Successful therapy with L-T4 in a 5 year-old boy with generalized thyroid hormone resistance

Resistance to thyroid hormone (RTH) is a rare dominantly inherited disorder caused by mutations in the thyroid hormone receptor beta gene which lead to impaired tissue responsiveness to thyroid hormone (TH). RTH is characterized by elevated free thyroid hormone and unsuppressed thyrotropin (TSH) levels. Two types of the disorder have been recognized: selective pituitary resistance and generalized resistance to TH (GRTH). Triiodothyroacetic acid has been used in patients showing hypermetabolism, and L-T4 treatment in high doses has been suggested in GRTH if patients have signs of clinical hypothyroidism such as growth retardation and developmental delay. The outcome of long-term treatment of GRTH with L-T4 has not yet been reported. We report a 5 year-old boy who presented with severe growth retardation, fatigue and speech delay. He had hyperactivity despite feeling tired easily. Elevated TH levels with unsuppressed TSH and delayed bone age were determined by laboratory evaluation and he was diagnosed as GRTH. There was no clinicical evidence of hypermetabolism. We could not demonstrate any mutation in thyroid receptor beta1, beta2 or alpha gene of this patient and his parents. L-T4 treatment was started at conventional doses (6 microg/kg), and after 3 months of treatment T4 and TSH levels were suppressed successfully. In 12 months of treatment, no side effects were detected and surprisingly clinical symptoms improved without requirement for high doses of L-T4.     

Oxygen radicals and nitric oxide levels in chondral or meniscal lesions or both

The pathophysiologic mechanism of osteoarthritis is not well known. The importance of reactive oxygen species and nitric oxide in the pathogenesis of osteoarthritis in patients with chondral or meniscal lesions or both and a search for their source were investigated. Synovial fluid samples obtained from 44 patients with osteoarthritis (16 had meniscal lesions, 12 had chondral lesions, and 16 had meniscal plus chondral lesions) were analyzed. Ten control subjects also were included. Reactive species, nitric oxide, and peroxynitrite were measured by the chemiluminescence technique. Patients with chondral lesions had significantly increased levels of O when compared with patients with meniscal lesions and the control group. However, patients with chondral or meniscal plus chondral lesions had significantly higher levels of other reactive oxygen species when compared with the control group. For the patients with meniscal plus chondral lesions, the contribution of nitrogen containing reactive species was evident. Although patients with chondral lesions had a significant increase in nitric oxide, the increase in patients with meniscal plus chondral lesions was more pronounced in peroxynitrite concentration. These reactive species will lead to tissue damage along with the mechanical damage caused by meniscal or chondral lesions or both.(2-)     

Arterial carbon dioxide markedly increases during diagnostic laparoscopy in portal hypertensive children

Several factors are responsible for hypercarbia during laparoscopic procedures. This study was undertaken because we observed a sudden increase in PaCO(2) in children with portal hypertension (PHT), which was unusual in healthy children undergoing laparoscopic procedures. Fifty-seven children underwent laparoscopic procedures under general anesthesia and were mechanically ventilated. Arterial blood samples were obtained 5 min after intubation (T(0)), 15 min and 30 min after CO(2) pneumoperitoneum (T(15) and T(30)), 5 min after desufflation (T(end)), and 10 min after extubation (T(ext)) for blood gas analysis. The changes in PaCO(2), pH, and ETCO(2) were statistically significant during the study periods in both groups (P < 0.05). The percentage of PaCO(2) increase between T(0) and T(15) was 11.5% and 20.1%, respectively, in the control group and the PHT group (P < 0.05). This increase reached 36.8% at T(30) in the PHT group, whereas the control group had a 17.2% increase (P < 0.05). ETCO(2) presented similar changes. The variability in base excess, bicarbonate, PaO(2), arterial oxygen saturation, and SpO(2) was not significant in either group (P > 0.05). The PaCO(2) increased remarkably in children with PHT undergoing laparoscopy, with no difference in intrahepatic or extrahepatic origin. Limiting the duration of CO(2) pneumoperitoneum and intraabdominal pressure and adjusting ventilatory variables to accommodate hypercarbia are of the utmost importance for such cases. IMPLICATIONS: We compared children with portal hypertension with systemically healthy children during laparoscopy. The increase in arterial and end-tidal CO(2) was remarkable in children with portal hypertension, regardless of bicarbonate changes. Managing ventilation to accommodate hypercarbia is of the utmost importance for such cases.     

