Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients.

BACKGROUND: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability. METHODS: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. RESULTS: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel-carboplatin experienced less alopecia. The compound successful outcome ("no head covering" plus "who grade 0/1") was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel-cyclophosphamide or 6 cycles of paclitaxel-carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel-doxorubicin-cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil-epirubicin-cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin-cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. CONCLUSIONS: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients.

Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation.

OBJECTIVE: To test the effects of sequential exposure to FGF2, 9 and 18 on human Mesenchymal Stem Cells (hMSC) differentiation during in vitro chondrogenesis. DESIGN: Control and FGF2-expanded hMSC were cultured in aggregates in the presence of rhFGF9, rhFGF18 or rhFGFR3-specific signaling FGF variants, starting at different times during the chondroinductive program. Quantitative real time polymerase chain reaction (qRT-PCR) and immunocytochemistry were performed at different stages. The aggregate cultures were switched to a hypertrophy-inducing medium along with rhFGFs and neutralizing antibodies against FGFR1 and FGFR3. Histological/immunohistochemical/biochemical analyses were performed. RESULTS: FGF2-exposed hMSC during expansion up-regulated Sox9 suggesting an early activation of the chondrogenic machinery. FGF2, FGF9 and 18 modulated the expression profile of FGFR1 and FGFR3 in hMSC during expansion and chondrogenesis. In combination with transforming growth factor-beta (TGF-ß), FGF9 and FGF18 inhibited chondrogenesis when added at the beginning of the program (≤ d7), while exhibiting an anabolic effect when added later (≥d14), an effect mediated by FGFR3. Finally, FGFR3 signaling induced by either FGF9 or FGF18 delayed the appearance of spontaneous and induced hypertrophy-related changes. CONCLUSIONS: The stage of hMSC-dependent chondrogenesis at which the growth factors are added impacts the progression of the differentiation program: increased cell proliferation and priming (FGF2); stimulated early chondrogenic differentiation (TGF-ß, FGF9/FGF18) by shifting the chondrogenic program earlier; augmented extracellular matrix (ECM) production (FGF9/FGF18); and delayed terminal hypertrophy (FGF9/FGF18). Collectively, these factors could be used to optimize pre-implantation conditions of hMSC when used to engineer cartilage grafts.

Course of cognitive functioning during stroke rehabilitation.

The aim of the study was to determine the course of cognitive functioning within the subacute phase (< 4 months) after stroke during rehabilitation. Stroke patients admitted to a rehabilitation centre were submitted to a neuropsychological examination on admission (1 month post-stroke) and upon discharge (4 months post-stroke). Cognitive domains studied were attention, executive functioning, memory, and visual attention. Forty-two patients (mean age = 57.1 years; SD = 7.7) participated. At admission more than half of the patients showed deficits in attention and memory. Patients improved significantly on these domains; the largest improvement was seen in the domain of visual attention, while executive functioning did not improve significantly. A differential course of cognitive functioning was found in the subacute phase after stroke. The prognosis of visual attention is the most prominent.

[Life-threatening macroglossia following cleft palate palatoplasty]. / Lebensbedrohliche Makroglossie nach Gaumenspaltenverschluss.

The case of a 13-month-old child who developed a life-threatening macroglossia with airway obstruction following palatoplasty for a cleft palate is reported. As direct laryngoscopy was not feasible a laryngeal mask (LM) was inserted to secure the airway. Under fiber optic guidance an endotracheal tube was then introduced via the LM. In this article the incidence, pathophysiology, clinical dynamics, options for emergency anesthesia management and organizational implications of this rare but typical complication in the field of oral and craniomaxillofacial surgery are reported.

Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD during human epidermal keratinocyte differentiation.

