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Biomedical subjects

F Koerner

Publications and source records attributed to F Koerner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma of the breast.

Invasive lobular carcinoma comprises approximately 10% of human mammary cancers, yet little is known about the molecular basis of this carcinoma. Because cyclin D1 plays a role in the pathogenesis of breast carcinomas of the ductal type, we hypothesized that this confirmed oncogene might also participate in the development of lobular carcinomas. We sought to determine the frequency of cyclin D1 protein overexpression in invasive lobular carcinoma, to investigate the cause of the protein accumulation, and to identify the effects of high levels of the protein on the regulation of the cell cycle. The study group comprises 27 indisputable cases of invasive lobular carcinoma showing varying degrees of cytological atypia. Immunohistochemical staining using well-characterized monoclonal and polyclonal antibodies disclosed cyclin D1 protein in the majority of the invasive lobular carcinoma cells in 80% of the tumors. In marked contrast, only rare cells of the noninvasive component (lobular carcinoma in situ) in the same tissue sections showed positive staining. Southern blotting of nine cases did not reveal evidence of cyclin D1 gene amplification. Immunohistochemical staining for Ki-67, a protein present in all dividing cells, showed that most cells positive for cyclin D1 did not stain for Ki-67. We conclude that the vast majority of invasive lobular carcinomas show overexpression of cyclin D1 protein. The absence of cyclin D1 protein expression in the noninvasive cells suggests that the molecule plays a role in the progression to the invasive form of lobular carcinoma. In contrast to the ductal types of breast cancer, cyclin D1 gene amplification does not seem to cause the cyclin D1 protein overexpression in lobular cancers. The lack of correlation between cyclin D1 and Ki-67 expression suggests that the cyclin D1 oncogene acts through mechanisms other than simple acceleration of the cell cycle clock in this subtype of human breast carcinoma.

Breast Neoplasms↗
PubMed1998

Optic neuropathy associated with sleep apnea syndrome.

OBJECTIVE: The study aimed to determine ocular abnormalities in sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. DESIGN: The study design was a case series. PARTICIPANTS: Nine patients referred for evaluation of suspected SAS participated. INTERVENTION: Complete ophthalmologic examination, including computerized perimetry, was performed. MAIN OUTCOME MEASURES: Correlations between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and to grade SAS, and visual field indices using the Spearman rank correlation coefficient (r(s)) were measured. RESULTS: One patient was excluded from the statistical analysis because of optic nerve drusen with constricted visual fields, another because of tilted discs with corresponding temporal visual field defects. All three patients with severe SAS and one patient with moderate SAS had relative nasal arcuate visual field defects; two patients with severe SAS also had paracentral relative defects. One patient with normal polysomnographic result and two patients with mild or moderate SAS had normal visual fields. The RDI correlated positively with the mean visual field defect (r(s) = 0.81, P < 0.05) and with the visual field loss variance (r(s) = 0.78, P < 0.05). The clinical ophthalmologic examination results were normal in all seven patients. In two of the three patients with severe SAS treated with continuous positive airway pressure (CPAP), visual field defects remained stable over 18 months. The patient with optic nerve drusen also had severe SAS and was, therefore, treated with CPAP. His constricted visual fields improved dramatically after treatment. CONCLUSIONS: Visual fields of patients with SAS showed defects consistent with an optic neuropathy. The CPAP therapy seems to stabilize or even reverse visual field defects.

Adult↗
PubMed1998

[Eye injuries caused by air bags].

BACKGROUND: Since the introduction of Airbag several reports about airbag-associated ocular injuries where published. PATIENTS AND METHODS: Here we report about four patients who were seen and treated in the university eye clinic Bern the last two years. RESULTS: The injuries included alkali burns, mechanical erosions and contusion of the globe associated with ruptures of the choroid and retinal detachment. Injuries were strictly unilateral in all cases, two affecting the right eye, two the left eye. Two cases healed without any residual lesions, while the other two showed a persistent reduction of visual acuity. CONCLUSIONS: The airbag is certainly a lifesaving device in modern passenger vehicles. Nevertheless severe eye injuries can be caused by these devices. Further research and development concerning the volume of the inflating gas, the size of the airbag as well as the speed of the vehicle at which the airbag is activated, should be continued.

