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.     

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.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

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     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

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.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.