Kaposi's sarcoma in AIDS patients: Long-term treatment with recombinant interferon alpha-2A and chemotherapy

Summary We evaluated the response to therapy and outcome in patients with HIV-associated KS. Eighteen of 26 patients with newly diagnosed KS were treated continuously with IFN until progression of the disease occurred. In most patients with progressive disease, chemotherapy, usually with vinca alcaloid derivatives was instituted. Results were disappointing: 10 of 26 patients (38.5%) died after a median follow-up period of 4.5 months. Survival was shortest in patients who developed opportunistic infections, malignant lymphoma, or had a low OKT₄/OKT₈ ratio. Only one patient showed a complete remission and one patient had a partial remission under IFN therapy. Five additional patients had stable disease. Chemotherapy was without measurable effect on KS in patients who had progressive disease under IFN. IFN therapy was associated with various, not life-threatening adverse effects and was best tolerated by patients with a low OKT₄/OKT₈ ratio. Our results indicate that only a small portion of AIDS patients with KS seem to benefit from a continuous treatment with IFN.Abbreviations AIDS Acquired immunodeficiency syndrome - CNS Central nervous system - ELISA Enzyme linked immunosorbent assay - ESR Erythrocyte sedimentation rate - HIV Human immunodeficiency virus - IFN Recombinant interferon alpha-2a - KS Kaposi's sarcoma - WHO World Health Organization     

Patienten-Compliance

Zusammenfassung Verschiedene Untersuchungen über die Compliance oder Therapiedisziplin von Patienten haben gezeigt, daß zwischen 20 bis 50% der Patienten vor allem in der Langzeittherapie die ärztlichen Verordnungen nicht oder nur ungenügend befolgen. Die Non-Compliance ist damit seit der Einführung wirksamer Medikamente insbesondere in der Behandlung der essentiellen Hypertonie, bei Fettstoffwechselstörungen, sowie bei Patienten unter tuberkulostatischer Therapie oder prophylaktischer Chemotherapie zu einem der wichtigsten therapielimitierenden Faktoren geworden.Die Einnahmedisziplin verschlechtert sich im Laufe der Behandlung zusehends. In den ersten vier Monaten ist mit einem Abfall der Compliancerate um 30% zu rechnen, nach 5 Jahren ist nur noch ein Fünftel bis ein Viertel der Patienten therapietreu.Die Zuverlässigkeit der Patienten läßt sich mit indirekten Bestimmungsmethoden wie Patientenbefragung, Pillenzählen oder aufgrund der Therapiewirkungen abschätzen. Eine genaue Ermittlung der Compliancerate erfordert die Bestimmung der Medikamente oder Markersubstanzen im Serum oder Urin.Die Ergebnisse von Untersuchungen über compliancebestimmende Faktoren sind zum Teil widersprüchlich. Als gesichert kann hingegen gelten, daß psychische Erkrankungen insbesondere Schizophrenie, ein komplexes Therapieschema mit hoher täglicher Tablettenzahl, Therapien, welche eine Änderung von Lebensgewohnheiten erfordern, eine langdauernde Behandlung und ungenügende, schlecht organisierte Nachkontrollen mit langen Wartezeiten für den Patienten eine schlechte Therapiedisziplin zeigen. Im weiteren beeinflussen das Krankheitsbewußtsein sowie die Einstellung der Familie das Einnahmeverhalten der Patienten.Compliancefördernde Maßnahmen richten sich nach den Faktoren, welche die Therapietreue der Patienten negativ beeinflussen.Entsprechend sollte durch eine Verwendung von Slow-Release-Präparaten die tägliche Tablettenzahl möglichst klein gehalten werden. Bei mehreren Tabletteneinnahmen pro Tag ist ein schriftlicher Verordnungszettel (aide-memoire) von Nutzen. Durch regelmäßige engmaschige Nachkontrollen mit festen Terminen und kurzen Wartezeiten sollte in der Langzeittherapie die drop-out-Rate reduziert werden. Eine zusätzliche Betreuung durch paramedizinisches Personal zeigt ebenso wie der Einsatz von Therapiegruppen vor allem in der Betreuung von übergewichtigen Patienten und Hypertonikern einen günstigen Effekt auf die Compliance. Die Beteiligung des Patienten an der Behandlung und Überwachung seiner Erkrankung z.B. durch Blutdruckselbstmessung bei den wenig symptomatischen Hypertonikern führt zu einer deutlichen Verbesserung der Einnahmedisziplin. Bei Therapien, welche eine Änderung von Lebensgewohnheiten erfordern (Diät, Alkoholabstinenz, Nikotinabstinenz u.a.), sollte die Familie (Ehefrau) in den Therapieplan miteinbezogen werden.Die Patientencompliance verdient aufgrund ihrer praktischen Bedeutung (Nichterreichen des Therapieziels, Beeinflussung von Ergebnissen der Arzneimittelforschung, unnötige Kosten) eine vermehrte Beachtung im Rahmen der Patientenbetreuung. Compliancevermindernde Faktoren sollten möglichst eliminiert und Maßnahmen zur Verbesserung der Therapiedisziplin ergriffen werden.     

