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Biomedical subjects

B Berner

Publications and source records attributed to B Berner.

At least 19 recordsLinked to original sources
PubMed2002

[Long-term analysis of clinical disease activity and chronic organ damage in patients with systemic lupus erythematosus].

BACKGROUND: Systemic lupus erythematosus is a chronic inflammatory and systemic disease with multiple symptoms which is often characterized by a course of exacerbations. Over the last few decades the prognosis of SLE considerably improved with >90% patients living more than 10 years with their disease. AIM OF THE STUDY AND METHODS: The aim of this retrospective-descriptive analysis of 65 patients with the diagnosis of SLE (based on the ARA criteria) was to investigate the symptoms and the laboratory values at the time of diagnosis (TD) and over a period of 10 years (10Y) in the outpatient university clinic of the Department of Nephrology and Rheumatology at Goettingen. In addition to symptoms and laboratory values, disease activity, exacerbations, chronic organ failure, and medical therapy were to be investigated. RESULTS: The long-term analysis revealed a decline in the prevalence of ANAs (TD: 95.6%; >10Y: 78.6%), ds-DNA antibodies (TD: 78.0%; >10Y: 46.7%) and pathological levels of the complement component C3 (TD: 72.7%; >10Y: 42.9%) over time. The symptoms most prevalent at the time of first diagnosis such as the typical butterfly rash (TD: 50.0,%; >10Y: 36.8%), discoid skin lesions (TD: 38.8%; >10Y: 23.5%) were noted less often after a 10 year-disease course. On the contrary the frequency of arthralgias (TD: 61.2%; >10Y: 57.9%), myalgias (TD: 26.1%; >10Y: 26.3%) and fatigue (TD: 63.0%; >10Y: 64.7%) remained stable over time. The prevalence of arterial hypertension (TD: 17.2%; >10Y: 54.5%), proteinuria (TD: 33.3%; >10Y: 66.7%) and erythrocyturia (TD: 27.8%; >10Y: 44.4%) remarkably increased during the disease course. Besides renal damage, coronary artery disease (TD: 6.0%; >10Y: 23.0%) and neurological disease (e.g., cerebrovascular insults) (TD: 10.9%; >10Y: 26.3%) were noted more often after 10 years. Of patients, 56.9% developed one or several exacerbations of the disease. In all cases, clinical symptoms correlated with an increase in the level of ds-DNA-antibodies and a decrease of C3-complement component. Other medications included immunosuppressants, antihypertensive drugs and NSAIDs. High-dose steroids were preferred as the first diagnosis (TD: 44.4%; >10Y: 11.1%), while low-dose steroids were more often prescribed after a 10-years diseases course (TD: 6.7%; >10Y: 27.8%). CONCLUSIONS: There is a shift towards secondary organ damage with a decline of the inflammatory activity in patients with SLE after 10 years of disease. These consecutive diseases are due to the primary damage of SLE as well as to medical treatment (e.g., with steroids).

Adolescent↗
PubMed2001

Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for prostate cancer.

Standard therapies for prostate cancer including radiation, prostatectomy, and hormone ablation have significant toxicities and recurrence risk. HSV-tk gene therapy may be effective in combination with radiation therapy due to complementary mechanisms and distinct toxicity profiles. Mouse prostate tumors transplanted subcutaneously were treated by either gene therapy involving intratumoral injection of AdV-tk followed by systemic ganciclovir or local radiation therapy or the combination of gene and radiation therapy. Both single-therapy modalities showed a 38% decrease in tumor growth compared to controls. The combined treatment resulted in a decrease of 61%. In addition the combined-therapy group had a mean survival of 22 days versus 16.6 days for single therapy and 13.8 days for nontreated controls. To analyze systemic anti-tumor activity, lung metastases were generated by tail vein injection of RM-1 prostate cancer cells on the same day that they were injected subcutaneously. The primary tumors were treated as before with AdV-tk followed by ganciclovir, radiation, or the combination. The number of lung nodules was reduced by 37% following treatment with AdV-tk, whereas radiotherapy alone had no effect on metastatic growth. The combination led to an additional 50% reduction in lung colonization. Primary tumors that received the combination therapy had a marked increase in CD4 T cell infiltrate. This is the first report showing a dramatic systemic effect following the local combination treatment of radiation and AdV-tk. A clinical study using this strategy has been initiated and patient accrual is ongoing.