Activator protein 1 (AP1) family proteins have been implicated in the regulation of genes expressed in the epidermis. However, no comprehensive analysis of the expression patterns of the known AP1 family proteins in the human epidermis or any other terminally differentiating tissue has been performed. In the present study we describe the localization of c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD in the normal human epidermis. Each is expressed in specific epidermal layers. c-fos is localized in the nuclei of the upper spinous and granular layer cells. FosB is present in the nuclei in all layers. Fra-1 is absent from the basal layer, but is present in all other layers. Fra-2 is detected in all layers, but staining intensity is increased in the upper spinous layer. c-jun staining is limited to the granular layer, while junB and junD are present in all layers. The differentiation-dependent pattern of expression of the AP1 family members suggest an important role for these proteins in specifying the temporal and spatial pattern of gene expression during keratinocyte differentiation.

Epidermal keratinocytes - genes and their regulation.

In recent years, the human epidermal keratinocyte has been extensively studied. These studies have shown that epidermal growth factor (EGF), transforming growth factor-beta (TGFbeta), retinoids, phorbol ester, vitamin D and other agents regulate keratinocyte proliferation, differentiation, apoptosis and gene expression. We review progress in understanding the mechanisms that regulate keratinocyte structural gene expression. In most cases little is known regarding the factors that regulate gene expression in response to a physiological agent. However, the available results suggest a role for a variety of transcription factors, including STAT factors, NFkappaB, octamer site (OCT) binding proteins and activator protein 1 (AP1) factors in regulating expression of these genes. Among these transcriptional regulators, AP1 appears to play a central role. We review the current literature regarding the regulation of involucrin, loricin, transglutaminase type 1 and cytokeratin gene expression. This survey indicates that the AP1 family of transcriptional regulators is implicated in the regulation of nearly all of these genes. We also discuss recent studies which describe the distribution of the AP1 factors, c-jun, junB, junD, Fra-1,Fra-2, c-fos and fosB, in epidermis.

The epidermis: genes on - genes off.

The epidermal keratinocyte stem cell is distinguished by a relatively undifferentiated phenotype and an ability to proliferate. As part of a carefully orchestrated process, the offspring of these stem cells lose the ability to proliferate and begin a process of morphologic and biochemical transformation that results in their conversion into corneocytes. This process requires the coordinated expression of a host of cellular genes. The mechanisms responsible for regulation of these genes is an area of intense interest. In keratinocytes, as in other cell types, the expression of most genes is regulated at the transcriptional level by a class of proteins called transcription factors. Transcription factors are nuclear proteins that regulate transcription by mediating the final steps in the relay of information from the cell surface to the nucleus and the gene. These factors bind to specific DNA sequence elements located within the target gene. In this brief review we summarize evidence implicating activator protein 1 (AP1), AP2, Sp1, POU domain, CCAAT enhancer binding protein, and several other transcription factors as regulators of expression of keratinocyte genes.

Involucrin--structure and role in envelope assembly.

Recent findings have revealed much about the structure of involucrin. These findings make it possible to propose specific models regarding the role of involucrin and the mechanism of its crosslinking as an envelope precursor. These models provide clearly testable hypotheses that are expected to provide additional insights into the mechanism of cornified envelope assembly.

Ticarcillin therapy of risk patients with infections due to Pseudomonas aeruginosa.

The implication of nosocomial infection due to Pseudomonas aeruginosa is demonstrated by comparing the bacteriological findings with the clinical picture of ten patients in a surgical intensive care unit. The occurrence of this organism and its resistance to beta-lactam-antibiotics and aminoglycosides is demonstrated. Ticarcillin was administered to ten patients following bacteriological and clinical evidence of infections due to P. aeruginosa. The pathogenicity of P. aeruginosa as an organism complicating the course of severely injured patients is discussed. Therapeutic consequences in regard to possible combination with other antibiotics are suggested.

[Staged lavage therapy in diffuse peritonitis]. / Etappenlavagetherapie bei diffuser Peritonitis.

