Frequent administration of Dabis Maleate, a phase I study.

Dabis Maleate (1,4-bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1] Heptane dihydrogen dimaleate) (NSC 262666) is an alkylating quaternary nitrogen compound. In a previous phase I study using a once-every-3-weeks administration the dose-limiting toxicity was neurotoxicity and the recommended dose for phase II studies was 750 mg/m2 iv every 3 weeks. In vitro studies suggested a higher activity after more frequent administration, and in vivo studies a better therapeutic index with prolonged infusion. We studied 11 patients with solid tumors. Dose levels tested ranged from 250-750 mg/m2, either as a day 1-3 regimen or weekly, the latter as bolus administration or as prolonged infusion. The dose-limiting toxicity was neurotoxicity consisting of paresthesias and ataxia. Nausea and vomiting were moderate. No other major toxicity was observed. The dose recommended for phase II studies is 500 mg/m2/week as a 6-hour iv infusion for 6 weeks, followed by a 3-week rest period.     

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours.

Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies.     

Cerebrospinal fluid neuron-specific enolase is reduced in Alzheimer's disease

Neuron-specific enolase (NSE), a glycolytic enzyme enolase found in brain, was examined in the cerebrospinal fluid and serum of 30 patients with presumptive Alzheimer's disease (AD) and of 13 healthy controls and evaluated as a measure of neuronal functional activity associated with AD. The cerebrospinal fluid NSE levels of patients with AD were significantly reduced and serum NSE levels were significantly increased from controls. Cerebrospinal fluid NSE levels may be representative of central nervous system cell loss or a decrease in neuronal functional activity associated with AD.     

Identification and characterization of a rat protein (p 105) auto-antigenic in rats bearing a progressive syngeneic colon carcinoma.

Sera from BDIX rats inoculated with 2 tumor clones derived from a single syngeneic colon carcinoma were assayed by Western blotting for the presence of antibodies against the grafted tumor. The PROb clone is progressive and produces metastases. We observed that rats bearing this tumor developed antibodies against an unglycosylated water-soluble protein of 105 kDa. The magnitude of this humoral response, as assessed by the intensity of the signal on immunoblots, was inversely correlated with survival of the rats. Furthermore, rats inoculated with the REGb clone, which is immunologically rejected, never developed detectable antibodies against the tumor. Antisera from rats injected with PROb tumor detected p105 antigen in cellular extracts from the REGb clone and from a series of rat and human cell lines. This protein was also detected in variable amounts in some normal adult and fetal tissues. Treatment of PROb or REGb cells by either interferon-gamma or heat shock did not significantly alter the expression of the p105 auto-antigen.     

Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.     

Bündelhaar-Follikulitis

Zusammenfassung Bei der Bündelhaar-Follikulitis (tufted hair folliculitis) handelt es sich um eine durch Staphylococcus aureus verursachte, chronisch entzündliche und vernarbende Haarbodenerkrankung, die charakterisiert ist durch das umschriebene Auftreten von Bündelhaaren. Histopathologisch findet sich eine perifollikul?re Entzündung im oberen Bereich der Haarfollikel unter Aussparung der tiefen Follikelanteile. Innerhalb der Entzündungsareale münden mehrere Haare aus getrennten Haarwurzeln in ein gemeinsames Infundibulum mit dilatiertem Ostium. Das Krankheitsbild ist als eine Erscheinungsform der Folliculitis decalvans capillitii Quinquaud anzusehen, bei der die Auffassung besteht, da? die Infektion mit Staphylococcus aureus den pathogenetischen Initialfaktor darstellt, und Besonderheiten der Follikelanatomie und Immunantwort die individuelle Morphologie bestimmen: Dabei ist anzunehmen, da? die Ausbildung fl?chig atropher Narben mit vollst?ndigem Untergang der Hautanhangsgebilde (im Falle der Folliculitis decalvans) oder das Auftreten von Haarbündeln (im Falle der Bündelhaar-Follikulitis) von der Tiefe und dem Destruktions-Potential des Entzündungsinfiltrates abh?ngen. Die Behandlung der Bündelhaar-Follikulitis ist nicht ganz unproblematisch: Die prolongierte und wiederholte Gabe staphylokokken-wiksamer Antibiotika vermag den Krankheitsverlauf zu stabilisieren. Bereits vorhandene Haarbündel mit einer besonders hohen Rezidivneigung sollten aber – wie im vorgestellten Fall – nach M?glichkeit chirurgisch exzidiert werden.

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Summary A case of tufted hair folliculutis presenting as circumscribed, tender and inflamed areas in the occiput with residual tufted follicles in a 28-year old man is reported. Tufted hair folliculitis is a characteristic localized scarring bacterial folliculitis of the scalp due to Staphylococcus aureus. Histopathological studies reveal perifollicular inflammation around the upper portions of the follicles sparing the hair root level. Within areas of inflammation, several follicles converge toward a common follicular duct with a widely dilated opening. Currently, tufted hair folliculitis is considered a variant of folliculitis decalvans of Quinquaud. Staphylococcal infection is believed to be an initial causative factor, and underlying differences in follicular anatomy or host response may be important in determining which reaction pattern occurs in an affected individual. The development of atrophy with loss of adnexal structures (in folliculitis decalvans) or of hair tufts (in tufting folliculitis) may depend upon the depth and destructive potential of the inflammatory process. The therapeutic approach is problematic; prolonged treatment with oral antibiotics may stabilize the disease, but good and at times more definitive results (as in the presented case) have been reported after radical surgical excision of the involved areas.

Eingegangen am 2. April 1996 Angenommen am 7. Juni 1996     

Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the endometrium

Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the endometrium is described. This is the first reported case of a gynecologic cancer in which the paraneoplastic syndrome has been conclusively shown by immunohistochemical analysis to be due to ectopic parathormone.