Renal handling of uric acid in patients with type 1 diabetes in relation to glycemic control

BACKGROUND: The aim of the study was to compare the renal handling of uric acid (UA) in 16 patients with type 1 diabetes without renal failure (age 34.8 +/- 13.3 years) and in 15 healthy subjects (age 34.9 +/- 12.6 years). METHODS: Creatinine clearance (Cr-Cl), clearance of uric acid (UA-Cl), fractional excretion of uric acid (UA-FE), and 24-h urinary UA excretion (UA-U) were determined. Glycemic control was assessed using fasting glucose, glycated hemoglobin and fructosamine tests. RESULTS: Patients with diabetes had significantly (p < 0.0001) lower serum UA concentrations compared to control group (2.8 +/- 0.7 vs. 5.7 +/- 0.8 mg/dl), and higher urinary UA excretion (813 +/- 107 vs. 423 +/- 40 mg/day), UA clearance (21.9 +/- 7.1 vs. 5.2 +/- 0.9 mL/min) and fractional UA excretion (17.1 +/- 5.5 vs. 4.8 +/- 1.3%), with higher creatinine clearance (129 +/- 16 vs. 111 +/- 12 mL/min, p < 0.005). In patients with diabetes there was a strong negative correlation between serum UA concentration and UA 24-h excretion (R = -0.79; p < 0.001). Fractional UA excretion correlated with fasting glycemia and HbA1c (R = +0.51 and +0.53; p < 0.05). CONCLUSIONS: In type 1 diabetes there is significant UA renal clearance increase, which is higher with poor glycemic control. It leads to hypouricemia despite an approximately twofold UA excretion increase and therefore despite increased UA synthesis.     

The results of newborn hearing screening by means of transient evoked otoacoustic emissions

OBJECTIVE: The incidence of sensorineural hearing loss is between 1 and 3 per 1000 in healthy neonates and 2-4 per 100 in high-risk children. Transient evoked otoacoustic emissions (TEOAEs) represent a method which can be applied to all newborns prior to hospital discharge, enabling early identification of hearing loss. The aim of the study was to evaluate the results of newborn hearing screening by means of TEOAEs. METHODS: Between 01.10.2002 and 30.09.2003, 5601 newborns born in the University Hospital in Poznan, Poland were screened with ERO SCAN (MAICO). Healthy neonates were screened in the second or third day of life and children treated in pathology unit--when their general condition was stable. The risk factors of hearing loss were recorded in a questionnaire. Children who failed the screening test or had risk factors of hearing impairment were referred to the outpatient clinic for further evaluation. RESULTS: Risk factors were identified in 739 newborns. The most often risk factors were: use of ototoxic drugs, low Apgar score and prematurity. Positive test result was obtained in 219 (3.91%) children unilaterally and in 137 (2.45%) bilaterally. In healthy children the prevalence of positive results was 3.56% and in high-risk infants 24.9%. The relative risk of positive test results was the highest in infants with positive family history (RR=7.5), congenital malformations (RR=6.7) and low Apgar score (RR=5). Of the group of 912 children, who were referred to the specialist, only 218 turned up to be assessed during the observation period and had the additional otoacoustic emission test performed. There was not any significant difference in the percentage of children with and without risk factors who turned up for the second test and in whom the result was positive (39.7% versus 40.3%). In 41.9% children with risk factors whose screening test was negative, the second exam gave positive result. CONCLUSIONS: The incidence of positive results in newborn hearing screening is much higher than the prevalence of hearing loss in general population and these results need verification by more precise methods. However, TEOAEs enable to select children who should be referred for audiological evaluation.     

Hyperprolactinemia in some Meniere patients even in the absence of incapacitating vertigo

Stress can be a significant factor influencing ear pathologies and is often reported to trigger the symptoms of Meniere's disease. Both physiological and psychological stress provokes the release of prolactin from the pituitary thus allowing the classification of prolactin as a major stress hormone. We investigated the level of the stress hormone prolactin in a Swedish population with early symptoms of Meniere's disease. The median prolactin level in the Meniere patients (n=33) was not significantly different from that of non-Meniere patients (n=23). However, in the Meniere group one female (90 year old) had prolactin levels in the upper normal range for women, one male (77 year old) had prolactin levels above the normal limit for men, and a third patient (76 year old female) presented hyperprolactinemia with more than twice the normal level. MRI confirmed a pituitary adenoma in this patient. This study provides further support for the recent report of hyperprolactinemia in some patients with long-standing Meniere's disease and presenting incapacitating vertigo in France. The data emphasize the likely implication of stress in this pathology where the stress hormone prolactin is likely to represent one actor in a complex hormonal imbalance affecting the inner ear.     