Sequential lavage is introduced as a new treatment for severe diffuse purulent peritonitis. Following surgical removal of the focus and intraoperative intraabdominal lavage, the sequential lavage technique was applied with length of treatment dependent on the severity of each case. Data from 21 patients were recorded for the study. Subject lethality was 19%. Three patients survived the so-called "incurable triad".

Transcription factor regulation of epidermal keratinocyte gene expression.

The epidermis is a tissue that undergoes a very complex and tightly controlled differentiation program. The elaboration of this program is generally flawless, resulting in the production of an effective protective barrier for the organism. Many of the genes expressed during keratinocyte differentiation are expressed in a coordinate manner; this suggests that common regulatory models may emerge. The simplest model envisions a 'common regulatory element' that is possessed by all genes that are regulated together (e.g., involucrin and transglutaminase type 1). Studies to date, however, have not identified any such elements and, if anything, the available studies suggest that appropriate expression of each gene is achieved using sometime subtly and sometime grossly different mechanisms. Recent studies indicate that a variety of transcription factors (AP1, AP2, POU domain. Sp1, STAT factors) are expressed in the epidermis and, in many cases, multiple members of several families are present (e.g., AP1 and POU domain factors). The simultaneous expression of multiple members of a single transcription factor family provides numerous opportunities for complex regulation. Some studies suggest that specific members of these families interact with specific keratinocyte genes. The best studied of these families in epidermis is the AP1 family of factors. All of the known AP1 factors are expressed in epidermis [52] and each is expressed in a specific spatial pattern that suggests the potential to regulate multiple genes. It will be important to determine the role of each of these members in regulating keratinocyte gene expression. Finally, information is beginning to emerge regarding signal transduction in keratinocytes. Some of the early events in signal transduction have been identified (e.g., PLC and PKC activation, etc.) and some of the molecular targets of these pathways (e.g., AP1 transcription factors) are beginning to be identified. Eventually we can expect to elucidation of all of the steps between the interaction of the stimulating agent with its receptor and the activation of target gene expression.

[Effect of metoprolol on the circulation after head trauma. Studies during continuous intravenous administration (author's transl)]. / Kreislaufwirkung von Metoprolol bei Schädel-Hirn-Verletzten. Untersuchungen während kontinuierlicher intravenöser Applikation.

The influence of continuous intravenous administration of metoprolol on heart rate and haemodynamics was tested in ten unconscious patients who, after sustaining a head injury, developed sinus tachycardia due to increased sympathicotonia. In preliminary studies on three patients the effective dosage for heart rate reduction was determined. Following this, seven patients received 0.15 mg/kg . h of metoprolol over 36 hours. Heart rate decreased from an average of 127.5 to 78.8/min, a statistically significant reduction. Stroke volume index significantly rose from an average of 35.5 to 52.3 ml/m2, while other haemodynamic variables were not or only slightly changed. Cardiac index fell (not significantly) from 4.51 to 3.81/min . m2, peripheral vascular resistance rose (not significantly) form 942.4 to 1061.7 dyn . s . cm-5. Arterial and pulmonary artery pressures as well as filling pressures of right and left ventricle and left ventricular work index were not altered. Total oxygen consumption and oxygen extraction rate also remained unchanged. Measurement of metoprolol plasma levels in four patients excluded the possibility of a cumulative effect.

Maximal oxygen uptake during field running does not exceed that measured during treadmill exercise.