Adenoviridae↗
PubMed2001

Pharmacokinetics of metformin gastric-retentive tablets in healthy volunteers.

The single-dose pharmacokinetics of two gastric-retentive, extended-release tablet formulations of metformin hydrochloride in fed, healthy volunteers were compared with those of the currently marketed immediate-release metformin hydrochloride product. The plasma concentration-time profiles demonstrated extended-release characteristics from the gastric-retentive tablets. The mean bioavailability from each gastric-retentive tablet was approximately 115%, relative to the immediate-release (IR) product. Cmax values were lower and tmax values were greater for the gastric-retentive tablets compared with the IR product. In contrast to conventional extended-release metformin tablets reported in the literature, these gastric-retentive tablets showed extended-release plasma concentration profiles of metformin hydrochloride and increased bioavailability compared with the immediate-release tablet.

Adult↗
PubMed2000

Vestibular neurectomy.

A brief history of the vestibular neurectomy is given. This treatment modality was introduced in Denmark by us, using the experiences obtained by the use of translabyrinthine treatment modality for vestibular schwannoma surgery. This paper presents our experiences with this type of surgery (translabyrinthine, retrolabyrinthine and retrosigmoid vestibular nerve section) from 1980 to 1996, including 43 operations in 42 patients. The patients had all been treated with conventional methods without success and were all severely handicapped by their attacks of vertigo. The mean age was 51 years, postoperative observation time between 2 and 15 years, with a mean of 6.4 years. The vertigo was controlled in 88% of the patients, while postoperative imbalance occurred in 14 patients, mainly due to the ablation of the vestibular labyrinth and not by episodic vertigo. A total of 39 patients indicated that they were satisfied with the operation. Six patients were deaf before surgery and 92% of the remaining patients retained their preoperative hearing. Postoperative complications were few, including two re-operations for CSF leaks, one patient with a slight transient facial nerve paresis and one transient VI nerve paresis. The results compare favorably with results from other authors. Retrosigmoid vestibular nerve section is an effective treatment modality to be offered to patients in whom other modalities have failed. Information about the efficacy and leniency of the treatment should be given to the patient's organization in order to diminish the fear of an intracranial intervention. Surgical experience is necessary in order obtain good results, the number of patients needing the operation is small and centralization of the treatment is mandatory.

Adult↗
PubMed2000

Age-related hearing impairment and B vitamin status.

The aim of this study was to examine, in elderly subjects, a possible association between age-related hearing impairment and vitamin B12 or folic acid status. Ninety-one consecutive subjects with pure age-related hearing impairment, 35 males and 56 females, with a median age of 78 years, range 67-88 years, were included in the investigation. All subjects underwent a thorough evaluation, including pure-tone, speech and impedance audiometry. Blood samples were drawn for determination of B12, folic acid and homocysteine and analysed by routine laboratory measurements. No significant differences in the blood parameters as a function of gender could be demonstrated and no correlations were found between B12 or folic acid and hearing levels averaged across the range 0.5-4 kHz. A weak correlation between hearing levels and homocysteine (r = 0.03; correlation coefficient 0.004) was found; however, a comparison of the hearing levels between those with increased and normal homocysteine failed to show any significant differences. In addition, no association between B12 and the speech recognition score could be found. This investigation therefore fails to demonstrate any association between hearing level and vitamin B12 or folic acid in elderly subjects.

Acoustic Impedance Tests↗
PubMed2000

Increased expression of CD40 ligand (CD154) on CD4+ T cells as a marker of disease activity in rheumatoid arthritis.

OBJECTIVES: The interaction between the activation induced surface glycoprotein CD40L (ligand) (CD154) on CD4+ T cells and its receptor CD40, which is expressed on various cell types, plays a crucial part in numerous cell mediated and humoral immune reactions that may be of pathogenetic importance in rheumatoid arthritis (RA). To further evaluate the pathogenetic role of CD40L in RA, expression of CD40L and various other T cell activation antigens as well as costimulatory molecules was investigated on CD4+ T cells in RA by flow cytometry. METHODS: Two colour flow cytometry was used to determine the percentage of CD4+ T cells expressing CD40L, CD69, CD25, HLA-DR, CD39, CD27 and CD28 in peripheral blood (PB) of 62 RA patients in comparison to 20 healthy controls (HC). Disease activity was assessed by clinical, laboratory and radiological examination. Status of clinical remission of RA was evaluated according to the ACR preliminary criteria for complete clinical remission of RA. RESULTS: CD40L was expressed on > 10% of CD4+ T cells in 29% of RA patients thus defining a CD40L(high+) patient group. Disease activity as estimated by C reactive protein, rheumatoid factor and status of clinical remission of disease (p = 0.049) was higher in this subgroup than in the RA CD40L(low+) group. Expression of CD69, CD25, and HLA-DR was significantly increased in both RA patient groups in comparison with HC. However, the percentage of CD39+ CD4+ T cells was increased only in the RA CD40L(high+) subgroup (versus HC p = 0.019, versus RA CD40L(low+) p = 0.044). Furthermore, expression of CD40L and CD39 on CD4+ T cells correlated positively as estimated by Spearman rank correlation (p<0.001). The percentage of CD4+ T cells lacking the costimulatory molecules CD27 (p = 0.002) and CD28 (p = 0.026) was increased in RA CD40L(low+) patients in comparison with HC. CONCLUSIONS: These data suggest that increased expression of CD40L on CD4+ T cells in RA indicates prolonged and increased activation of CD4+ T lymphocytes and is associated with active disease and possibly an unfavourable prognosis. Whether this phenotypically defined RA CD40L(high+) subgroup will preferentially respond to an anti-CD40L antibody treatment remains to be elucidated.

Adult↗
PubMed2000

Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry.

OBJECTIVE: A Th1/Th2 cytokine imbalance with a predominance of Th1 cytokines has been suggested to be of pathogenetic importance in rheumatoid arthritis (RA). To evaluate the role of Th1/Th2 cytokines in RA, we used intracellular cytokine flow cytometry to determine cytokine profiles of CD4+ and CD8+ T cells in 34 peripheral blood (PB) and 10 synovial fluid (SF) samples from patients with RA. Results were compared with 10 PB samples from healthy controls (HC) and 5 SF samples from patients with non-RA synovitis. METHODS: After stimulating cells with PMA and ionomycin or alternatively with anti-CD3/CD28 in the presence of brefeldin A, intracellular levels of Th1 [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were determined for CD3+CD8- (i.e., CD4+ Th1 and Th2 cells) and CD3+CD8+ (i.e., CD8+ Tc1 and Tc2 cells) T cells. RESULTS: The percentages of CD4+ and CD8+ Th1 and Th2 cytokines producing T cells (PB) were similar in patients with RA and healthy controls (HC), with a clear predominance of Th1 cytokines expressing, T cells. With regard to T cell subsets, IFN-gamma-producing T cells were significantly more frequently detected in the CD8+ subset [CD8+: median 45.1% (RA; p < 0.001), 38.2% (HC; p = 0.009) vs CD4+: 10.8%(RA), 17.0% (HC)]. Conversely, IL-2 was found in a higher percentage of CD4+ T cells [CD4+: median 33.4% (RA), 17.9% (HC) vs CD8+: 23.6% (RA), 12.3% (HC)]. Patients not in disease remission tended to have more IFN-gamma-producing CD8+ and IL-2-producing CD4+ T cells than patients in remission [CD8+: median 45.9% (IFN-gamma) vs 23.0% (IFN-gamma); CD4+: median 34.1% (IL-2) vs 18.2% (IL-2)1. In all PB samples, the proportion of T cells producing the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 did not exceed 2%. Cytokine profiles did not differ between patients receiving immunosuppressive treatment and patients treated only with nonsteroidal antiinflammatory drugs. In comparison to PB, RA SF analysis revealed a significant increase in the percentage of IFN-gamma-producing CD4+ (p < 0.001) and CD8+ T cells (p < 0.001). In addition, the percentage of IL-10-producing CD4+ (p < 0.001) as well as CD8+ T cells (p = 0.001) was significantly elevated in SF. However, production of the other Th2 cytokines (IL-4, IL-5, IL-13) was similar in SF and PB. CONCLUSION: These data indicate similar cytokine profiles of T cells in PB of RA patients and healthy controls, with a strong predominance of Th1 cytokines producing T cells in the CD4+ and CD8+ T cell subset of both groups. PB cytokine profiles did not significantly differ in patients with active and non-active disease or between patients receiving and those not receiving immunosuppressive medication. In SF, the proportion of Th1 and Tcl cells was significantly elevated compared to PB, emphasizing the local importance of these cells for inflammation. CD8+ T cells (Tc1 cells) mainly contributed to the production of IFN-gamma, indicating an underestimated role of this cell subset for local cytokine production. The upregulation of IL-10-producing Th2 and Tc2 cells in SF may reflect an insufficient effort to down-regulate chronic inflammation in the joint. Modifying this cytokine imbalance in the joints may be a promising therapeutic approach in RA.

Adult↗
PubMed1999

[Rapidly progressing renal insufficiency as the primary manifestation of systemic sarcoidosis].

CASE REPORT: We report the history of a 67-year-old patient who was admitted to hospital because of rapidly progressive renal insufficiency. The renal biopsy revealed granulomatous interstitial nephritis. The diagnosis of systemic sarcoidosis was confirmed by typical findings of bronchoalveolar lavage and of transbronchial, liver and bone marrow biopsy. Indications for sarcoidosis-related nephrocalcinosis/nephrolithiasis or glomerulonephritis were absent. Simultaneously a monoclonal gammopathy of unknown significance (MGUS) was diagnosed. While the patient having been uremic at the time of diagnosis, the administration of prednisolone effectively improved renal function. CONCLUSIONS: As a rare manifestation of sarcoidosis granulomatous interstitial nephritis can cause rapidly progressive renal insufficiency, which can effectively be treated by steroids, if distinct interstitial fibrosis is absent.

Acute Kidney Injury↗
PubMed1999

Complete heart block as a rare complication of treatment with chloroquine.

Antimalarials are well established disease modifying antirheumatic drugs. A rare and underappreciated treatment difficulty is cardiac complication, in particular conduction disturbances. We describe 2 more patients that developed complete heart block after high dose, longterm treatment. Patient 1, a 73-year-old woman with longstanding rheumatoid arthritis, had taken chloroquine (250 mg/day) for 12 years when she developed complete heart block requiring a permanent pacemaker. Patient 2, a 40-year-old woman with discoid lupus erythematosus, was taking chloroquine from 1979 until 1996. Depending on the clinical disease activity, she intermittently increased the dose from 250 to 750 mg/day. In 1994, she developed complete heart block and a permanent pacemaker had to be implanted. Intensive investigations in both cases did not reveal another underlying cause for conduction disturbances; the atrioventricular block was probably due in both cases to chloroquine related cardiac toxicity. This toxicity seems to be restricted to longterm, high dose treatment; however, it should be kept in mind in patients with preexisting conduction disturbances during longterm treatment.

Adult↗
PubMed1998

Transbuccal delivery of acyclovir: I. In vitro determination of routes of buccal transport.

PURPOSE: To determine the major routes of buccal transport of acyclovir and to examine the effects of pH and permeation enhancer on drug permeation. METHODS: Permeation of acyclovir across porcine buccal mucosa was studied by using side-by-side through diffusion cells at 37 degrees C. The permeability of acyclovir was determined at pH range of 3.3 to 8.8. Permeability of different ionic species was calculated by fitting the permeation of data to a mathematical model. Acyclovir was quantified using HPLC. RESULTS: Higher steady state fluxes were observed at pH 3.3 and 8.8. The partition coefficient (1-octanol/buffer) and the solubility of acyclovir showed the same pH dependent profile as that of drug permeation. In the presence of sodium glycocholate (NaGC) (2-100 mM), the permeability of acyclovir across buccal mucosa was increased 2 to 9 times. This enhancement was independent of pH and reached a plateau above the critical micelle concentration of NaGC. The permeabilities of anionic, cationic, and zwitterionic species were 3.83 X 10-5, 4.33 X 10-5, and 6.24 x 10-6 cm/sec, respectively. CONCLUSIONS: The in vitro permeability of acyclovir across porcine buccal mucosa and the octanol-water partitioning of the drug were pH dependent. A model of the paracellular permeation of the anionic, cationic, and zwitterionic forms of acyclovir is consistent with these data. The paracellular route was the primary route of buccal transport of acyclovir, and the enhancement of transbuccal transport of acyclovir by sodium glycocholate (NaGC) appeared to operate via this paracellular route.

