Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET - randomised controlled trial.

BACKGROUND: We evaluated whether performing contrast-enhanced breast MRI in addition to mammography and/or ultrasound in patients with nonpalpable suspicious breast lesions improves breast cancer management. METHODS: The MONET - study (MR mammography of nonpalpable breast tumours) is a randomised controlled trial in patients with a nonpalpable BIRADS 3-5 lesion. Patients were randomly assigned to receive routine medical care, including mammography, ultrasound and lesion sampling by large core needle biopsy or additional MRI preceding biopsy. Patients with cancer were referred for surgery. Primary end-point was the rate of additional surgical procedures (re-excisions and conversion to mastectomy) in patients with a nonpalpable breast cancer. FINDINGS: Four hundred and eighteen patients were randomised, 207 patients were allocated to MRI, and 211 patients to the control group. In the MRI group 74 patients had 83 malignant lesions, compared to 75 patients with 80 malignant lesions in the control group. The primary breast conserving surgery (BCS) rate was similar in both groups; 68% in the MRI group versus 66% in the control group. The number of re-excisions performed because of positive resection margins after primary BCS was increased in the MRI group; 18/53 (34%) patients in the MRI group versus 6/50 (12%) in the control group (p=0.008). The number of conversions to mastectomy did not differ significantly between groups. Overall, the rate of an additional surgical intervention (BCS and mastectomy combined) after initial breast conserving surgery was 24/53 (45%) in the MRI group versus 14/50 (28%) in the control group (p=0.069). INTERPRETATION: Addition of MRI to routine clinical care in patients with nonpalpable breast cancer was paradoxically associated with an increased re-excision rate. Breast MRI should not be used routinely for preoperative work-up of patients with nonpalpable breast cancer.

Prevention of futile sentinel node procedures in breast cancer: ultrasonography of the axilla and fine-needle aspiration cytology are obligatory.

AIMS: To determine the value of ultrasonography (US) and fine-needle aspiration (FNA) of the axilla in preventing futile sentinel node procedures (SNP) in breast cancer. METHODS: Between July 2004 and June 2005, 209 female patients were evaluated and treated in our clinic for histologically proven breast carcinoma. We analysed the results of axillary staging by US and FNA retrospectively. Furthermore, we correlated the histopathologic outcome of operative procedures with the preoperative findings during examination of the axilla. RESULTS: Of the 209 patients, 195 underwent US of the axilla. In 67 patients, US was followed by FNA because of suspect lymph nodes in the axilla. Ninety-three of these 195 patients had axillary metastases. In 52 of these 93 patients, the metastases were detected prior to surgery, so that these 52 patients could be scheduled immediately for axillary lymph node dissection (ALND) and a futile SNP could be prevented. US/FNA yielded false-negative results in 41 cases, 13 of which had only a micrometastasis. CONCLUSIONS: By preoperative US and FNA of the axilla in patients with breast cancer, half of the axillary metastases can be detected prior to surgery. In more than a quarter of breast cancer patients, a futile SNP can be prevented. Therefore, preoperative US of the axilla plus FNA are obligatory in patients with breast carcinoma.

Bilateral axillary metastases of occult breast carcinoma: report of a case with a review of the literature.

The case of a 47-year-old premenopausal woman is presented in whom axillary lymph node metastases occurred on both sides 3 years apart although no primary tumor was detectable in either breast is presented. An overview of the literature on this rare entity is given. Patients with occult breast carcinoma with axillary lymph node metastases should have a complete physical examination, radiologic analysis (mammography, ultrasonography, and MRI of both breasts) and screening for disseminated disease. If there is no evidence of a primary tumor and metastases other than in the axilla, an axillary dissection should be carried out. In addition, the patient should be offered the choice of irradiation of the breast or mastectomy. Postoperatively, patients should receive appropriate systemic therapy tailored to their age, menopausal status, and receptor status.

