Alzheimer's disease and genetic testing.
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Aged↗
Biomedical subjects
A Lennox
Publications and source records attributed to A Lennox.
Workshop report: genetic testing programs for familial Alzheimer's disease.
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Aged↗
Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: II. Further cytogenetic analysis of the marker and characterization of the high-level repeat sequences using fluorescence in situ hybridization.
We have further characterized an unusual 22p+ marker chromosome with a double nucleolus organizer region (dNOR) previously identified in a family with late-onset dementia of the Alzheimer type. G-banding and morphology of the marker's q arm were typically normal. However, the p+ arm had a terminal cytological satellite and a GT-positive region at the midpoint. Standard C-banding documented 2 C-positive regions: one was associated with the primary centromere; the other, which was at the midpoint of the p arm, was not associated with a constriction. With replication-banding, there was a darkly staining region in the middle of the p+ arm that resembled the pericentromeric region of a chromosome 21 or 22. Fluorescence in situ hybridization with pXlr 101, a probe recognizing the full repeating unit of rDNA, indicated that the marker had an unusually larger rDNA region; with pU 1.2, a probe recognizing the human rDNA promoter, the signal was a doublet. The marker had 2 signals with a beta-satellite probe, and a second signal in addition to that present at the primary centromere under low stringency with alpha-satellite probes and a classic satellite probe. Immunostaining of chromosome spreads after R-banding and ultraviolet (UV) denaturation showed that the major portion of the marker's p arm was highly methylated.
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Monozygotic twins concordant for late-onset probable Alzheimer disease with suspected Alzheimer disease in four sibs.
Probable Alzheimer disease (AD) is described in 79-year-old male twins with monozygosity confirmed by DNA examination. The first twin to be affected began to show signs of intellectual deterioration at age 70. In the other, onset was at age 72. Four of their living sibs (current age range = 75-92) are also suspected to have AD. The possible roles of genetic and environmental factors in the development of AD in this sibship are discussed.
Aged↗
Normal tissue reactions and complications following high-energy neutron beam therapy: I. Crude response rates.
The incidence of significant complications (fibrosis, ulceration, necrosis of bone or soft tissue or serious functional impairment) was determined in relation to neutron dosage and follow-up time for 5 anatomical sites totalling 617 patients who had survived 2 or more years following treatment. The regions studied were head and neck (268 patients), thorax (lung and esophagus, 76 patients), upper abdomen (132 patients), pelvis (prostate and bladder, 114 patients) and extremities (27 patients). Neutron doses ranged from 16 to 28 Gy. All patients were followed until death or up to 10 years after treatment. A total of 109 complications were observed yielding a crude complication rate of 18% for the whole series. Observed complication rates were 7% in the 16-20 Gy dose range, 19% between 20 and 24 Gy, and 33% in patients receiving more than 24 Gy. Probit analysis of the data indicated a median effective dose (50% complications) of 29 (+/- 0.5) Gy with an estimated standard deviation of 8 Gy. A reasonable estimate of "tolerance" may then be taken as 29 - 8 = 21 Gy. Comparing the 5 anatomical sites revealed no significant differences in estimated tolerance doses. With the available data, no effect of field-size or target volume could be demonstrated. The incidence of complications apparently increases with time in long-term survivors. Although the overall incidence is only 18%, actuarial analysis of the data suggests that the complication rate might have exceeded 50% if all treated patients had survived 10 years. It is concluded that, with the exception of the nervous system and possibly other viscera, a neutron dose of 20 Gy (in 12 fractions over 4 weeks) represents a practical tolerance limit for all sites.
Abdomen↗
Failure of accelerated neutron therapy to control high grade astrocytomas.
Sixty-two patients with high grade malignant astrocytoma were treated with fast neutrons using three different treatment schemes to evaluate the effect of shortening the overall time. Dose and fraction number were kept constant. The total dose was 16-18 neutron Gy delivered in six fractions, weekly for 6 weeks, twice a week over 3-4 weeks, or three times a week over 2 weeks. There were no obvious differences in survival times among the three groups. We conclude that accelerated neutron therapy does not improve survival of patients with grade 3 and 4 astrocytoma.
Adult↗
Re-irradiation of locally recurrent tumors with fast neutrons.
Forty-six patients with locally recurrent disease were re-irradiated with fast neutrons at Fermilab. All had received prior radical radiation therapy either with or without surgery. Six were palliative. Forty patients treated with curative intent were analyzed for local response, survival, and complications. The overall response rate was 78% (31/40); 50% (20/40) had a complete local response. Ten of 16 patients (63%) with non-epidermoid carcinomas in the head and neck regions had complete response, whereas only nine of twenty patients (45%) with epidermoid carcinomas were complete responders. In a subset of 12 patients with salivary gland type tumors, 10 had a complete response (83%). Two of these 10 patients are alive beyond 5 years. Observed median survival for the forty patients was 9.3 months, and for complete responders 14.4 months. Observed median survival for partial responders was only 7.5 months. Four of six patients treated for palliation had significant subjective improvement. Significant morbidity, Grade III or greater (EORTC/RTOG scale), was seen in only 10 patients (25%), and this was found to depend directly on the total dose delivered. We conclude that neutron beam therapy can be used as a therapeutic modality for patients with recurrent tumors with an acceptable degree of morbidity.
Adenocarcinoma↗
An update on malignant salivary gland tumors treated with neutrons at Fermilab.
One hundred and thirteen cases of recurrent and/or unresectable malignant salivary gland tumors, treated with fast neutron therapy at Fermilab between September 1976 and December 1984, are analyzed for local control, sites of failure, and treatment-related morbidity. Sixty-three patients had major and 55 had minor salivary gland tumors. Local control was achieved in 67% of patients with major and 58% of patients with minor salivary gland tumors. In the subgroup of patients with oropharyngeal and oral cavity lesions, 19/24 (80%) had local control. However, only four of 15 patients with maxillary antrum tumors had successful control of their disease. Seventy-four percent of patients with lesions measuring 5 cm or less and 30% of patients with larger lesions had their local disease controlled. Histology did not influence the local control rate. Both observed and adjusted median survival for patients with major salivary gland tumors was 36 months. Disease-free survival was 31 months. Observed and adjusted median survivals for patients with minor salivary gland tumors are 48 and 57 months respectively. Twenty of 86 patients (23%) had major morbidity; this was directly related to the total dose delivered. In the dose range 20-24 Gy the complication rate was 16%. Most of these complications were successfully managed with minimal functional disability. We have concluded that fast neutron irradiation is an appropriate treatment for malignant salivary gland tumors.
Adult↗
Metabolism of some industrial uranium tetrafluorides after deposition in the rat lung.
UNLABELLED: Two commercially produced natural uranium tetrafluorides were administered to rats either by inhalation or direct injection into the lungs. THE RESULTS: show that, for both materials uranium is cleared rapidly from the lungs, much of it to the blood, show that the distribution of uranium amongst body tissues, and the fraction of the systemic content excreted in urine, is similar to that obtained after the administration of U(VI) bicarbonate, show that the transportability of uranium is much greater than in previously reported studies with other preparations of uranium tetrafluoride, suggest that lung radioactivity counting measurements would be of limited value for interpreting human exposures, indicate that for setting exposure limits these tetrafluorides should be considered moderately transportable compounds (ICRP inhalation class W).
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