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Biomedical subjects

B Schubert

Publications and source records attributed to B Schubert.

At least 19 recordsLinked to original sources

Clinical evaluation of a prototype passive fixation dual chamber single pass lead for dual chamber ICD systems.

UNLABELLED: Dual chamber ICD systems use two separate leads for sensing. We developed and tested a new prototype of a single pass dual chamber passive fixation lead for dual chamber ICDs. METHODS AND RESULTS: The prototype was a modification of the Guidant CPI Endotak DSP lead. The additional sensing electrode for the right atrium consisted of a side-mounted porous atrial ring electrode (AR). Atrial signals were recorded from the lead in patients during normal sinus rhythm (NSR), atrial fibrillation (AFib), and/or atrial flutter (AFl) with the AR in stable contact with the atrial wall or floating. During NSR, with the AR in contact with the atrial wall, an average P wave amplitude of 7.2 +/- 1.5 mV (mean +/- SD, n = 12) was measured. After induction of Afib/AFl, the single amplitude decreased to 3.6 +/- 1.5 mV (n = 8) during AFib and 3.4 +/- 1.7 mV (n = 9) during AFl. Amplitudes dropped between 53% and 75% when the AR lost atrial wall contact. The atrial pacing threshold was 1.0 +/- 0.4 V (n = 16) when the AR was in contact with the atrial wall. CONCLUSIONS: In future dual chamber ICDs the signals from a passive fixation single pass lead could be used for atrial sensing and pacing as long as the sensing electrode for the right atrium remains in contact with the atrial wall. This system might lead to a simpler, less invasive implantation of dual chamber ICD systems.

Atrial Fibrillation

Isolation of Francisella tularensis by centrifugation of shell vial cell culture from an inoculation eschar.

A 52-year-old man was admitted to the hospital following the development of an inoculation eschar and fever six days after being bitten by a tick. He was clinically diagnosed as suffering from rickettsiosis. Eschar biopsy cultures on standard bacteriological media remained sterile. However, inoculation of cells with the homogenized specimen by the centrifugation-shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197-199, 1989) resulted in the recovery of a bacterium. Determination of the sequence of the 16S rRNA gene amplified from the organism and comparison of the sequence to other sequences identified it as a strain of Francisella tularensis, whereas the specific serology was still negative. Our findings demonstrate that the centrifugation-cell culture, which is a tool for investigation of tick-transmitted diseases, may have the potential to serve as a method for the cultural isolation of F. tularensis.

Animals

Proliferation marker Ki-S5 as a diagnostic tool in melanocytic lesions.

BACKGROUND: A discrimination between benign and malignant melanocytic lesions is not always possible by conventional histology. OBJECTIVE: Our purpose was to determine the proliferative activity in various types of melanocytic neoplasms and to appraise its value as a diagnostic adjunct. METHODS: The growth fraction was assessed immunohistochemically in 398 melanocytic lesions by means of the monoclonal antibody Ki-S5 directed to the Ki-67 antigen. In this way, a cut-off level was defined and applied to 112 lesions of equivocal histology. The revised diagnoses were correlated to the clinical courses. RESULTS: Common nevi, Spitz nevi, and melanomas exhibited significantly different proliferation indices and distinctive distribution patterns of cycling cells. In agreement, malignancy diagnosed on the basis of a growth fraction greater than 5% was confirmed by disease progression in 68% of our cases with uncertain diagnosis. CONCLUSION: Determination of the proliferative activity in melanocytic lesions may usefully complement conventional histology to improve diagnostic accuracy.

Antibodies, Monoclonal

Immunophenotyping of dermal spindle cell tumors: diagnostic value of monocyte marker Ki-M1p and histogenetic considerations.