Acyclovir↗
PubMed1998

Development and implementation of a breast and cervical cancer screening program in urban and rural Alaska.

Early detection of breast and cervical cancers represents the single best strategy to effect the reduction of associated morbidity and mortality. The State of Alaska identified a need to establish a service delivery system which would assure the availability of breast and cervical cancer screening services for women who are low income, under- and uninsured, and from racial/ethnic minorities. In March 1995 the Alaska Breast and Cervical Cancer Early Detection Program (AK-BCCEDP) began funding breast and cervical cancer screening services through the Centers for Disease Control and Prevention, National Breast and Cervical Cancer Early Detection Program. The purpose of AK-BCCEDP is to establish a comprehensive service delivery strategy which includes screening, tracking, referral, follow-up, public education, quality assurance, surveillance, coalition building/partnering, and evaluation. During the first year of services (March 1, 1995, to February 29, 1996) 651 women were screened for breast and cervical cancer. Higher than expected numbers of breast cancer were detected. Of the 651 women screened, four were diagnosed with invasive breast cancer and three were diagnosed with high-grade squamous intraepithelial lesions.

Adolescent↗
PubMed1996

Coronal CT of the paranasal sinuses before and after functional endoscopic sinus surgery.

Coronal CT of the paranasal sinuses and the ostiomeatal complex (OMC) was performed before and 12 months after bilateral functional endoscopic sinus surgery (FESS) in 30 patients with sinusitis and 12 patients with nasal polyposis. The extent of sinus mucosal thickening was graded, and the patency of the OMC was evaluated. After FESS, the percentage of open OMCs had increased from 42% to 83% in the sinusitis group, and from 8% to 45% in the polyposis group. There was only a small improvement in mucosal score in sinuses with opened OMC, so that the overall extent of sinus opacification before and after FESS was almost the same. Despite this, 91% of the patients reported clinical relief of symptoms. Preoperative coronal CT of the paranasal sinuses serves as an anatomical map for the surgeon, but there is no benefit of routine postoperative CT.

Adult↗
PubMed1996

High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man.

Previously, we have investigated the relationship between dissociation constant (pKa) and skin irritation potential. In the present experiment, 12 basic compounds, with varying pKa values ranging from 1.4 to 11.2, were applied on the backs of 12 healthy adult panellists. Cutaneous reactions were measured objectively, using reflectance spectroscopy and transepidermal water loss (TEWL), and evaluated subjectively with a modified Draize scale. A positive correlation between increasing pKa and skin irritation capacity, measured either visually or by reflectance spectroscopy, was found, but only mecamylamine (pKa = 11.2) induced a significant increase in transepidermal water loss. Compounds with low pKa also induced a paradoxical vasoconstriction measured by reflectance spectroscopy. Only high pKa appeared predictive of in vivo skin irritation, and these chemicals apparently induce skin irritation with only minimal disruption of the skin barrier. A simple 1-variable model is predictive of skin irritation for this series of organic permeants with increasing pKa.

Adult↗
PubMed1995

Temporally controlled drug delivery systems: coupling of pH oscillators with membrane diffusion.

A novel approach to modulate the release of a drug or an active ingredient that avoids the need for external power sources or electronic controllers is described. By changing the pH of a solution relative to the pKa, a drug, enhancer, or solubilizer may be rendered charged or uncharged. Because only the uncharged form of a drug can permeate across lipophilic membranes, a temporally modulated delivery profile may be obtained with a pH oscillator in the donor solution. Ionizable permeants have a buffer capacity, so the feasibility of coupling the mixed Landoldt pH oscillator with membrane diffusion of nicotine or benzoic acid is demonstrated for a single oscillation.

Benzoates↗