaction/SNaPshot analyses, followed by capillary electrophoresis on an ABI3130 Genetic Analyzer. Of the 9 SNPs evaluated, 3 are significantly associated (P < .05) with male infertility: SNPs rs5911500 in LOC203413, rs3088232 in BRDT, and rs11204546 in OR2W3. SNP rs5911500 showed the strongest association with infertility among Albanians (P = .0001), whereas rs3088232 was most significantly associated with azoospermia among Macedonians (P = .0082). Moreover, the frequency of co-occurrence of LOC203413 minor T allele with either homozygosity or heterozygosity for the BRDT minor G allele was significantly higher among both azoospermic (6 of 60 [10%]; P = .0057; odds ratio [95% confidence interval], 8.83 [1.73-45.08]) and oligozoospermic (10 of 76 [13.2%]; P = .0002; odds ratio [95% confidence interval], 12.04 [2.57-56.47]) men in comparison with fertile controls (2 of 161 [1.2%]).     

Is There any Benefit from Expanding the Criteria for the Resection of Hepatocellular Carcinoma in Cirrhotic Liver? Experience from a Developing Country

Background

Patients with large-size (>10?cm) hepatocellular carcinoma (HCC) in Child B cirrhosis are usually excluded from curative treatment, i.e., hepatic resection, because of marginal liver function and poor outcome. This study was designed to evaluate the feasibility of the radiofrequency (RF)-assisted sequential “coagulate-cut liver resection technique” in expanding the criteria for resection of large HCC in cirrhotic livers with impaired liver function.

Methods

Forty patients with Child-Pugh A or B cirrhosis underwent liver resection from December 1, 2001 to December 31, 2008. Of these, 20 patients (13 Child-Pugh A and 7 Child-Pugh B) with advanced stage HCC (stage B and C according to Barcelona-Clinic Liver Cancer Group) underwent major liver resection. The two groups were comparable in terms of patient age, liver cirrhosis etiology, tumor number, and size.

Results

All resections were performed without the Pringle maneuver. There was no significant difference found between the two groups regarding resection time, perioperative transfusion, postoperative complications, hospital stay, and day 7 values of hemoglobin and liver enzymes. Likewise, there was no significant difference found in the overall survival between Child A and Child B patients who underwent major liver resection

Conclusions

RF-assisted sequentional “coagulate-cut liver resection technique“ may be a viable alternative for management of patients with advanced HCC in cirrhotic liver with impaired function.     

Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease

IntroductionWe evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein.Materials and methodsMeasurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements.ResultsImmunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients.ConclusionBased on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease.     

Growth hormone replacement normalizes impaired fibrinolysis: New insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency

BackgroundCardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far.ObjectiveTo investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement.DesignHospital based, interventional, prospective study.Investigated subjectsTwenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI).MethodsAnthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH.ResultsAt baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4–13.5) to 22.0(9.0–33.0) nmol/l after one month of treatment; p < 0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4–2.6) to 1.9(0.5–8.8) after one year of treatment; p < 0.01].ConclusionGrowth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications.