Phenotype-Genotype Correlations in Three Different Cases of Adult-Onset Genetic Focal Segmental Glomerulosclerosis.

This study highlights the importance of a combined diagnostic approach in the diagnosis of rare diseases, such as adult-onset genetic FSGS. We present three adult patient cases evaluated with kidney biopsy for proteinuria, chronic kidney disease, and hypertension, which were suggestive of adult-onset genetic FSGS. Renal biopsy samples and formalin-fixed, paraffin-embedded fetal kidneys were evaluated using standard light microscopical stainings, direct immunofluorescence on cryostat sections, and electron microscopy. Clinical exome sequencing was performed for each case, and 45 FSGS-related genes were analyzed. Identifying mutations in the PAX2, ACTN4, and COL4A5 genes have prompted a re-evaluation of the previous histopathological examinations. The PAX2 mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood. The ACTN4 mutation caused distinct electron-dense aggregates in podocyte cell bodies, while the COL4A5 mutation led to segmental sclerosis of glomeruli with marked interstitial fibrosis and tubular atrophy. The identification of specific mutations and their histopathological consequences can lead to a better understanding of the disease and its progression, as well as potential treatment options.

The value of PLA2R antigen and IgG subclass staining relative to anti-PLA2R seropositivity in the differential diagnosis of membranous nephropathy.

BACKGROUND: The diagnostic performance of PLA2R and IgG subclass staining of kidney biopsies relative to anti-PLA2R seropositivity in the differentiation of primary and secondary membranous nephropathy (pMN, sMN) was examined. Besides PLA2R staining - which has a lower specificity than anti-PLA2R antibody serology - there is insufficient knowledge to decide which IgG1-4 subtype immunohistological patterns (IgG4-dominance, IgG4-dominance/IgG1-IgG4-codominance or IgG4-dominance/IgG4-codominance with any IgG subtype) could be used to distinguish between pMN and sMN. METHODS: 87 consecutive Hungarian patients (84 Caucasians, 3 Romas) with the biopsy diagnosis of MN were classified clinically as pMN (n = 63) or sMN (n = 24). The PLA2R and IgG subclass staining was part of the diagnostic protocol. Anti-PLA2R antibodies were determined by an indirect immunofluorescence test in 74 patients with disease activity. RESULTS: For pMN, the sensitivity of anti-PLA2R seropositivity was 61.1%, and the specificity was 90.0%; and similar values for PLA2R staining were 81.0%, and 66.7%, respectively. In all stages of pMN, IgG4-dominance was the dominant subclass pattern, while the second most frequent was IgG3/IgG4-codominance. The sensitivity and specificity scores were: IgG4-dominance 52.2% and 91.7%, IgG4-dominance/IgG3-IgG4-codominance 76.2% and 87.5%, IgG4-dominance/IgG1-IgG4-codominance 64.2% and 75%, and IgG4-dominance/codominance with any IgG subclass 92.1% and 70.8%, respectively. Anti-PLA2R seropositivity, glomerular PLA2R, and IgG4-dominance/codominance significantly correlated with each other. The IgG4 subclass was rarely encountered in sMN. CONCLUSION: In our series, IgG4-dominance had the highest specificity in the differentiation of MN, just as high as that for anti-PLA2R seropositivity. The specificity values of PLA2R staining and IgG4-dominance/codominance with any IgG subclass or IgG4-dominance/IgG1-IgG4 codominance were ≤ 75%. Apart from IgG4 dominance, IgG4-dominance/IgG3-IgG4-codominance also had good statistical value in differentiating pMN from sMN. As IgG subclass switching during the progression of pMN was not the feature of our cohort, pMN in Hungarian patients is presumed to be an IgG4-related disorder right from the start. Although anti-PLA2R seropositivity has become the cornerstone for diagnosing pMN, if a kidney biopsy evaluation is conducted, besides the staining of PLA2R antigen, the evaluation of IgG subclasses provides relevant information for a differential diagnosis. Even in cases with IgG4-dominance, however, malignancy should be thoroughly checked.

The effect of an exam period as a stress situation on baroreflex sensitivity among healthy university students.