Factors affecting psychophysical tuning curves for hearing-impaired subjects with high-frequency dead regions

A dead region (DR) is a region of the cochlea where there are no functioning inner hair cells and/or neurons. DRs can be detected using the threshold-equalizing-noise (TEN) test, but psychophysical tuning curves (PTCs) are sometimes used to give a more precise estimate of the edge frequency of a DR; a shifted tip of the PTC indicates a DR. We show here that the shapes of PTCs for hearing-impaired subjects can be influenced by the detection of beats and simple difference tones (SDTs). As a result, PTCs can have tips at f_s, even when f_s falls in a DR. PTCs were measured for subjects with mild to moderate low-frequency and severe high-frequency hearing loss using sinusoidal and narrowband noise maskers (80-, 160-, 320-Hz wide): (1) in quiet; (2) in the presence of additional lowpass filtered noise (LF noise) designed to mask SDTs; (3) in the presence of a pair of low-frequency tones designed to interfere with the detection of beats (MDI tones). In condition (1), the PTCs were often W-shaped, with a sharp tip at f_s. This occurred less for the wider noise bandwidths. For subjects with good low-frequency hearing, the LF noise often reduced or eliminated the tip at f_s, suggesting that this tip was partly caused by detection of SDTs. For the sinusoidal and 80-Hz wide noise maskers, the addition of the MDI tones reduced the masker level required for threshold for masker frequencies adjacent to f_s, for nearly all subjects, suggesting a strong influence of beat detection. To minimize the influence of beats, we recommend using noise maskers with a bandwidth of 160 or (preferably) 320 Hz. In cases of near-normal hearing at low frequencies, we recommend using an additional LF noise to mask SDTs.     

Effect of pregnancy on diabetic vascular complications

OBJECTIVES: There are still controversies referring to pregnancy influence on the development of vascular complications in type 1 diabetes. MATERIALS AND METHODS: 227 diabetic women were taken into the study (109 who gave at least one birth (GB) and 118, who never were pregnant (NB)). All of patients started to be diabetic before the 15 years of age. We compared the development of vascular complications (VC) (hypertension-RR, proteinuria (P), retinopathy (R) and the age of patients, HbA1C, serum creatinine (Cr), creatinine clearance (CrCl) between the GB and NB groups. We also compared the development of VC in relation to risk factors (RF): HbA1c and duration of diabetes. RESULTS: Women who gave birth were significantly older and developed diabetes earlier than childless women. We didn't find any significant difference in duration of diabetes, HbA1c, mean blood pressure (BP), Cr and CrCl between these two groups. In the GB group in comparison to NB we noticed higher frequency of RR (11.1% vs 6.8%, OR 1.7), proliferative retinopathy (9% vs 6.8%, OR 1.4) and laser therapy (5.5% vs 3.4%, OR 1.6). In the next step we analyzed the development of VC in relation to risk factors: duration of diabetes (less or more than 20 years) and HbA1c levels (below and above 8.0%). Patients, who developed diabetes before 20 years of age were significantly older (36.3 vs 31.2 years p < 0.001), duration of diabetes in this group was longer (26 vs 14 years p < 0.001), Cr was higher (0.9 mg/dl vs 0.8 mg/dl p < 0.05)and CrCl was lower (73 mg/ml vs 86 mg/ml p < 0.05). In this group the frequency of proteinuria as well as retinopathy were higher (18.2% vs 7.9%, OR 2.59) (52% vs 9.2%, OR 10.6).We didn't find the difference in HbA1c concentration between the groups with different duration of diabetes. Higher HbA1c presented no relation to the age of patients, but correlated with lower frequency of patients without retinopathy (60.3% vs 66% OR 0.68). In this group laser therapy had to be performed more frequent (6.8% vs 1.8% OR 6.1). CONCLUSIONS: Pregnancy in diabetic patients with good metabolic control doesn't seem to be a risk factor for developing vascular complications. These complications are still strongly correlated with duration of diabetes.     