Retinoic acid signaling cascade in differentiating murine epidermal keratinocytes: Alterations in papilloma- and carcinoma-derived cell lines

The retinoic acid (RA) signaling pathway was investigated by transient transfection of a chloramphenicol acetyltransferase (CAT) reporter gene construct containing the RA response element (RARE) of the murine (m) RARβ2 gene into murine primary epidermal keratinocytes (PEK), papilloma-derived SP1 cells, and carcinoma-derived 3P2 cells. Murine PEK transfected in a low-Ca²⁺ medium (0.05 mM Ca²⁺) exhibited a strong transactivation of the CAT gene after exposure of the cells to 0.1 μM RA. Transactivation of the CAT gene could, however, also be achieved by shifting RAREβ2-transfected low-Ca²⁺ PEK to high-Ca²⁺ conditions (0.15–1.2 mM Ca²⁺). Concomitantly, the Ca²⁺ raise also led to the induction of both cellular retinol (ROL)-binding protein I (CRBPI) and cellular RA-binding protein II (CRABPII), whereas expression of cellular RA-binding protein I (CRABPI) was not observed. Moreover, induction of in vitro differentiation also activated the ROL→RA converting enzyme system in PEK. These findings suggest the following sequence of events involved in the high Ca²⁺–mediated activation of RAREβ2. First, high Ca²⁺ induces the synthesis of mCRBPI, which binds ROL released from retinyl ester stores and makes it accessible to the ROL→RA converting enzyme system. Enzymatically generated RA is taken over by mCRABPII and transported to the nucleus, where it acts as ligand for nuclear receptors, which complex with RAREβ2 to activate the reporter gene. This hypothetical cascade of RA signaling was supported by our findings that inhibition of the ROL→RA converting enzyme system by citral abolished the Ca²⁺-mediated transactivation of the CAT gene in a nontoxic manner. Studies in transformed murine cell lines revealed that Ca²⁺-induced activation of RAREβ2 was essentially maintained in papilloma-derived SP1 cells, although all parameters of the Ca²⁺-dependent RAREβ2 activation cascade were induced to a much lower extent. In contrast, strong RAREβ2 activity was already observed in low-Ca²⁺ carcinoma-derived 3P2 cells. Low-Ca²⁺ 3P2 cells also expressed high levels of both mCRBPI and mCRABPII and possessed a highly active ROL→RA converting enzyme system. Again, inhibition of the enzyme by citral abolished RAREβ2 activity in low-Ca²⁺ 3P2 cells. Our data show that Ca²⁺-induced differentiation in cultured murine PEK entails a series of events that ultimately lead to the activation of RARE-containing genes. These properties are maintained in transformed epidermal keratinocytes. However, with increasing malignant potential of the cells, the respective signaling pathway becomes independent from a differentiation stimulus and leads to constitutive activation of RARE-controlled genes. Mol. Carcinog. 20:58–67, 1997. © 1997 Wiley-Liss, Inc.     

