Treatment of Kaposi's sarcoma and thrombocytopenia with vincristine in patients with the acquired immunodeficiency syndrome

Kaposi's sarcoma occurs in about one third of patients with the acquired immunodeficiency syndrome. Although in some patients the tumor is principally a cosmetic problem, other patients have progressive disease with significant morbidity. Twenty-three patients with Kaposi's sarcoma related to the acquired immunodeficiency syndrome were treated with vincristine. Three patients had a coexisting immune thrombocytopenia. Of the 18 patients evaluable for response, 11 had a partial response and 7 had a minor response. The median duration of partial response was 4 + months. All 3 thrombocytopenic patients developed a significant increase in platelet count, which in 2 was sustained with continued treatment for 6 and 9 months, respectively. We conclude that vincristine has antitumor activity in the epidemic form of Kaposi's sarcoma and that it is also effective in the treatment of associated immune thrombocytopenia.     

The importance of hemorrhage in the relationship between gross morphologic characteristics and cerebral symptoms in 376 carotid artery plaques.

In a prospective study 376 carotid artery plaques (275 symptomatic, 101 asymptomatic) were obtained from endarterectomies (184 unilateral and 96 bilateral) in 280 patients. The gross morphologic features of each plaque were noted at surgery and, together with the patient's clinical history, stored in computer memory. These data were analyzed in order to investigate the relationship of gross morphologic plaque characteristics with both the presence of cerebral symptoms and the degree of stenosis associated with the plaque. Ulceration was the most frequently observed of the five major gross plaque morphologic characteristics (46.0% of all plaques), but only intramural hemorrhage (30.6% of all plaques) was significantly more common in all symptomatic compared with all asymptomatic plaques (p less than 0.02). Hemorrhage was also the only gross characteristic significantly more common in focal symptomatic plaques when compared with either asymptomatic plaques (p less than 0.05) or nonfocal symptomatic plaques (p less than 0.01). When all the plaques were divided into three broad degrees of stenosis groups (0-39%, 40-69%, 70-99%) on the basis of angiographic data, only hemorrhage showed a significant correlation in incidence with increased degree of plaque stenosis, both when all plaques were considered (p less than 0.001) and when only symptomatic plaques were examined (p less than 0.001). The results indicate that intramural hemorrhage is the only carotid plaque gross morphologic characteristic significantly more frequent in symptomatic compared with asymptomatic plaques and the only characteristic significantly correlated with increased plaque size. These findings indicate that factors other than plaque ulceration and intraluminal thrombus play an important role in carotid plaque related cerebral symptoms. The data also raise questions concerning the unequivocal value of anticoagulant therapy in carotid artery disease, especially in highly stenotic lesions.     

Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites

Twenty-one patients were entered into a phase I trial to evaluate toxicity, antitumor effects, and biological responses at tumor sites during treatment of R24, an immunoglobulin G3 (IgG3) mouse monoclonal antibody (mAb) against GD3 ganglioside. Toxicity was related to dose of R24. Urticaria and pruritus were the most prominent side effects, with nausea, vomiting, and diarrhea occurring at the highest dose levels. Partial responses were observed in four patients lasting from 6 to 46 weeks, and mixed responses were seen in two patients. Responses occurred as early as 4 weeks and as late as 10 weeks after beginning treatment. Twenty of the 21 patients developed human IgG antibodies against R24. Antimouse Ig antibodies were first detected at a median of 14 days after starting treatment, but three of the four patients who had a partial response developed the antimouse Ig responses later than 20 days. Peak serum levels of R24 were related to dose and ranged from a mean of 0.9 micrograms/mL at the lowest dose level (1 mg/m2/d) to 44 micrograms/mL at the highest dose (50 mg/m2/d). The amount of R24 reaching tumor sites corresponded to the dose administered, and R24 could be detected in tumors as late as 30 days after finishing treatment. Inflammation at tumor sites was observed during treatment. Biopsies of tumors taken before, during, and after treatment revealed that R24 induced deposition of complement components, increased numbers of mast cells with mast cell degranulation, and infiltration of T lymphocytes. These results suggest that treatment with R24 can produce a localized inflammatory response at tumor sites that is capable of producing tumor regression.     

Quetiapine treatment of psychosis associated with dementia: a double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety, and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning. METHOD: The authors conducted a multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed quetiapine and haloperidol. Primary outcomes were change in total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors, Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS). RESULTS: Two hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4% completed; and mean Mini-Mental State Examination score was 12.8. Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No differential benefit was seen on any psychosis measure. BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo. No NPI factors showed change, including the agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was most prevalent in the haloperidol group; other safety and tolerability measures differed little among groups. CONCLUSION: All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed. Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation. Tolerability was better with quetiapine compared with haloperidol.     