Modern ergometric equipment enables the simulation of laboratory maximal oxygen uptake (.VO(2max)) testing in the field. Therefore, it was investigated whether the improved event specificity on the track might lead to higher .VO(2max) measurements in running. Identical protocols were used on the treadmill and on the track (speed was indicated by a computer-driven flashing light system). Ambulatory measurements of gas exchange were carried out throughout both tests, which were executed in randomized order. There were no significant differences ( P=0.71) in .VO(2max) between treadmill [4.65 (0.51) ml.min(-1)] and field tests [4.63 (0.55) ml.min(-1)]. However, the test duration differed significantly ( P<0.001) by approximately 5%: treadmill 691 (39) s; field test 727 (42) s. With the exception of maximum heart rate (HR(max); significantly higher in the field with P=0.02) all criteria for the degree of effort were similar between the two tests. However, the difference in HR(max) at less than 2 beats.min(-1), was practically negligible. Submaximal measurements of oxygen uptake and minute ventilation were significantly higher on the treadmill ( P<0.001 for both parameters). In summary, field tests with incremental running protocols do not result in higher .VO(2max) measurements compared to laboratory treadmill exercise. A better running economy on the track results in higher maximal velocities and longer exercise durations being sustained. The determination of .VO(2max) is not a reasonable application for ambulatory gas exchange measurements because laboratory values are not surpassed.

[Effects of ethrane and halothane on compliance and resistance (author's transl)]. / Die Beeinflussung physiologischer Atemgrössen durch ethrane und Halothan

In young patients with healthy lungs, the effects of ethrane and halothane on compliance and resistance have been investigated. With the use of ethrane we found a dose-dependent decrease in compliance, but this decrease was statistically assured only at relatively high inhalation concentrations. The resistance of the respiratory passages remained virtually unchanged. Similar changes in compliance and resistance have also been observed with the use of halothane. The decrease in compliance induced by both anesthetic agents may be due either to interference with the surface tension of the alveolar wall, or to transitory changes in the fluid content of the pulmonary parenchyma. For the practical use of ethrane and halothane no significant differences appear to exist on the basis of their effects on compliance and resistance.

[Histologic and radioautographic studies of the human endometrium under sequential oral contraceptive conditions (author's transl)]. / Histologische und autoradiographische Untersuchungen am menschilchen Endometrium unter der 2-Phasen-Therapie mit Mestranol--Lynestrenol.

PIP: To determine the effect of the 2-phase (mestrenol-lynestrol) ovulation inhibitor on the condition and proliferative activity of the human endometrium in different phases of the cycle and after different durations of therapy, 28 females (25-48 years old) on the sequential preparation were studied during 305 cycles. 97 biopsies were examined by light microscopy for morphological changes, and DNA-synthesis was investigated by radiography. In contrast to other studies, it was concluded that the sequential therapy does not imitate the usual endometrium alterations of a normal cycle. With estrogen administration up to Day 10, a proliferating endometrium was observed without glandular secretion. With subsequent combined application of gestagen-estrogen from Day 10, retronuclear secretory vacuoles appeared. The condition resembled abortive (undatable) secretion with suppressed glands, rather than the normal situation. At the end of the cycle atrophic cells and regressive alterations were observed. With prolongation of treatment the condition remained essentially the same with no increase in atrophy. This type of endometrium is unsuitable for nidation, and a nidation-inhibiting effect of the sequential preparation is assumed. Concerning DNA synthesis, intensified DNA synthesis activity was detected in the proliferation phase in the gland and surface epithelium with a sharp decrease in the secretion phase. Thymoid incorporation was observed during all cyclic phases in the stroma.^ieng

[Pharmacokinetic investigations on the penetration of mezlocillin into the pleural fluid]. / Pharmakokinetische Untersuchungen über die Penetration von Mezlocillin in das Pleurasekret.

5 g of mezlocillin were administered by a 30 minute drip infusion to each of ten patients (mean age 59.4 years). Antibiotic concentrations in serum and pleural fluid were assayed microbiologically at regular intervals. The antibiotic concentrations determined 1.5 and 8 hours after beginning the infusion were between 83.9 and 4.0 mg/l in the serum and 53.1 and 6.5 mg/l in the pleural fluid. A comparison of the mean antibiotic concentration found in the pleural secretions (22 mg/l) with the minimal inhibitory concentrations of clinically relevant pathogens shows that mezlocillin covers 69% to 84% of the pathogen spectrum. Mezlocillin can thus be used in the therapy of infectious pleural effusions.