Evaluation of CHIP (iproplatin) in recurrent pediatric malignant solid tumors

CHIP (325 mg/M²), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE=7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.     

Effects of chain-length and unsaturation on affinity and selectivity at muscarinic receptors.

1. Lengthening the chain in diphenylacetylcholine decreases affinity for muscarinic cholinoceptors in guinea-pig ileum. Diphenylacetoxypropyldimethylamine and its quaternary trimethylammonium salt are roughly equiactive: the dimethylamine and the piperidine have some selectivity for ileum compared with atria, but are not as active nor as selective as 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide (MeBr). With the weaker diphenylacetoxybutyl compounds the base is more active than the quaternary salt. 2. The diphenylacetoxybutyl-, cis-butenyl and trans-butenyl compounds have similar affinities. The quaternary salts are less active than the tertiary bases, but they are less selective than the butynyl analogues studied in earlier work. 3. 1,1-Diphenyl-1-hydroxy-2,4-hexadiynyl dimethylamine and its trimethylammonium salt are inactive in concentrations below 100 microM, as are the (+)-camphor-sulphonyl ester of 4-hydroxy-N-methyl piperidine and its methiodide. The (+/-)-phenylcyclopentylacetyl ester of 4-hydroxy-N-methylpiperidine methobromide is more active than its cyclohexyl analogue and than 4-DAMP MeBr but it is less selective than 4-DAMP MeBr. 4. The high selectivity of p-fluoro-hexahydrosila-diphenidol is confirmed but this compound has relatively low affinity (for ileum log K = 7.8). 5. The results indicate steric constraints to binding at muscarinic receptors which could be used to check molecular modelling of the receptor based on its known amino acid sequence. The group binding the charged nitrogen is probably at the mouth of a cavity which can accommodate two large rings (as in 4-DAMP MeBr) but with a depth less than about 7 A so that the rod-like hexadiynes cannot fit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic sonography of the fetal genitourinary tract

Fetal diagnosis has vastly improved over the last decade. Ultrasound has become the imaging modality of choice. As real-time equipment has improved technologically, the ability to deduce subtle abnormalities has greatly increased. The fetal genitourinary tract may be evaluated for renal dysplasias, anomalies, or obstruction. Points of obstruction and, at times, the exact cause of obstruction may be deduced. Abnormalities of the ureter, bladder, urethra, scrotum, or reproductive system can be detected.     

Quality of life and Kaposi sarcoma: using preference techniques to value the health gains from treatment

The goal of this work was to investigate preference techniques to value potential health gains from treatments of Kaposi sarcoma (KS). The study was designed to take the form of face-to-face interviews with a sample of men with a history of HIV/AIDS ( n=15) or HIV/AIDS and KS ( n=17). The main outcome measure was quality of life (QoL) associated with various KS disease states expressed on a scale from 0 (death) to 1 (perfect health), obtained though time trade-off (TTO) and rating scale techniques. For cutaneous lesions only, the mean TTO preference score value was 0.27. In other words, the men were willing to trade a life expectancy of 5 years for a shorter period (1.4 years) in perfect health. More severe KS health states were rated lower (0.07-0.09). The mean rating scale value for cutaneous lesions only was 0.11 and ranged from -0.10 to -0.04 for the more severe conditions; these values were systematically lower than the TTO ( P=0.014). A large overall potential gain in QoL from treatment (partial response minus stable disease) was found for each condition to be reflected in both the TTO (from 0.31 to 0.55) and the rating scale (from 0.38 to 0.44). Respondents associate KS health states with extremely poor QoL and indicate that large gains are possible through modest treatment effects. While TTO returns higher values than the rating scale, potential gains from treatments were similar. The techniques appear to be suitable for application to QoL and economic evaluation of treatments of KS.     

Blastomycosis of the eyelid and conjunctiva.

A 37-year-old man with a recurrent papillomatous lesion of the upper eyelid and four separate bulbar conjunctival ulcers was found to have North American blastomycosis. This represents the first reported case with conjunctival lesions that were not simply contiguous with eyelid involvement. This case underscores the importance of considering blastomycosis in the differential diagnosis of granulomatous conjunctivitis and when examining a lesion of the eyelid resembling a squamous cell carcinoma or atypical papilloma.     

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.     

Increased abdominal pain during final examinations

Anecdotes and animal experiments alike suggest that physiological and psychological stress can profoundly alter gastrointestinal function. However, few studies have examined, in humans, real-world stress to see if free-living persons exhibit gut alterations similar to those produced in the laboratory. To investigate this possibility, we studied 16 medical and premedical students during final written examinations. As compared to a control day, the examination created a classic stress response: elevated serum cortisol (16±1 to 21±3 µg/dl;P<0.05), ACTH (31±1 to 33±1 pg/ml;P<0.05), heart rate (72±3 to 79±3 beats/min;P<0.05), arterial blood pressure (systolic pressure 106±2 to 120±2 torr;P<0.05; diastolic pressure 72±2 to 77±1 torr;P<0.05), and subjective anxiety (raw score 28±2 to 47±3;P<0.0001). In contrast, subjects displayed identical orocecal liquid transit time (of 0.36 g/kg lactulose in a 240-ml, 250-kcal liquid meal) under control (103±8 min) and examination conditions (106±8 min;P=NS). Mean subjective reports of gas, diarrhea, and borborygmi were unchanged on the day of the experiment, although the examination did increase reported abdominal pain (from 0.5±0.4 to 2.1±0.5 on a 0–5 analog scale;P<0.05). We conclude that examination stress in humans can increase gastrointestinal symptoms without altering orocecal transit.     

You can't ask if you don't know what to ask: a survey of the information needs and resources of hospital outpatients.

OBJECTIVES: to test public demand for health and sickness information and identify sources of information used by the public. METHODS: using a questionnaire as the basis of a highly structured interview, 274 outpatients or their caregivers from nine clinics in Wellington Hospital, attending for the second or subsequent time, were asked whether they felt they knew enough about their illness and treatment, and where they had obtained their information. RESULTS: almost half expressed a wish for more illness information and two-fifths wanted to know more about their treatment. Respondents were significantly more satisfied with treatment than illness information. Outpatient comments further indicated dissatisfaction with information. Sixteen sources of information were each used by four or more people, almost 20% of the sample using more than six sources. Health professionals, the hospital doctor in particular, were the most important source of information; informal personal contacts were also widely used. CONCLUSIONS: the results highlight the difficulties of communication between health professionals and clients. The possibility of cooperation between health and information professionals in providing patients with more information is raised.