Accidents, Traffic↗
PubMed1998

Selective intra-arterial fibrinolysis of acute central retinal artery occlusion.

BACKGROUND AND PURPOSE: Occlusion of the central retinal artery (CRAO) causes a sudden decrease of monocular vision. Because early restoration of blood flow may improve outcome, we attempted to treat CRAO with selective intra-arterial fibrinolysis. METHODS: Intra-arterial fibrinolysis was performed within 6 hours after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU) was given through a microcatheter into the ophthalmic artery over 10 to 90 minutes. For comparison, the history and visual outcome of 15 control patients who did not receive fibrinolytics were evaluated. In both groups some of the patients underwent paracentesis and/or received carboanhydrase inhibitors. RESULTS: Patients who underwent fibrinolysis fared better than control patients (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients (35. 3%) vision improved slightly. They were able to count fingers, detect hand movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was without effect. Among control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%) minimal, and 10 (66.7%) no improvement of vision. CONCLUSIONS: A complete or marked improvement of visual acuity was achieved in one third of intra-arterial fibrinolysis patients but in none of the control patients. Intra-arterial fibrinolysis seems to have the potential to "lighten" the spontaneously poor outcome of CRAO.

Acute Disease↗
PubMed1996

Diplopia from skew deviation in unilateral peripheral vestibular lesions.

Vertical diplopia from skew deviation is well described in brainstem lesions. The phenomenon can also result from peripheral vestibular lesions. During the past years, we have observed these ocular changes in the acute stage following unilateral vestibular neurectomy and labyrinthectomy (n = 13), as well as in series of patients suffering from idiopathic sudden unilateral peripheral vestibular or cochleo-vestibular deficit (n = 5). Diplopia from skew deviation was noted immediately following ablative vestibular procedures; in patients with idiopathic vestibular deficit, it was observed as an associated sign. In all patients, clinical evaluation revealed an acute unilateral peripheral vestibular loss, with spontaneous nystagmus toward the unaffected ear and absence of nystagmic response to caloric testing on the affected ear. Skew deviation was measured using the Hess-Weiss test, which is based on the haploscopic principle. Static visual vertical was evaluated with the original methods of vertical frame and Maddox rod techniques. Photographs were made of the ocular fundi, to measure the degree of cyclotorsion of both eyes. In our patients, we found skew deviation with hypotropia of the eye that was ipsilateral to the affected ear and conjugated cyclotorsion and tilt of the static visual vertical on the side of the affected ear. Skew deviation was the first sign to disappear within a few days; conjugated cyclotorsion and tilt of the static visual vertical persisted for weeks to months. The eye-head postural reaction, consisting of head tilt, conjugated eye cyclotorsion, skew deviation, and alteration of vertical perception directed toward the side of the lesion, is known as the Ocular Tilt Reaction (OTR). The mechanism is presumably related to a lesion of the otolithic organs and/or to changes in the afferent graviceptive pathways. In man, the OTR is often mild and unrecognized, masked by spontaneous nystagmus and marked neuro-vegetative symptoms. Our observations indicate that skew deviation, as a part of the OTR, occurs in patients with sudden peripheral vestibular lesions, whether surgical or non-surgical in origin.

Adult↗
PubMed1996

Restricted applicability of the polymerase chain reaction for the diagnosis of ocular toxoplasmosis.