Purpose: Authors investigated the effect of a university exam period on blood pressure (BP) and baroreflex-sensitivity (BRS) among healthy students.Materials and methods: Fifty-three healthy normotensive university students participated in the test. BP values and BRS were recorded once during a 14-week long semester and once during a 6-week long exam period with a Finometer device. The time-domain spontaneous BRS in lying position and after standing up was calculated with Nevrokard software. Students were divided into optimal, normal, high-normal and hypertension (HT) groups by BP values.Results: All the BRS values calculated in the exam period were significantly lower compared to the semester period in the same positions. In supine position: (semester vs. exam) up-BRS was 21.9 ± 13.2 ms/mmHg vs. 18.5 ± 11.9 ms/mmHg (p = .013), down-BRS was 22.3 ± 9.3 ms/mmHg vs. 18.4 ± 8.2 ms/mmHg (p = .019). After standing up: (semester vs. exam) up-BRS was 9.3 ± 3.3 ms/mmHg vs. 7.6 ± 3.1 ms/mmHg (p = .02), down-BRS was 9.5 ± 3.6 ms/mmHg vs. 7.0 ± 2.8 ms/mmHg (p < .0001). The number of students decreased in optimal BP group and increased in normal and HT groups in the exam period.Conclusions: A 6-week long exam period had enough stress effect to change cardiovascular parameters towards a higher risk even in healthy young people.

Observations of changes of blood pressure before and after neurosurgical decompression in hypertensive patients with different types of neurovascular compression of brain stem.

AIMS: The neurovascular pulsatile compression of the rostral ventrolateral medulla can be divided into different subtypes. The posterior inferior cerebellar artery and/or vertebral artery can compress either the rostral ventrolateral medulla or the cranial nerves IX and X or both and on left, right or both sides. METHODS: It was retrospectively investigated whether the types of neurovascular compression can influence blood pressure values. Data from 13 resistant hypertensive patients after decompression were investigated. RESULTS: Six patients had 2 compressions, two had only medulla compression, four had only nerve compression on the left side and one had 2 compressions on both sides. There was no correlation between the types of compression and the levels of blood pressure, either before or after the decompression. Both, systolic and diastolic blood pressures and pulse pressure also decreased in all cases after the decompression but the change was significant only in the group with 2 compressions on the left side. CONCLUSION: According to our data, in a severe hypertension not responding to conventional antihypertensive therapy, the surgical decompression of the brain stem independently of the types of neurovascular compression could guarantee a decrease of blood pressure and improved sensitivity to antihypertensive medication.

Investigation of cardiac autonomic and peripheral sensory neuropathy in diabetic and nondiabetic patients with hypertension.

Peripheral sensory function and cardiac autonomic neuropathy were studied in 18 nondiabetic and 10 type-2 diabetic hypertensives compared with 11 healthy controls. All the patients were treated with antihypertensive drugs. Cardiac autonomic neuropathy using Ewing method was detected in all patient groups. The current perception threshold values on peroneal nerve at 250 Hz in nondiabetic group and at 250 Hz and at 5 Hz in diabetic group were found increased compared with the controls. In conclusion, so-called typical complications of diabetes can be observed in nondiabetic hypertensives also. Our data might support the essential role of vascular factors in the development of neuropathy.

High prevalence of prehypertension and hypertension in a working population in Hungary.

BACKGROUND: Hungary has one of the highest mortality rates due to strokes among the European Union countries. As elevated blood pressure (BP) is the principal risk factor for strokes, we assessed BP levels, as well as awareness and treatment status of hypertension and prehypertension in a working population sample in Hungary. METHODS: Worksite employees in Budapest and Szeged were screened for their BP using an automated BP measuring instrument (BpTRU). BpTRU readings of heart rate (HR) were also recorded. Respondents were classified as normotensives (NT), prehypertensives (PHTN) and hypertensives (HTN) according to their BP levels, as defined by the JNC 7 guidelines. Body height and body weight were measured and body mass index (BMI) was calculated. Self-reported information regarding smoking was collected. RESULTS: In total, 2,012 respondents were recruited (1,000 white collar; 1,012 blue-collar workers), with a mean (±s.d.) age of 34.8 (±9.9) years. Of all respondents, 22.6% were identified as HTN and 39.8% as PHTN. Among HTN, 40% were unaware of their condition and only 18.5% were adequately treated. PHTN were similar in age as NT, but showed significantly higher HR. CONCLUSIONS: A high proportion of relatively young and apparently healthy Hungarian employees were diagnosed with prehypertension and hypertension. Only a small proportion of HTN had their BP controlled. BMI and HR were significantly higher among individuals with prehypertension compared to NT. Whether the high rates of hypertension, prehypertension, and low levels of control explain the high stroke mortality and unfavorable cardiovascular disease (CVD) profile of Hungary needs further study.