Osmolality and solute composition are strong regulators of AQP2 expression in renal principal cells.

The water permeability of the renal collecting duct is regulated by the insertion of aquaporin-2 (AQP2) into the apical plasma membrane of epithelial (principal) cells. Using primary cultured epithelial cells from the inner medulla of rat kidney (IMCD cells), we show that osmolality and solute composition are potent regulators of AQP2 mRNA and protein synthesis, as well as the classical cAMP-dependent pathway, but do not affect the arginine vasopressin-induced AQP2 shuttle. In the presence of the cAMP analog dibutyryl cAMP (DBcAMP, 500 microM), NaCl and sorbitol, but not urea, evoked a robust increase of AQP2 expression in IMCD cells, with NaCl being far more potent than sorbitol. cAMP-responsive element-binding protein phosphorylation increased with DBcAMP concentrations but was not altered by changes in osmolality. In the rat and human AQP2 promoter, we identified a putative tonicity-responsive element. We conclude that, in addition to the arginine vasopressin/cAMP-signaling cascade, a further pathway activated by elevated effective osmolality (tonicity) is crucial for the expression of AQP2 in IMCD cells, and we suggest that the effect is mediated via the tonicity-responsive element.

Alkyl-substituted amino acid amides and analogous di- and triamines: new non-peptide G protein activators.

Synthesis and pharmacological properties of new potent direct activators of heterotrimeric G proteins are described. Compounds were synthesized from protected amino acids with alkylamines using coupling reagents (CDI, DCC, and EDC). Alkyl-substituted amino acid amides and their corresponding di- and triamines were subjected to structure-activity analysis. All compounds activated membrane-bound HL-60 GTPases in a pertussis toxin-sensitive fashion. This suggests a specific effect of compounds on the carboxy terminus of a defined subclass of heterotrimeric G proteins, i.e., members of the G alpha i subfamily. Elongation of the alkyl chain and increasing the number of amino groups enhanced the potency of compounds on HL-60 membrane-bound GTPase. N-(2,5-Diaminopentyl)dodecylamine (21) was selected to study its mode of action employing purified pertussis toxin-sensitive G proteins. It stimulated G alpha subunits by inducing the release of bound GDP. In contrast to receptors G beta gamma complexes were not required for 21-mediated activation of G alpha. Moderate isoform selectivity of its action was observed within a group of highly homologous members of the Gi subfamily with G alpha o1 being activated at lowest concentrations, whereas higher concentrations were necessary for the stimulation of G alpha i1 or transducin. We conclude that these compounds represent important tools for studying G protein-dependent cellular functions.

Separation of extracts from biological tissues into polycyclic aromatic hydrocarbon, polychlorinated biphenyl and polychlorinated dibenzo-p-dioxin/polychlorinated dibenzofuran fractions prior to analysis.

A low-pressure liquid chromatography method is presented for separating polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs) from biological tissue extracts. After removing lipid from extracts, the PAHs are separated from PCBs and PCDDs/PCDFs on a deactivated 13-24 microns silica gel column. The PCBs are subsequently separated from PCDDs/PCDFs by collecting the first fraction from an automated three column cleanup procedure for PCDDs/PCDFs. The complete method has been used to obtain high recoveries of the three compound classes for analysis by GC-electron capture detection (PCBs) or GC-MS (PAHs and PCDDs/PCDFs).

The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapment.