The laboratory confirmation of ocular toxoplasmosis has been reported to be facilitated by the polymerase chain reaction (PCR) technique in anterior chamber taps. We utilized PCR specific for a sequence of the Toxoplasma gondii B 1 gene with a length of 194 bp. The sensitivity was adjusted to ten genomic copies per sample in stained gel and two copies after DNA hybridization using a digoxygenin-labeled probe. We amplified DNA from 43 aqueous, 14 serum, and 32 white blood cell (WBC) samples obtained from 31 consecutive otherwise healthy patients with the clinical diagnosis of ocular toxoplasmosis. In the series investigated, 1/43 aqueous samples and 2/32 WBC samples were found to contain detectable amounts of target DNA. An inhibition of the PCR by the aqueous humor as a reason for the low detection rates was excluded. Thus, we conclude that either the sensitivity of aqueous humor PCR is not sufficient for use in the routine diagnosis of ocular toxoplasmosis in immuno-competent individuals or the anterior chamber is not the proper compartment for investigation of this protozoal disease using this approach.

Adult↗
PubMed1995

Flow cytometry in node-positive breast cancer: cancer and leukemia group B protocol 8869.

This report describes a companion flow cytometry study (Cancer and Leukemia Group B (CALGB)--8869) using tumors derived from patients enrolled in a large randomized clinical trial (CALGB-8541) performed on 1,572 patients with early stage, node-positive breast cancer. The CALGB initiated an adjuvant breast cancer trial in 1985 to determine if dose intensification (dose of drug per unit time) of chemotherapy was related to relapse-free and overall survival. Patients were randomized by pretreatment clinical variables to one of three different dosage regimens of chemotherapy. Using a tumor enrichment procedure, 442 paraffin-embedded blocks were analyzed by flow cytometry, and S-phase fraction (SPF) was analyzed by three different methods. Ploidy analysis was performed using standard procedures. Tissue from 90% of the patients was suitable for ploidy analysis, whereas only 68% could be assessed for SPF. With a median follow-up time of 80 months, our results show that ploidy status had no clinical utility, whereas high SPF predicted poorer overall survival. The rectangular fit model for SPF was more predictive of outcome than both the area fit model and a computer fit model (modfit) for SPF. In univariate analysis, patients with a low SPF (< 10%) had a better prognosis than those patients with a high SPF (> 10%), but they responded equally well to the different treatment regimens. Patients with high SPF (> 10%) had longer relapse-free and overall survival to high dose chemotherapy compared to low or standard dose chemotherapy. Multivariate analysis indicated that treatment intensity as well as the number of positive nodes, tumor size, steroid receptor status, and c-erb B-2 expression were significant in predicting overall and disease-free survival. The multivariate analysis, however, revealed that SPF was significant in predicting overall but not disease-free survival, but there was no longer any relationship among SPF, dose intensity, and outcome.

Breast Neoplasms↗
PubMed1995

Retinopathy of prematurity.

This review deals with retinopathy of prematurity (ROP), a disease characterized by retinovitreal neovascularization, eventually retinal detachment and blindness. Due to the increasing number of extremely premature newborns, it is becoming more frequent. ROP of all stages occurs in 25-35% of surviving premature newborns of gestational age up to approximately 35 weeks. Stages 3 or more occur in 5-10%, blindness in 3-5% of very immature babies. The incidence is inversely related to gestational age. Classification is internationally unified (ICROP) and describes 5 stages. Its pathogenesis has not yet been clarified. More or less proven risk factors are retinovascular immaturity, hyperoxia and possibly circulatory and respiratory instability. Prophylaxis consists in avoiding hyperoxia, and probably also in keeping the extremely premature newborn stable. Ophthalmologic examinations must be performed by ophthalmologists experienced in this field or under their direct responsibility and must be standardized. Treatment of ROP can be carried out at a certain stage by coagulation therapy.

Gestational Age↗
PubMed1995

Screening for retinopathy of prematurity after surfactant treatment.