Neurovascular pulsatile compression and neurosurgical decompression of the rostral ventrolateral medulla in medically resistant hypertensive patients.

BACKGROUND/AIMS: In cases of severe primary hypertension not responding to conventional medical therapy, neurovascular pulsatile compression of the rostral ventrolateral medulla on the left side may be considered as an etiological factor in the hypertension. Through neurosurgical decompression, the blood pressure can be reduced in these cases, and the conventional medication can also become more effective. METHODS: The authors retrospectively analysed the changes in the blood pressure and therapy of patients with or without neurosurgical decompression over a 2-year period. The 2-year data were available for 9 operated and 7 non-operated patients with neurovascular compression. The data of control examinations performed 1, 3, 6, 12 and 24 months after the intervention (or after MR-angiography in the non-operated cases) were analysed. RESULTS: After the decompression, both the systolic and diastolic blood pressure decreased significantly and permanently in all cases, and there was an improved response to the medication. In the non-operated group, the blood pressure did not change significantly during the 2 years. CONCLUSION: In severe hypertension that does not respond to conventional therapy, neurosurgical decompression of the brain stem on the left side can guarantee a long-lasting blood pressure reduction and a better response to antihypertensive medication.

[Odontoidectomy in the treatment of medically refractory, neurogenic hypertension]. / Bazális impresszió által okozott befolyásolhatatlan hypertonia kezelése denseltávolítással.

The authors present a case of medically refractory, neurogenic hypertension where the MR examination revealed an odontoid compression of the anterior medulla as a consequence of a basilar impression. Following transoral odontoidectomy and craniocervical fixation, the blood pressure in the 24-year-old woman returned to normal, and 1 year postoperatively she remains normotensive and off all medication. This reported case provides further support to the theory that there is a subgroup of patients who may have a vascular compression of the medulla with no neurological symptoms other than hypertension.

[Therapeutic possibilities for the inhibition of the renin-angiotensin-aldosterone system]. / Terápiás lehetóségek a renin-angiotenzin rendszer aktivitásának gátlására.

The dysfunction of the renin-angiotensin-aldosterone system and its inhibition is a powerful therapeutic tool in the treatment of cardiovascular diseases. This system is a very ancient and sensitive mechanism, which reacts very much to the impacts from the environment. The system can be inhibited through four different ways; in the practice ACE inhibitors and ARBs are used mostly. Other--also beneficial--drugs might cause the over stimulation of the system. The inhibition of the RAAS system have significant impact on reduction in cardiovascular morbidity and mortality and have been shown convincingly additional benefits comparing to other treatments.

Investigation of auditory brainstem function in diabetic patients.

We performed brainstem auditory evoked potential (BAEP) examinations in 15 patients with long-standing type 1 diabetes mellitus. We applied cardiovascular reflex tests for assessment of autonomic neuropathy. The aim of our investigation was to compare the BAEP results of this patient group with those of controls and to look for the possible correlation between alteration of the auditory brainstem function and cardiovascular autonomic neuropathy. Analysis of the latencies (waves I, II, III, and V) and the interpeak latencies (I-III and I-V) of BAEP revealed a significant difference between those of diabetics and those of healthy controls. The amplitudes of waves I, III, and V were definitely lower in comparison with amplitudes of healthy controls. We observed a positive correlation between the overall autonomic score and the latencies (waves III and V) and interpeak latencies (I-III, I-V). These data support the hypothesis that long-standing diabetes mellitus and diabetic neuropathy might be revealed as a cause of certain dysfunctions of the central auditory pathways.