Serious aortic complications in a patient with Turner syndrome

An asymptomatic young woman was discovered to have life-threatening aneurysms and dissection of the thoracic aorta during routine evaluation in a Turner syndrome (TS) study. The presence of a heart murmur and hypertension had led to diagnosis and surgical repair of an atrial septal defect at age 5 and of aortic coarctation at age 12. The diagnosis of TS was made at 16 years of age due to short stature and delayed pubertal development. She was treated with growth hormone from age 16 to 18 and with atenolol, thyroid hormone, and estrogen. She discontinued her medications and was lost to medical follow-up at age 20. Upon presenting here at age 26, she reported a very active lifestyle, including vigorous exercise and an acting career, with no symptoms of chest or back pain or shortness of breath. Cardiovascular imaging revealed aortic regurgitation, an unsuspected dissection of a severely dilated ascending aorta, and a large descending aortic aneurysm. She required surgical replacement of her aortic valve and ascending aorta, followed by endovascular repair of the descending aortic aneurysm. This patient illustrates the importance of considering the diagnosis of TS in girls with congenital aortic defects and the absolute necessity for close, expert follow-up of these patients who are at high risk for complications after surgical repair due to an underlying aortopathy, hypertension, and metabolic disorders. This patient also emphasizes the need to publicize and follow screening guidelines as there is an increasing number of patients with congenital defects who need transition to adult care.     

Localization and characterization of the interleukin 1 immunoreactive pool (IL-1 alpha and beta forms) in normal human epidermis

A panel of polyclonal antisera and monoclonal antibodies (MoAb) raised against recombinant human interleukin 1 alpha (rh IL-1 alpha) and beta (rh IL-1 beta) was used to localize IL-1 pools within epidermal compartments and to characterize the immunoreactive species. Interleukin 1 alpha and beta immunoreactive species were detected by Western blot analysis only when epidermal extracts were obtained in extraction buffers containing dithiothreitol (DTT), sodium dodecyl sulfate (SDS), or 2 mercaptoethanol. Together with the 31-kD (intracellular precursor molecule) and the 17-kD (mature, secreted form) species, most of the antisera and MoAb reacted with a protein of 52-kD that was not found in several internal organs, and from which a 31-kD form could be released upon reelectrophoresis. Interleukin 1 beta immunoreactivity was consistently found by immunohistology at the level of the stratum granulosum, where IL-1 alpha immunoreactivity, although less consistently, also localized. Several monoclonal antibodies to IL-1 beta reacted intensively and specifically with epidermal basal cells. At the electron microscopical level, IL-1 beta immunoreactivity was detected in the upper layers of the stratum granulosum; it appeared to be membrane associated and suggested an exocytosis process similar to that involving lamellar bodies. These observations 1) confirm the presence of IL-1 species in the normal unstimulated human epidermis, 2) show that both IL-1 alpha and beta are detectable herein, 3) identify 52-kD IL-1 alpha and beta immunoreactive bands that appear special to the epidermis, and 4) suggest a link between epidermal IL-1 and the differentiation process of the keratinocyte.     

Retrospective Analysis of Emotional Burden and the Need for Support of Patients and Their Informal Caregivers after Palliative Radiation Treatment for Brain Metastases

Cancer burdens not only the patients themselves but also their personal environment. A few studies have already focused on the mental health and personal needs of caregivers of patients. The purpose of this retrospective analysis was to further assess the emotional burden and unmet needs for support of caregivers in a population of brain metastasis patients. In the time period 2013–2020, we identified 42 informal caregivers of their respective patients after palliative radiation treatment for brain metastases. The caregivers completed two standardized questionnaires about different treatment aspects, their emotional burden, and unmet needs for support. Involvement of psycho-oncology and palliative care was examined in a chart review. The majority of the caregivers (71.4%, n = 30) suffered from high emotional burden during cancer treatment of their relatives and showed unmet needs for emotional and psychosocial support, mostly referring to information needs and the involvement in the patient’s treatment decisions. Other unmet needs referred to handling personal needs and fears of dealing with the sick cancer patient in terms of practical care tasks and appropriate communication. Palliative care was involved in 30 cases and psycho-oncology in 12 cases. There is a high need for emotional and psychosocial support in informal caregivers of cancer patients. There might still be room for an improvement of psychosocial and psycho-oncological support. Care planning should cater to the emotional burden and unmet needs of informal caregivers as well. Further prospective studies in larger samples should be performed in order to confirm this analysis.