Surfactant administration in premature infants is supposed to induce rapid changes in tissue oxygenation. It might therefore modify the risk of developing retinopathy of prematurity (ROP). We have been using the so-called safety index [equation see text] to calculate the number of infants at low risk to develop ROP stage 3 or higher (SI > or = 1) after administration of two preparations of a surfactant. The study population consisted of 255 prematures of < or = 2000 g birth weight treated with surfactant for respiratory distress syndrome in Switzerland between 1991 and 1993. Of these infants, 29 received a natural surfactant (Curosurf), and 226 infants were treated with the synthetic surfactant Exosurf. Reduction of fraction inspired oxygen (FiO2) was significant within 3 and 6 h and was more pronounced in infants having received natural surfactant. An SI > or = 1 was calculated in 106 of the 226 infants (47%) treated with Exosurf. Only one of these infants developed ROP stage 3 in one eye (no ROP in the fellow eye) whereas 12 infants with ROP stages 3 or 4 had an SI < 1. Seven of the 29 infants treated with natural surfactant had an SI > or = 1; none of these infants developed ROP > stage 2. According to this survey, the risk of developing severe stages of ROP does not increase in low birth weight infants who have been treated with surfactant. Irrespective of a surfactant therapy, the calculation of the SI is useful for substantially reducing the number of prematures who need intensive ophthalmological follow up.

Biological Products↗
PubMed1994

c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.

BACKGROUND: The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy. METHODS: Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation. RESULTS: Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression. No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis. There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression. CONCLUSIONS: There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression. Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy.

Adult↗
PubMed1994

Retinopathy of prematurity and bilirubin--no clinical evidence for a beneficial role of bilirubin as a physiological anti-oxidant.

The prevention of retinopathy of prematurity (ROP) remains a persistent problem. A previous report has focused on the possible protective effect of bilirubin on the development of ROP. These results still await clinical confirmation by other research groups. Therefore, we undertook a retrospective clinical study trying to confirm this attractive hypothesis. Twelve premature newborns under 32 weeks of gestation with ROP stage 3-4 were matched for gestational age with 12 infants without ROP. Data were collected about the infant's characteristics, medical illnesses, ventilatory settings and treatments. The total serum bilirubin concentrations between the 1st and 8th postnatal day were also gathered. The two matched groups were comparable as to their basic data, clinical characteristics and treatment, except for a slight, but significant longer duration of phototherapy for group ROP 0 (mean, 50.2 h; SD 48,6 vs 31.6 h; SD 42.7 in ROP 3-4; P = 0.02). No statistical difference relative to bilirubin was found between the two groups, neither when expressed as daily mean concentrations, nor as area under the curve (AUC) (mean, ROP 0: 17876.7; SD 6077.3 vs 18888.4; SD 55552.7 in ROP 3-4; P = 0.404) or AUC/h (mean, ROP 0: 135.1; SD 36.3 vs 144.1; SD 23.2 in ROP 3-4; P = 0.515). Our findings do not confirm the hypothesis of a clinically measurable, beneficial role of bilirubin on the development of ROP.

Antioxidants↗
PubMed1992

Clinical use of recombinant plasminogen activator for intraocular fibrinolysis.

In a preliminary clinical study, recombinant tissue plasminogen activator (rt-PA) was injected into the anterior chamber of 18 eyes and into the vitreous cavity of 2 eyes in a total of 20 patients. The clinical indications were severe fibrin formation after filtering operations for glaucoma (8 eyes), diabetic neovascular glaucoma (3), fibrin and hemorrhage after vitrectomy (3), keratoplasty (3), posterior chamber lens implantation (1), trauma (1), and endophthalmitis (1). Complete fibrinolysis within a minimum of 2 h was achieved in 81% of 26 injections. Although doses of about 12 micrograms rt-PA were generally given, in our observations, 6 micrograms proved to be sufficient for rapid fibrinolysis in selected cases. Injections of rt-PA should not be considered before the 3rd postoperative day so as to avoid rebleeding and recurrent fibrin formation. No toxic intraocular side effect was observed after the use of rt-PA in this study.