OBJECTIVE: The authors determined the prevalence of incisional hernia and nerve entrapment in patients with a low transverse Pfannenstiel incision. SUMMARY BACKGROUND DATA: The literature on the Pfannenstiel incision suggests an incisional hernia rate of 0.0% to 0.5%. However, in these series, physical examination, which is essential in the authors' view, was not performed. To the authors' knowledge, the prevalence of nerve entrapment after the Pfannenstiel incision is not known or has never been published. METHODS: All adult women, operated on between 1986 and 1992 using a Pfannenstiel incision and not having had another lower abdominal incision other than for laparoscopy, were invited for follow-up at the outpatient department. All patients were interviewed and subjected to a physical examination, with special interest to the presence of incisional hernia or nerve entrapment. RESULTS: In patients having had a Pfannenstiel incision, no incisional hernias were found. In patients also having had a laparoscopy, the incisional hernia rate was 3.5%. Nerve entrapment was found in 3.7%. The length of the incision was identified as a risk factor (p = 0.02). CONCLUSIONS: Incisional hernia is a rare complication of the Pfannenstiel incision. Complications of nerve damage, however, are not uncommon and should be recognized. When possible, nerves should be identified and preserved, especially when extending the incision more laterally.

Crystals of intact elongation factor Tu from Thermus thermophilus diffracting to high resolution.

The intact elongation factor Tu from the extreme thermophile Thermus thermophilus has been crystallized as a complex with the GTP analogue guanosine-5'-(beta,gamma-imido)triphosphate. The crystals are very stable in the X-ray beam and diffract to 1.9 A resolution. They exhibit space group C2, with a = 150.3(6) A, b = 99.6(3) A, c = 40.1(1) A, beta = 95.4(2) degrees, and contain one elongation factor Tu molecule per asymmetric unit.

Walker-Warburg syndrome. Case report and literature review.

The Walker-Warburg syndrome (WWS) is a fatal dysmorphic disorder of unknown etiology, but strongly suggests an autosomal recessive mode of inheritance. It is characterized by severe congenital oculo-cerebral malformations (lissencephaly, congenital hydrocephalus, and ocular lesions). The authors report a case of WWS that occurred in a consanguineous union, with a review of the literature. Possible pathogenesis, and disorders sharing the features of WWS are discussed. Families-at-risk for WWS should be identified for prenatal diagnosis and for genetic counselling.

Crystallization of blood coagulation factor XIII by an automated procedure.

Both recombinant blood coagulation factor XIII alpha-chain and factor XIII isolated from human placenta have been crystallized using a novel robotic system for the automatic screening of crystallization conditions. The monoclinic and orthorhombic crystals obtained are suitable for X-ray analysis.

Tracking multiple independent targets: evidence for a parallel tracking mechanism.

There is considerable evidence that visual attention is concentrated at a single locus in the visual field, and that this locus can be moved independent of eye movements. Two studies are reported which suggest that, while certain aspects of attention require that locations be scanned serially, at least one operation may be carried out in parallel across several independent loci in the visual field. That is the operation of indexing features and tracking their identity. The studies show that: (a) subjects are able to track a subset of up to 5 objects in a field of 10 identical randomly-moving objects in order to distinguish a change in a target from a change in a distractor; and (b) when the speed and distance parameters of the display are designed so that, on the basis of some very conservative assumptions about the speed of attention movement and encoding times, the predicted performance of a serial scanning and updating algorithm would not exceed about 40% accuracy, subjects still manage to do the task with 87% accuracy. These findings are discussed in relation to an earlier, and independently motivated model of feature-binding--called the FINST model--which posits a primitive identity maintenance mechanism that indexes and tracks a limited number of visual objects in parallel. These indexes are hypothesized to serve the function of binding visual features prior to subsequent pattern recognition.

Ophthalmologic findings in the fragile X syndrome.

The fragile X (Fra[X]) syndrome is a commonly encountered X-linked recessive chromosomal disorder associated with mental retardation that primarily affects males. The demonstration of a fragile site in the long arm of the X chromosome (Xq27-28) through special culture techniques confirms the diagnosis. Phenotypic features are often lacking, especially in early life. We studied the ophthalmologic and clinical characteristics of 15 patients (13 male and two female) with the Fra(X) syndrome and reviewed the clinical picture of the disorder. Strabismus was the most prevalent ophthalmologic abnormality and was observed in six patients. The frequent occurrence of strabismus in our series suggests that it is a commonly associated abnormality. It is recommended that the Fra(X) syndrome be added to the list of genetic and dysmorphic disorders with which strabismus is frequently associated.