Various studies have reported the utility of anti-CD34 staining in the differential diagnosis of dermal spindle-cell tumors. To investigate whether monoclonal antibody Ki-M1p might add practical diagnostic information, we examined a total of 120 cutaneous spindle cell neoplasms using a panel of markers. Anti-CD34 antibody QBEnd/10 consistently stained dermatofibrosarcomas, Kaposi's sarcomas, neurofibromas, and, to a lesser extent, hemangiopericytomas. A positive reaction was also found in > 18% of the dermatofibromas. Ki-M1p staining showed an intense immunoreaction in all dermatofibromas, whereas no reactivity was observed in dermatofibrosarcomas. In addition, a subset of cells was labeled in atypical fibroxanthomas and Kaposi's sarcomas. Neurofibromas, spindle-cell hemangioendotheliomas, and hemangiopericytomas were negative. Dermatofibrosarcomas and atypical fibroxanthomas also moderately expressed smooth muscle-specific actin. Immunohistochemically, a discrimination between dermatofibrosarcomas and neurofibromas was possible only by means of an antibody against the nerve growth factor receptor. We conclude that the combination of several antibodies, in particular anti-CD34 and Ki-M1p, may improve the accuracy of diagnostic immunohistochemistry in the field of cutaneous spindle cell tumors. We speculate that dermatofibroma is primarily a macrophage-rich inflammatory lesion in which cytokine secretion induces a secondary proliferation of fibroblasts, whereas dermatofibrosarcoma is likely to issue from primitive dermal cells of uncertain origin.

Antibodies, Monoclonal

Recurrent annular erythema with purpura: a new variant of leucocytoclastic vasculitis responsive to dapsone.

Annular lesions are rarely reported in the clinical spectrum of leucocytoclastic vasculitis, except in the acute haemorrhagic oedema of the skin. We report three patients who suffered from an extraordinary recurrent annular dermatitis, for 4 years in one case and for decades in the other two. The eruption was characterized by purpuric lesions that had a centrifugal evolution, creating target- or polycyclic patches disseminated on the limbs and trunk. The patients' general condition remained excellent during the attacks. All lesions spontaneously disappeared within 2 weeks, but recurred monthly. In all three cases, the histological changes were consistent with leucocytoclastic vasculitis. One patient had ulcerative colitis and another had a benign immunoglobulin A (IgA) monoclonal gammopathy. These two patients showed a good response to dapsone therapy. This dermatosis probably represents a new and rare variant of leucocytoclastic vasculitis.

Dapsone

Adrenocortical nodules in post-mortem series. Development, functional significance, and differentiation from adenomas.

In 498 consecutive autopsy cases, the adrenal glands were light microscopically and morphometrically studied. 265 (53.7%) patients showed single or multiples nodules, 25 (5.0%) adenomas. The diameter of nodules was between 0.3 to 8.0 mm and that of adenomas between 3.2 to 28.0 mm. Clinically, 265 (36.5%) patients revealed arterial hypertension. 283 (63.5%) were normotensive. For the diagnosis of adenomas, the architecture and the cell structure were more important than the size of the tumor. Normotensive patients showed more often (55.%) nodules than hypertensive patients (52.8%). Adenomas were more frequently found in hypertensive patients. There was no correlation between age, sex and nodules, but adenomas were more frequently found in females. Normotensive patients exhibited mainly one nodule, whereas multiple nodules were found in hypertensive patients. In patients with nodules arteriosclerosis with intima hyalinosis was present in 184 (56.3%) cases, in patients without nodules in 81 (47.4%) cases. Our study clearly demonstrates that no correlation exists between the occurrence of adrenocortical nodules and age or hypertension. The etiology of adrenal nodules should be considered together with the arteriopathy.

Adenoma

[Late potentials in high resolution ECG in thyroid gland dysfunction].

In this study we examined 278 patients as to the effect of thyroidal dysfunctions upon late-potential parameters in high-resolution ECG (HR-ECG). It could be demonstrated that both hyper- and hypothyroidism tend to produce late potentials. It is remarkable that even "subclinical" dysfunctions reveal significant alterations in HR-ECG. As late potentials represent a risk factor for ventricular arrhythmias these results are an additional indication that already "subclinical" dysfunctions of thyroid gland call for an appropriate therapy. In hyperthyroidism late potentials may be eliminated rapidly by propranolol even in low dosages.

