Effect of maternal age on autosomal trisomies

The effect of maternal age on the genesis of trisomy was studied by comparing data from 362 trisomic and 790 chromosomally normal spontaneous abortions. As a group the trisomies were associated with a substantial increase in maternal age but there were considerable differences in the magnitude of the effect for different trisomies. The effect of increasing maternal age was most pronounced for trisomies involving the small chromosomes, both acrocentric and non-acrocentric. However, trisomy 16 was conspicuously different from trisomies for all the other small chromosomes, both in the reduced importance of increased maternal age and in the high frequency with which it occurred. The effect of increasing maternal age on trisomies for chromosomes in groups A, B and C was less clear than that for the small chromosomes. However, the evidence suggested that trisomy for these chromosomes was associated with a moderate increase in maternal age.
It was suggested that the maternal age-dependent trisomies might result from precocious disjunction of the bivalents and random segregation of the resulting univalents, a process which would affect chromosomes with the fewest number of chiasmata and which might be more prevalent in oocytes of older women. It was further suggested that true non-disjunction, that is, the failure of bivalents to separate at anaphase, might also result in the production of trisomies. This process might be independent of, or only slightly influenced by, increasing maternal age but be affected by the presence of large blocks of heterochromatin.     

Glucagon releasing activity of a cyclic peptide related to somatostatin

A possible benefit of creating smaller and more rigid active analogs of somatostatin is the discovery of compounds which selectively inhibit the secretion of insulin, glucagon or growth hormone. A series of cyclic tetrapeptide analogs related to somatostatin was synthesized, and one member of this series was found to cause an unexpected stimulation of glucagon secretion while having little if any effect on either insulin or growth hormone secretion. A sustained increase in plasma glucose levels was also observed. Two possible modes of action are proposed.     

Clinical Features of Multiple Glomus Tumors

BACKGROUND While glomus tumors are usually solitary, multiple glomus tumors do occur. The purpose of this study was to review the clinical characteristics and outcomes in a series of patients with multiple glomus tumors presenting to our institution.
METHODS A retrospective review of patients with multiple glomus tumors seen at our institution over the past 25 years was performed.
RESULTS Twenty-two patients with multiple glomus tumors were identified. Initial diagnosis was blue rubber nevus syndrome and hemangioma in 10 and 7 patients, respectively. The mean duration from onset of symptoms until correct diagnosis was 14.6 years. Involvement of an extremity was noted in 90.9% of the patients. An autosomal dominant pattern of inheritance was noted in 13 of 22 patients. The classic triad of symptoms in solitary glomus tumors—pain, pinpoint tenderness, and cold hypersensitivity—was noted in only 1 of the 22 patients; pain and pinpoint tenderness were simultaneously identified in 14 patients, 8 with visible lesions but no symptoms. Symptoms were relieved by surgical excision in most patients.
CONCLUSION Patients with multiple glomus tumors are frequently misdiagnosed. Proper recognition and diagnosis would lead to improved management.     

The Implantable Neurocybernetic Prosthesis System

The neurocybernetic prosthesis system (NCP) is an implantable, multiprogrammable pulse generator that delivers constant current electrical signals to the vagus nerve for the purpose of reducing the frequency and severity of epileptic seizures. The signals are delivered on a predetermined schedule, or may be initiated by the patient with an external magnet. The device is implanted in a subcutaneous pocket in the chest just below the clavicle, similar to pacemaker placement. The stimulation signal is transmitted from the prosthesis to the vagus nerve through a lead connected to an electrode which is a multi-turn silicone helix, with a platinum band on the inner turn of one helix. The prosthesis can be programmed with any IBM- compatible personal computer using NCP software and a programming wand.     