Adult↗
PubMed1991

[Vitrectomy in secondary complications caused by intraocular foreign body].

Endophthalmitis and reduced vision as late complications of penetrating ocular injuries cause specific diagnostic problems. A persisting endopthalmitis may be caused by unnoticed organic foreign bodies (f.b.) like lashes or a splinter of glas. Endophthalmitis recurring months or years after a perforating injury indicates the possibility of a spontaneous mobilization of a f.b. Vitrectomy and removal of the f.b. is the therapy of choice in either situation. Five typical cases are presented: lashes encapsulated in the ciliary body following a limbal perforation; an intraretinal incarceration of a lash of unknown history; spontaneous dislocation of a glas splinter from the ciliary body into the anterior chamber; delayed spontaneous translocation of a 10 x 11 mm metallic f.b. from tenon's space transsclerally into the subretinal space leading to endophthalmitis one year after a severe perforating injury; secondary mobilization of an intraretinal piece of stone during a posterior hyaloid detachment. In each case, vitrectomy was performed and the f.b. removed via pars plana. Secondary surgery for retinal detachment or PVR was necessary in 2 cases. The final visual acuity was 20/20 in 3 cases and 10/20 or better in 2 cases.

Adult↗
PubMed1990

Patterns of failure following curative resection of gastric carcinoma.

To identify patterns of failure following curative resection of gastric carcinoma, the records of 130 patients undergoing resection with curative intent at the Massachusetts General Hospital were reviewed. The total local-regional failure rate was 38% (49/130 patients), with 21 patients having local-regional failure alone and 28 patients having local-regional failure and distant metastases. The incidence of local failure rose with the more advanced stages of disease. Tumors staged B2, B3, C2, and C3 had local-regional failure rates in excess of 35%. This group of patients might benefit from adjuvant radiation therapy to the tumor bed and regional lymphatics. Local-regional failure rate was highest in the anastomosis or stump 33/130 (25%), followed by the stomach bed 27/130 (21%). The overall incidence of distant metastases was 52% (67/130 patients) and rose in the more advanced disease stages. Tumors staged B2, B3, C2, and C3 had rates of distant metastases greater than 50%. Sixty-one patients (77%) had failure in the abdomen (liver, peritoneal surface, adrenal, kidney, and spleen, but excluding tumor bed, anastomosis, or regional nodes). Patients with Stage B2, B3, C2, and C3 tumors had total abdominal failure rates greater than 40%. The highest failure rates in the liver were in Stages B3 and C3, in which the subsequent development of liver metastasis was 40% and 47%, respectively. Peritoneal seeding occurred in 30/130 (23%) of patients and was highest in Stages C2 and C3, with rates of 27% and 41%, respectively.

Abdomen↗
PubMed1990

[Measuring the vascular caliber in diabetic retinopathy before and following photocoagulation].

The calibers of 4 retinal arterioles and 4 venoles of each of 58 patients with diabetic retinopathy (DR) were measured on fundus photographs before and after photocoagulation (PC). The measurements were repeated at approximately one-year intervals following photocoagulation (PC) of one eye of each patient. The mean caliber of arterioles and venoles of DR patients was 15.4% greater than in nondiabetic subjects. This finding may be interpreted as an autoregulatory response to relative tissue hypoxia. Following PC there was a significant reduction in both arterial and venous vessel caliber. In a multivariate regression analysis, the reduction in venous caliber correlated significantly with the number of coagulation spots. A weak correlation was found with arterial hypertension, change in visual acuity, and change in a calculated DR score. The reduction in pathologic vessel calibers following PC is indicative of an improvement in retinal hemodynamics. Photographic quantification of retinal vessel changes may be of prognostic value, i.e., for assessing the course of DR before and after treatment by PC.

Diabetic Retinopathy↗