A case of lupus vulgaris successfully treated with antituberculous therapy despite negative PCR and culture

A 14-year-old boy presented with a pink firm plaque with well-defined borders in the right infra-orbital skin area. On diascopy, the infiltrate exhibited a typical apple-jelly appearance. No acid-fast bacilli could be demonstrated. A polymerase chain reaction (PCR) assay did not reveal the presence of mycobacteria in a lesional biopsy sample. Culture of biopsied tissue on Loewenstein-Jensen medium was negative. Although the tuberculosis culture and PCR did not confirm tuberculosis, a diagnosis of lupus vulgaris was made considering the clinical and histopathological findings. After a 9-month antituberculous therapy, the lesion disappeared. We believe that a diagnosis of lupus vulgaris still depends more on clinical and histopathological findings than on tuberculosis culture or PCR.     

A comparison of pre-dropout and temporary rupture sessions in psychotherapy

Although numerous studies have investigated the relationship between the therapeutic alliance and dropout, most have focused on the relationship between alliance quality and psychotherapy outcomes. Objective: To compare sessions with therapeutic alliance ruptures and two sessions prior to treatment dropout (pre-dropout) in terms of rupture subtypes, psychotherapists’ behavior, attitudes, and session content. Method: We implemented quantitative methods to select the sessions and qualitative methods to analyze them. We analyzed 16 temporary rupture sessions from 12 therapist–patient dyads and 16 pre-dropout sessions from 8 different therapist–patient dyads. The sessions originate from clinical psychology Master’s or Doctoral students under supervision in either cognitive behavioral or schema therapy. Pre-dropout sessions were considered unrepaired rupture sessions while rupture sessions were subsequently repaired. Results: Results revealed apparent differences and similarities between the session types in positive and negative psychotherapist behaviors, content intensity, and the type and frequency of ruptures. We explored three new rupture subtypes: attributing positive developments to other sources, indirect speech, and sarcastic hostility. Conclusions: A striking implication is that the frequency of positive and negative psychotherapist behaviors, ruptures, and session content is more likely to decrease in the pre-dropout sessions than in the temporary rupture sessions.     

Cognition in 4-11 year old children in Turkey

OBJECTIVES: The purpose of this study was to determine the relationship among age, sex and academic performance with cognitive ability on healthy age groups. METHODS: The subjects were 71 children, aged 4-11 years (x = 7.11). The children were divided into four age groups: 22 of the 71 children were at kindergarten and 49 children were in primary education. Thirty nine children were girls and 32 were boys. Twenty six children had good academic achievement and 23 did not. Each child was tested on the LOTCA battery by the Occupational Therapy Unit of Hacettepe University School of Physical Therapy and Rehabilitation. In this study, seven subtests were used from LOTCA (Loewenstein Occupational Therapy Cognitive Assessment). These are orientation for place, orientation for time, overlapping figures, praxis, reproduction of a two dimensional model, drawing a clock, and categorization. RESULTS: Statistical analysis of the relationships demographic variables, academic achievement and performance on the battery revealed that age was significant, sex was insignificant and academic achievement was significant when correlated with cognitive abilities. CONCLUSIONS: The results suggest that cognitive abilities tested show some differences. For this reason, in the school or other educational settings, children who have low academic achievement should be assessed also for cognitive abilities and then provided with occupational therapy.     

The effects of levodopa use on diffusion coefficients in various brain regions in Parkinson's disease

We aimed to evaluate the effects of l-dopa use on apparent diffusion coefficient (ADC) values of different brain regions in Parkinson's disease (PD) patients. Thirty-five subjects underwent magnetic resonance imaging (MRI), including 21 PD patients (13 men, 8 women; mean age, 63 years ± 8), and 14 sex and age-matched control subjects. PD patients were separated into two groups according to the duration of l-dopa usage: patients using l-dopa less and more than 1 year. According to the disease duration two other groups were formed: patients diagnosed less and more than 1 year. Unified Parkinson Disease Rating Scale (UPDRS) scores of PD patients were detected. Diffusion weighted images (DWI) and ADC maps of patients and controls were evaluated and regional ADC (rADC) measurements were performed. Patients’ age was not significantly different between groups. UPDRS was significantly different between the patient groups. There was no significant difference of rADC values between PD and control groups, and within the different PD groups. Short- and long-term l-dopa usage in PD patients did not cause any change rADC values in various brain regions.     

Acute cigarette smoking-induced hemodynamic alterations in the common carotid artery--a transcranial Doppler study--.