Anti-Arrhythmia Agents

[Acute noninflammatory renal failure. New pathogenetic aspects in light of findings obtained in autopsy and biopsy of kidneys].

Thorough studies of kidney specimens obtained at autopsy or by renal biopsy revealed, that in noninflammatory acute renal failure oliguria/anuria is caused by increased activation o the renal renin-angiotensin system and increased generation of adenosine. At the polyuric phase moderately increased adenosine in kidney tissue seems to be the main factor responsible for decreased glomerular filtration.

Acute Kidney Injury

Fetal outcome of triplets in a Turner mosaic.

Pregnancies are now being reported resulting from fertilization of donor oocytes in women with ovarian failure. A case of triplets in a Turner mosaic is reported herein following transfers of embryos resulting from donor oocytes. She had previously demonstrated a normal sized uterine cavity by hysterosalpingography. The opinion from our group was that she should consider selective reduction but a perinatology consult thought she should have a favorable outcome. Her pregnancy was complicated by polyhydramnios, pre-term labor, and eventual fetal demise at 25 and 27 weeks of all three fetuses. Natural pregnancies in patients with gonadal dysgenesis have been reported in at least 138 patients. Many aborted or had stillbirths and this high rate of fetal mortality has been ascribed to chromosomal abnormalities. The continued use of donor oocytes will provide data to evaluate whether there will continue to be a higher spontaneous abortion rate and complications in second and third trimesters in Turner's pregnancies even in single pregnancies. The outcome of this case can at least be provided to future gonadal dysgenesis patients with triplets to help them in their decision as to whether or not to have selective reduction.

Adult

The effects of multiple gestation and selective reduction on fetal outcome.

A group of 32 women with at least 3 or more viable fetuses by sonography at approximately 8 weeks gestation were given the option of selective reduction. They were advised that this was a relatively new procedure but heretofore in a small series was not associated with a significant increase in fetal demise. Only 7 of 32 women chose this option. six of these 7 had triplets reduced to twins, 1 woman had quadruplets reduced to twins. Thirteen of 14 viable babies were successfully delivered at a mean of 36.8 weeks gestation; 2 of 7 (28.6%) delivered before 37 weeks. In contrast, 7 of 25 (24%) not having reduction lost all babies (6 triplets, 1 quadruplet). Four other women lost at least 1 of their gestations (total of 5 babies). Pre-term deliveries (< 37 weeks) occurred in 16 of 18 (88.8%) patients delivering at least 1 live baby, with a mean of 33.7 weeks gestation. Thus the high rate of total fetal loss and prematurity for multiple gestation and the low pregnancy wastage and pre-term delivery rate following selective reduction might make the latter a reasonable therapeutic option to patients interested in having the best chance of delivering healthy viable babies.

Abortion, Therapeutic

A conservative treatment protocol with human menopausal gonadotropins aimed at reducing multiple births.

In multicenter studies involving 3002 courses of human menopausal gonadotropins (hMG) therapy in 1286 patients, 20% of the patients who delivered had multiple gestations; 75% of these were twins and 25% were triplets or higher parity. Our stimulation regimen is very conservative in that we 1) try to allow a female with LPD and regular cycles but not reaching a mature follicle to first select her dominant follicle and wait until the serum E2 reaches approximately 100 pg/mL then add the hMG. With anovulatory women we frequently begin with only 75 IU hMG and gradually increase the hMG dosage. Using this approach we have usually attained at least a 70% pregnancy rate in six months. A study was performed to see if this conservative approach resulted in a decreased multiple birth rate percentage especially with triplets or more. The study was to evaluate the outcome of 241 consecutive pregnancies in which hMG was the sole therapy. There were 203 with one gestation and 38 with multiples. Twins--32; triplets--6. Thus 15% (38/241) had multiple births; six of 38 (15%) of the multiples had triplets or more. Though our multiple birth rate and especially higher parity rate appears to be lower than average no statistical difference was found. Thus even with conservative use of hMG multiple births cannot be easily avoided.