Bilateral optic nerve aplasia associated with hydranencephaly.

A case of bilateral optic nerve aplasia (ONA) associated with hydranencephaly and other multiple congenital anomalies in an infant is reported. Its occurrence in an offspring of a consanguineous union may implicate an autosomal recessive transmission. A brief review of ocular embryology is presented in relation to the possible pathogenesis of bilateral ONA. Bilateral ONA is most likely to be due to failure of the retinal ganglion cells to develop, consequently, the optic disc and nerve, and the retinal blood vessels are absent. Bilateral ONA is rare, and is associated with major CNS anomalies, and with other multiple, often severe congenital malformations. Bilateral ONA appears to be a distinct entity, independent from its unilateral counterpart and can be adequately diagnosed on clinical grounds.

[Counseling on contraception following interruption of pregnancy. Responsibility of the hospital gynecologist. Model of contraceptive counseling at the Gynecological Clinic Berlin-Neukölln]. / Kontrazeptionsberatung nach Schwangerschaftsabbruch. Eine AUfgabe des klinisch tätigen Frauenarztes. Das Modell der Kontrazeptionsberatung an der Frauenklinik Berlin-Neukölln.

PIP: Providing counseling concerning methods of contraception is the responsibility of the hospital gynecologist during the immediate postabortion period. It is during this period that patients prove unexpectedly receptive to contraception instruction. Form and contents of this instruction as practiced at the School of Contraception of the Frauenklinik Berlin-Neukolln are described. (author's modified)^ieng

Small-group training as an alternative to individual programs for profoundly retarded persons.

A comparison of group and individualized training methods was made by teaching 12 profoundly retarded men a series of imitative tasks under one of three program conditions. Each of the conditions was allotted 20 hours of training time from staff. The four members of the intact-group program received their 20 hours of instruction on a group basis. The four individual-program members had the training time divided between them and were taught separately. In a third program, the add-in group had the entry times of its membership staggered so that special attention could be given to each new member. The results indicated that the group programs were as effective as individual treatment for increasing imitative skills when staff time was held constant. Advantages of group programming were discussed in terms of increased activity and socialization for clients.

Effects of error and errorless discrimination acquisition on reversal learning.

The effectiveness of trial-and-error, graded-choice, and verbal-instruction procedures on the acquisition and maintenance of a two-choice simultaneous color discrimination in an intradimensional double-reversal learning situation was studied using 18 first-grade children. After acquiring a red-green discrimination during one 70-trial session, the discriminative roles of the stimuli were reversed for 30 trials, followed by a second reversal for 30 trials. Children in the graded-choice and verbal-instruction groups acquired and maintained the discriminations with fewer errors than children who learned by trial and error. The importance of the results in terms of two-stage discrimination learning theories is pointed out and similarities between errorless learning and overtraining are discussed.

Application of a graded choice procedure to obtain errorless learning in children.

A simultaneous, two-choice color discrimination was carried out with three groups of four- to seven-year-old children. For Groups I and II, the opportunity to respond to the incorrect stimulus was controlled (graded) over three different conditions. First, only a red light (S+) and its retractable bar were presented (16 trials for Group I and 316 trials for Group II). Second, a green light (S-) was added with its correlated bar retracted for 14 trials. Third, 40 trials were given with both stimuli on and their correlated retractable bars extended. The opportunity to respond to S- was not graded for Group III children. They experienced only the third condition applied to Groups I and II. Responses to S+ were reinforced for all three groups, while responses to S- were not. Children in the first two groups made from zero to three responses to S-, while the control children emitted 11 to 46 errors. The results demonstrate that fading in S- or presenting S- early in the training procedure are sufficient, but not necessary conditions for errorless learning.