BACKGROUND: Cigarette smoking has been shown to temporarily alter cerebral flow velocity and vasomotor reactivity, so the aim of this study was to assess the acute effects of smoking a single cigarette on the common carotid artery (CCA) hemodynamics in healthy nonsmokers. METHOD AND RESULTS: Using a 7.0 MHz linear transducer of a computed sonography system, the CCA hemodynamics, including the diameter of the left and right CCA, peak systolic velocity, maximum end-diastolic velocity, time-averaged maximum velocity pulsatility index, resistivity index, flow volume, diameter and area of the CCAs, were measured in 16 healthy nonsmokers before and immediately after smoking a cigarette. Compared with the baseline, heart rate and blood pressure significantly increased, the diameter, flow volume and area of each CCA were unchanged, and the pulsatility index and resistivity index were significantly altered after smoking. In addition, the peak systolic velocity, maximum end-diastolic velocity and time-averaged maximum velocity were significantly altered after smoking. CONCLUSIONS: Cigarette smoking significantly altered the CCA hemodynamics in nonsmokers, probably as a consequence of enhanced adrenergic activity.     

Studies of Ancient Lice Reveal Unsuspected Past Migrations of Vectors

Lice are among the oldest parasites of humans representing an excellent marker of the evolution and migration of our species over time. Here, we analyzed by real-time polymerase chain reaction (RT-PCR) developed in this study the mitochondrial DNA of seven ancient head louse eggs found on hair remains recovered from two sites in Israel: 1) five nits dating from Chalcolithic period (4,000 bc) were found in the Cave of the Treasure located at Nahal Mishmar, in the Judean Desert and 2) two nits dating from Early Islamic Period (ad 650–810) were found in Nahal Omer in the Arava Valley (between Dead Sea and Red Sea). Our results suggest that these eggs belonged to people originating from west Africa based on identification of the louse mitochondrial sub-clade specific to that region.Head lice (Pediculus humanus capitis) and body lice (P. humanus humanus) are strict bloodsucking ectoparasites of humans, and each species lives in a specific ecological niche: hair for head lice, clothing for body lice.¹ Hundreds millions of children worldwide are continually infested by head lice unrelated to hygienic conditions, resulting in insomnia and itching.² Body lice exclusively infest populations exposed to stressful life conditions, such as the homeless, prisoners, and war refugees, and can serve as a vector for three serious humans diseases, namely, epidemic typhus, trench fever, and relapsing fever caused by Rickettsia prowazekii, Bartonella quintana, and Borrelia recurrentis, respectively.¹ Body lice are also suspected to be able to host and transmit Yersinia pestis, the agent of plague.³ Genetically, human lice are distributed into three mitochondrial clades (A, B, and C), whereby only Clade A comprises head and body lice.⁴ Clade A is found on all continents, whereas Clade B, with an assignment of an American origin, is present in Europe and Australia and was recently characterized in north Africa. Finally, Clade C is to date limited to Africa and Asia.⁵Lice are among the oldest parasites of humans, thus representing an excellent marker of the evolution and migration of the Homo species over time.⁴ For centuries, archaeologists excavating soil in different locations around the world have found nits, lice, and/or combs on mummies or human remains with ages varying between 300 and 10,000 years (see reference⁶ for a review). The most ancient specimens (nits from hair, 10,000 years old) were found in Brazil, South America.⁷ However, few molecular data on ancient lice are available. In 2008, Raoult and others⁸ showed that the most prevalent and well-distributed clade of lice (A) had a pre-Columbian presence on the American continent. In 2013, Boutellis and others⁹ confirmed this result and demonstrated that Clade B also had a presence of at least 4,000 years in America and that Clades A and B could live in sympatry.In this work, we obtained and analyzed ancient head louse eggs recovered from Israel dating from two different periods, namely, the Chalcolithic (4,000 bc) and early Islamic periods (ad 650–810).In 2014, two lots of ancient head louse nits recovered from human remains in Israel were sent to our laboratory for molecular analysis. A total of seven samples were examined. Five operculated nits were found on hair remains in the Cave of the Treasure located at Nahal Mishmar, in the Judean Desert, which date to the Chalcolithic period.¹⁰ The other two nit samples were found on human hair remains belonging to a population who lived in Nahal Omer in the Arava Valley (between Dead Sea and Red Sea) during the Early Islamic period (ad 650–810). The site appears to have been a way station on the north–south Arava route and on the Spice Route between Petra and Gaza.