Estradiol

[Familial form of rheumatoid nodulosis].

We report a familial form of rheumatoid nodulosis where the early lesions appeared in the first years of life in a young man and his son. The numerous papular and nodular skin lesions disclosed an ulcerative evolution leaving atrophic scars mainly near the limbs' joints. In both patients the evolution was characterized by the late onset of polyarthralgias and of a non-destructive seronegative polyarthritis; intra-osseous lesions were present in the metatarsal bones in the father. Rheumatoid nodulosis is a rare disease, sometimes considered as a benign variant of rheumatoid arthritis without destructive joint involvement. A serum rheumatoid factor is inconstantly present and the intra-osseous geodes have been shown to be rheumatoid nodules exhibiting the same histological structures of palisading granulomas as the subcutaneous nodules. The main symptom of the disease is the occurrence of multiple nodules followed by the delayed onset of a polyarthritis with a benign course without systemic involvement.

Adult

[Evaluating thyroid gland function in patients with protein anomalies].

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.

Blood Protein Disorders

[Iodine supplementation in the province of Styria].

As far back as 1898 the Austrian Nobel price winner Wagner von Jauregg was the first to recommend iodination of salt as prophylaxis against endemic goitre (prevalence 48%) and cretinism (greater than 10%). In 1923 he achieved in a voluntary iodine supplementation of 5 mg KJ/kg table salt, which only lasted for a number of years. It was in 1963 when finally a mandatory iodized salt prophylaxis was introduced at the rate of 10 mg KJ/kg. In this study the effect of 25 years of iodine supplementation is investigated: Endemic cretinism, hypothyroidism, and goitre in newborns disappeared generally and endemic goitre in pupils was significantly reduced. However, due to epidemiological studies at elementary and secondary schools and army recruitment examinations we still found out endemic goitre grade I (according to WHO) mainly in female juveniles. Examinations were done by palpation, ultrasonography and urinary iodine excretion. In the above as well as in the urine of newborns and in mother's milk the iodine content was significantly lower than in iodine rich countries. Consequently a higher iodination of salt at the rate of 20 mg KJ/kg was recommended by the Austrian Society of Nuclear Medicine in 1985. This suggestion was taken up by the Austrian authorities and it will finally be instituted by law in May 1990 for the benefit of coming generations.

Adolescent

Inhibition of cardiac Na+ currents by isoproterenol.

The mechanism by which the beta-adrenergic agonist isoproterenol (ISO) modulates voltage-dependent cardiac Na+ currents (INa) was studied in single ventricular myocytes of neonatal rat using the gigaseal patch-clamp technique. ISO inhibited INa reversibly, making the effect readily distinguishable from the monotonic decrease of INa caused by the shift in gating that customarily occurs during whole cell patch-clamp experiments (E. Fenwick, A. Marty, and E. Neher, J. Physiol. Lond. 331: 599-635, 1982; and J. M. Fernandez, A. P. Fox, and S. Krasne, J. Physiol. Lond. 356: 565-585, 1984). The inhibition was biphasic, having fast and slow components, and was voltage-dependent, being more pronounced at depolarized potentials. In whole cell experiments the membrane-permeable adenosine 3',5'-cyclic monophosphate (cAMP) congener 8-bromo-cAMP reduced INa. In cell-free inside-out patches with ISO present in the pipette, guanosine 5'-triphosphate (GTP) applied to the inner side of the membrane patch inhibited single Na+ channel activity. This inhibition could be partly reversed by hyperpolarizing prepulses. The nonhydrolyzable GTP analogue guanosine-5'-O-(3-thiotriphosphate) greatly reduced the probability of single Na+ channel currents in a Mg2(+)-dependent manner. We propose that ISO inhibits cardiac Na+ channels via the guanine nucleotide binding, signal-transducing G protein that acts through both direct (membrane delimited) and indirect (cytoplasmic) pathways.

8-Bromo Cyclic Adenosine Monophosphate

Acute renal failure in man: new aspects concerning pathogenesis. A morphometric study.

The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.

ADP-Ribosylation Factor 6