Factors affecting psychophysical tuning curves for normally hearing subjects

These experiments were conducted to clarify the influence of beats and combination products on psychophysical tuning curves (PTCs) for normally hearing subjects. PTCs for 1- and 4-kHz sinusoidal signals were determined using as maskers a sinusoidal tone and 80-, 160-, and 320-Hz wide bands of noise. PTCs obtained using the sinusoidal masker showed distinct irregularities, particularly for masker frequencies close to the signal frequency. The PTCs determined for the noise maskers were more regular. The broader the masker, the more regular were the shapes of the PTCs. To reduce the detectability of beats produced by the interaction of the signal and masker, a pair of low-frequency tones, called "Modulation detection interference (MDI) tones", was used to introduce beats at the same rate. The MDI tones reduced the threshold level of the sinusoidal masker by up to 20 dB for frequencies within 300 Hz of the signal frequency; a similar but smaller effect was found when an 80-Hz wide masker was used. Adding a lowpass filtered (LF) noise to the sinusoidal or narrowband noise masker did not affect the low-frequency sides of the PTCs, suggesting no influence of combination products. The LF noise did affect the high-frequency sides of the PTCs, but this can be attributed to it reducing off-frequency listening. To achieve a PTC whose shape around the tip is minimally affected by beats, we propose using a noise masker with a bandwidth approximately equal to the bandwidth of the auditory filter for which the PTC is measured.     

Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients

Hybrid cell vaccination was developed as therapeutic approach that aims at stimulating tumor-specific cytotoxic T-cell responses in cancer patients using hybrids of autologous tumor and allogeneic dendritic cells. We tested this concept and the efficacy of the vaccines in inducing clinical and immunologic responses in a clinical trial with melanoma stage III and IV patients. Of the 17 patients evaluated, 1 experienced a complete response, 1 a partial response and 6 stable disease with remarkably long survival times. In 11 of 14 patients analyzed, high-frequency T-cell responses to various tumor-associated T-cell epitope were induced and detectable in the peripheral blood. These immune responses were detected in clinical response patients as well as nonresponders. Failures of clinical responses in all the cases investigated correlated with loss of antigen expression and presentation. Hybrid cell vaccination thus proves effective in inducing tumor-specific T-cell responses in cancer patients.     

Loss of heterozygosity at chromosomes 3p and 17p in primary non-small cell lung cancer

BACKGROUND: Loss of heterozygosity (LOH) of selected regions at chromosomes 3p and 17p in non-small cell lung cancer (NSCLC) and the association of these abnormalities with major clinical parameters and prognosis were studied. MATERIALS AND METHODS: The study group included 92 consecutive primary NSCLC tumours and four microsatellite markers from chromosome 3p and three markers from 17p were analyzed. RESULTS: LOH of at least one locus was found in 83% of all analyzed tumours. Most frequently deletion (58%) was found at locus D3S1481 (3p14.2). Sequence deletions of D17S520 (17p12) and TP53 (17p13.1) occurred in 52% of tumours. LOH occurrence at 3p and 17p was more frequent in squamous cell carcinomas compared to adenocarcinomas (89% vs. 75%), but this difference was not significant. CONCLUSION: No significant association was found between LOH on any analyzed loci and tumour stage (TNM) and grade (G). There was no correlation between LOH and survival.     

Obstetrical hysterectomy

OBJECTIVE: Obstetrical hysterectomy still remains life saving operation. The aim of study was to determinate the frequency, indications and complications after the operation in the hospital in Zielona Góra, Poland. MATERIALS AND METHODS: A retrospective review based on hospital data of 36 patients undergoing obstetrical hysterectomy over the period of 11 years was undertaken. RESULTS: The incidence of obstetrical hysterectomy during 1990-2001 et the Department of Obstetrics and Gynaecology in the district hospital in Zielona Góra was 1: 593 deliveries. Post partum hysterectomy occurred in 0.021% of normal deliveries and 1.03% of cesarean sections. The most common indications were placenta increta and placenta accreta /61.1%/, followed by uterine atony /13.8%/ and rupture of the uterus /11.1%. The most frequent complications were shock and lesion of the urinary bladder/both 5.6%/. The maternal mortality was 2.8%. CONCLUSIONS: 1. The most common indications for the obstetrical hysterectomy are: placenta's pathologies; uterine atony and rupture of the uterus. 2. Obstetrical hysterectomy is connected with high risk of complications and maternal mortality.