A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies.

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method.

Time Stamp - A Novel Time-to-Digital Demodulation Method for Bioimpedance Implant Applications.

Bioimpedance analysis is a noninvasive and inexpensive technology used to investigate the electrical properties of biological tissues. The analysis requires demodulation to extract the real and imaginary parts of the impedance. Conventional systems use complex architectures such as I-Q demodulation. In this paper, a very simple alternative time-to-digital demodulation method or 'time stamp' is proposed. It employs only three comparators to identify or stamp in the time domain, the crossing points of the excitation signal, and the measured signal. In a CMOS proof of concept design, the accuracy of impedance magnitude and phase is 97.06% and 98.81% respectively over a bandwidth of 10 kHz to 500 kHz. The effect of fractional-N synthesis is analysed for the counter-based zero crossing phase detector obtaining a finer phase resolution (0.51˚ at 500 kHz) using a counter clock frequency ( fclk = 12.5 MHz). Because of its circuit simplicity and ease of transmitting the time stamps, the method is very suited to implantable devices requiring low area and power consumption.

Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy.

UNLABELLED: By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation. AIMS: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level. METHODS: Only BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor - I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM. RESULTS: DFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. CONCLUSIONS: Some impairment of liver function can occur in hepatitis negative thalassemic patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years.

INTRODUCTION: Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up. PATIENTS AND METHODS: A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 µIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 µIU/ml and 10 µIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH). RESULTS: A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = -0.39, P = 0.007), but no correlation was found between ferritin and TSH. CONCLUSIONS: Worsening of thyroid function was observed in 35% of the studied thalassemic patients by the age of 18 years. The lack of proper increase of TSH in response to the low circulating levels of FT4 in 13/17 (76%) of these patients indicates a relatively high incidence of defective pituitary thyrotrophic function in these patients.