Scintigraphic presentation of hip joint synovial chondromatosis

A case of hip joint synovial chondromatosis with an unusual scintigraphic pattern is described. This pattern was suggestive of a hip joint destructive reactive articular process or late manifestations of avascular necrosis of the femoral head. Concurrent radiographs were normal, as were laboratory investigations. Follow-up radiographs six months later showed radiolucencies and erosive bone changes in the diseased joint. Surgical and histopathological findings revealed well developed hip synovial chondromatosis (HSC) with thickened synovium and large, loose, cartilaginous bodies occupying and widening the tightened joint space, with destructive secondary juxta articular pressure and bone erosions. This and other scintigraphic patterns in HSC, and the differential diagnosis of the findings in patients with painful hip presentations are discussed.     

An atypical Hallermann-Streiff syndrome. Focus on dental care and differential diagnosis.

The Hallermann-Streiff syndrome (HSS) is a rare congenital disorder characterized by dyscephaly, birdlike facies, hypoplastic mandible, congenital cataracts, microphthalmia, hypotrichosis, skin atrophy, proportionate short stature, and dental anomalies. A case of a 29-year-old man with atypical HSS with neither cataracts, hair and skin alterations, nor short stature is reported, with special consideration to oral findings and dental management. Dental extractions, scaling, restorations, and endodontics were performed under local anesthesia. Later, orthodontic rehabilitation with fixed brackets was carried out. Finally, a removable partial denture for the maxillary arch was designed using transparent acrylic, and this also served as a retention splint. Young patients with HSS and other similar syndromes must be involved in personalized oral health prevention programs as early as possible. Despite numerous systemic anomalies, some of these patients may undergo conventional dental procedures under local anesthesia in the dental office.     

Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Given the purported role of the NMDA receptor in long-term potentiation, the primary purpose of the present study was to further understand the dose-related effects of ketamine on memory. The study was also designed to provide information about the relative effects of ketamine on memory versus nonmemory effects and to more fully characterize ketamine's overall pattern and time course of effects. Single intramuscular injections of ketamine (0.2 mg/kg, 0.4 mg/kg) were administered to 18 healthy adult volunteers using a double-blind, placebo-controlled, crossover design. Word lists were used to evaluate episodic memory (free recall, recognition memory, source memory) and metamemory. Working memory, time estimation, psychomotor performance, and subjective effects were assessed repeatedly for 5 hours after drug administration. Ketamine selectively impaired encoding (as measured by free recall) while sparing retrieval, working memory while sparing attention, and digit symbol substitution task speed while sparing accuracy. Ketamine did not significantly impair recognition or source memory, metamemory, or time estimation. There were no hallucinations or increases in mystical experiences with ketamine. Memory measures were less sensitive to ketamine effects than subjective or psychomotor measures. Subjective effects lasted longer than memory and most psychomotor impairments. Ketamine produces selective, transient, dose- and time-related effects. In conjunction with previous studies of drugs with different mechanisms of actions, the observed selectivity of effects enhances the understanding of the pharmacological mechanisms underlying memory, attention, psychomotor performance, and subjective experience.     

Administration of pemetrexed immediately following gemcitabine as front-line therapy in advanced non-small cell lung cancer: a phase II trial

BACKGROUND: Pemetrexed and gemcitabine have demonstrated independent anti-tumor activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The combination of these two therapies may produce synergistic anti-tumor effects. Previous studies of this combination have included a 90-min separation between the two drugs. More recent preclinical studies have suggested that this delay in administration might be unnecessary. This phase II study was designed to determine the objective tumor response rate and toxicity when pemetrexed was administered immediately after gemcitabine on day 1. METHODS: Chemona?ve patients stage IIIB with pleural effusion or stage IV NSCLC were enrolled. Treatment consisted of gemcitabine 1250 mg/m2 (30-min intravenous infusion on days 1 and 8) and pemetrexed 500 mg/m2 (10-min i.v. infusion, immediately following gemcitabine, on day 1) every 21 days. All patients received folic acid, vitamin B12, and steroid prophylaxis. RESULTS: The 53 enrolled patients completed a total of 199 cycles (median=4.0, mean=3.8). Best tumor response consisted of 1 complete response (2.0%), 15 partial responses (30.6%), 17 with stable disease (34.7%), and 16 with progressive disease (32.7%). Median time to disease progression was 3.3 months and median survival was 10.3 months. Grades 3/4 hematologic toxicities (% patients) consisted of: neutropenia (43.4), anemia (9.4), febrile neutropenia (7.5%) and thrombocytopenia (1.9). The most common grades 3 or 4 non-hematologic events were: dyspnea (15.1), fatigue (11.3), and pyrexia (9.4). One patient (1.9%) experienced grade 2 alopecia. CONCLUSION: This schedule of pemetrexed plus gemcitabine is tolerable and offered the advantage of not requiring a 90-min delay between the two drugs. Response rate, survival, time to disease progression, and toxicity were acceptable and similar to other NSCLC regimens.