^11,12 The operculum on the eggs was most likely detached during the centuries, but the embryos were still present inside the eggs.The nits were photographed using an Axio Zoom V16 (Carl Zeiss AG, Oberkochen, Germany).All precautions to avoid contamination by modern DNA templates were taken, and negative controls were used at each step of the study. Each experimental stage was performed in a clean room each of which was located in a different building free of P. humanus and its DNA. Each egg louse was rinsed twice in sterile water for 15 minutes, and then total genomic DNA was extracted from each egg louse by using a QIAamp Tissue Kit (Qiagen, Hilden, Germany) as described by the manufacturer.To determine the clade of the specimens, an 89-bp fragment of the mitochondrial cytochrome b gene (cytb) was targeted. A sensitive tool based on the real-time polymerase chain reaction (PCR) with a hydrolysis probe that was useful to detect and amplify ancient DNA was developed. A pair of primers (the reverse primer was degenerated) that can amplify the different known clades of lice was used: cytbF (5′-AGTGTGAGGAGGGTTTTCAG-3′) and cytbR (5′-CAAACCCCAAYAAVAYAAACGG-3′). A TaqMan^© FAM-labeled probe (Applied Biosystems, Courtaboeuf, France) that contained nonfluorescent quencher conjugated to a minor groove binder (MGB) at the 3′ was designed: FAM-CTACTTTAGAGCGGTTGTTTACTC-MGB.Real-time PCR was performed using the CFX96 thermal cycler (Bio-Rad Laboratories, Foster City, CA). The final reaction volume of 20 μL contained 3 μL of the DNA template, 10 μL of 2× QuantiTect^™ Probe PCR Master Mix (Qiagen), 0.5 μM of each primer and 0.2 μM of the FAM-labeled probe. The thermocycling parameters consisted of 95°C for 15 minutes and 40 cycles of 95°C for 10 seconds and 60°C for 30 seconds. No template controls (NTCs) were included in real time PCR (RT-PCR) assay.The products of the real-time PCR amplifications were sequenced using the 3130XL genetic analyzer (Applied Biosystems) with the BigDye Terminator v1.1 cycle (Applied Biosystems, Foster City, CA). ChromasPro software (Technelysium Pty, Queensland, Australia) was used to analyze the obtained electropherograms for each sequence.Nucleotide sequences were aligned using CLUSTAL X 2.0.11 (http://www.softpedia.com/get/Science-CAD/Clustal-X.shtml),¹³ and pairwise comparisons were conducted with MEGA6 (http://www.megasoftware.net/).¹⁴ Phylogenetic analyses were based on maximum-likelihood (ML) algorithms.The appearance of nits under the microscope shows that they were well preserved despite the many centuries spent underground. As shown in Figure 1 , we can distinguish the eyes, legs, and claws of embryos still inside the operculated nits.Open in a separate windowFigure 1.Operculated head louse egg recovered from Israel dating from Chalcolithic period (4,000 bc).RT-PCR was positive for the seven samples of ancient DNA tested (32 < C_t < 34). The C_t value was 20 in the positive control; no fluorescence was detected in the negative control.A ML phylogenetic analysis performed for the cytb gene showed that the ancient hair nits belonging to the Chalcolithic and early Islamic periods are part of Clade C. Within Clade C, these nits form a sub-clade with lice found in Senegal (Figure 2 ). Nonetheless, the ancient DNA sequences are quite unique and are different compared with known sequences of contemporary lice.Open in a separate windowFigure 2.Maximum-likelihood (ML) phylogram of cytochrome b gene. ML bootstrap that support values greater than 50 are located above the nodes. Mitochondrial clade memberships are indicated to the right of each tree.In this work, the first molecular data on lice infesting the ancient inhabitants of the Near East were compiled. The tool implemented here based on the real-time PCR was effective in preventing the difficulties associated with the analysis of ancient DNA, which is often damaged or in a very low concentration.¹⁵Interestingly, this study reveals the presence of a mitochondrial genotype, Clade C, in a Near East region that has thus far only been found in Africa (Ethiopia and Senegal) and Asia (Nepal).⁵ Specifically, these old nits are included in a subgroup in Clade C comprising contemporary lice that are characterized only in west Africa. The presence of this genotype in the Near East is necessarily linked to migration flows of humans through the ages. The slave trade practiced by Arab tribes to supply the Near and Middle East in manpower existed for a long time.¹⁶ The genetic information available today from humans suggests that significant gene flow most likely occurred within the past ∼2,500 years between sub-Saharan African and Near East populations.¹⁷In conclusion, real-time PCR adopted in this study showed to be a fast, sensitive, and specific tool that is fully compatible with the analysis of ancient DNA. Through the results obtained in this work, we can affirm that the study of ancient lice is very useful to understand the migration patterns of humans, their lice, and therefore the flow of louse-borne pathogens.