Paclitaxel activity for the treatment of non-Hodgkin's lymphoma: final report of a phase II trial

In order to determine the activity of paclitaxel in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial in which eligible patients received paclitaxel 200 mg/m² intravenously over 3 h. Treatment was repeated every 3 weeks. Patients achieving complete or partial responses after two courses of paclitaxel continued to receive therapy for a maximum of eight courses, otherwise they were removed from the study. Of 96 evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had relapsed lymphoma. The median number of prior treatment regimens was two (range one to 10 regimens). 45 patients had low-grade, 44 had intermediate-grade, and seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14 partial remissions) for an overall response rate of 25% (95% CI 17–35%). Patients with relapsed lymphoma had a higher response rate than those with primary refractory disease (19/51=37% v 5/45 =11%; P  < 0.01), and patients with relapsed intermediate-grade lymphoma had a higher response than those with relapsed low-grade lymphoma (9/18=50% v 10/31 = 32%; P  = 0.22). The treatment was very well tolerated with the most common side-effects being alopecia (100%), peripheral neuropathy (35% of ≥ grade II), and arthralgia/myalgia (25% of ≥ grade II). After the first course of paclitaxel, grade III/IV thrombocytopenia and neutropenia were observed in 21% and 23% of the patients respectively. 23 episodes of neutropenic fever developed after 250 courses of paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule, is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity of paclitaxel combination programmes are currently under investigation.     

A 90-Day Inhalation Toxicity Study of Raw Shale Oil in Fischer 344 Rats

A 90-Day Inhalation Toxicity Study of Raw Shale Oil in Fischer344 Rats. GORDON T., STROTHER, D. E., CRAMER, D. V., AND GOODE,J. W. (1987). Fundam. Appl. Pharmacol. 9, 287–296. Thepotential health effects of a raw shale oil were evaluated ina 90-day inhalation study in Fischer 344 rats. Groups of 15male and 15 female rats were exposed 6 hr/day, 5 days/week for13 weeks to aerosol concentrations of 0, 56, 120, or 492 mg/m³.In the high-dose group, 10 males and 7 females died prior tothe termination of the study, most within the first 5 weeksof the experiment. A dose-dependent suppression in weight gainwas seen in all of the shale oil-exposed groups. The failureto gain weight was associated with a variety of clinicopathologicabnormalities, including a dose-related decrease in red andwhite blood cells, with lowered plasma protein levels and increasedserum alkaline phosphatase, and with total bilirubin levelsin males. The exposure of the test animals to aerosolized rawshale oil was also associated with inflammatory and hyperplasticlesions in the lungs and upper respiratory tract, atrophy ofthe thyrnus and thymic-dependent portions of the peripherallymphoid system, and bone marrow. These changes demonstratethat inhalation of raw shale oil aerosol can produce major organtoxicity similar to that found after exposure to other unrefinedoil products.     

Disposition of the Aromatase Inhibitor LY56110 and Associated Induction and Inhibition Studies in Rats, Dogs, and Monkeys

Disposition of the Aromatase Inhibitor LY56110 and AssociatedInduction and Inhibition Studies in Rats, Dogs, and Monkeys.LINDSTROM, T. D., AND WHITAKER, G. W. (1987). Fundam. Appl.Toxicol. 8, 595–604. Compound LY56110 was well absorbedbut slowly excreted in the rat, dog, and monkey. Oral administrationof 5 mg/kg of [¹⁴C]LY56110 (5-bis(4-chlorophe-nyl)methylpyrimidine)to the rat, monkey, and dog resulted in a total excretion of68, 65, and 30% of the radioactivity within 5 days, respectively.Very low urinary excretion was observed in the rat and dog (2%),with fecal excretion being the predominant mode of eliminationin all three species. The plasma radioactivity half-life was49, 41, and greater than 100 hr in the rat, monkey, and dog,respectively. The plasma half-life of parent compound was 18hr in the rat and 10 hr in the dog. LY56110 accounted for only25, 12, and 1% of the plasma radioactivity area under the curvein the rat, dog, and monkey, respectively. High levels of radioactivitywere observed in the target tissues of fat, adrenals, and ovariesof rats. LY56110 induced hepatic cytochromes b₅ and P-450 andcytochrome c reductase in rats after 14 days of oral dosingat 10 mg/kg but not in monkeys after 10 days of oral dosingat 10 mg/kg. The compound was more potent than aminoglutethimideor cimetidine in inhibiting hepatic ethylmorphine and p-nitro-anisoledemethylase activity in vitro. LY56110 also inhibited ethinamate-inducedsleeping time in rats in vivo. The compound induced a reversetype I binding spectrum with rat ovarian microsomes.