I claim:
1. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base, the sample mount further comprising:
a first clamp member;
a second opposing clamp member, the clamp members being capable of securing a sample therebetween; and
a lead screw operatively connected to both clamp members, whereby rotation of the lead screw varies the distance between the clamp members.
2. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber wherein the base has a central opening; and
a sample mount removably connected to the base, the sample mount comprising:
a first clamp member;
a second opposing clamp member, the clamp members being capable of securing a sample therebetween; and
a lead screw operatively connected to the first and second clamp members, whereby rotation of the lead screw varies the distance between the clamp members.
3. The electron microscope of claim 2 further comprising a rail, the base being adjustably positionable relative to the rail.
4. The electron microscope of claim 2 further comprising means to retain the sample mount within the base.
5. The electron microscope of claim 4 wherein the retaining means comprises a pin disposed on the sample mount wherein the central opening on the base receives the pin when the sample mount is connected to the base.
6. The electron microscope of claim 2 wherein the lead screw additionally comprises means to assist in turning the lead screw.
7. The electron microscope of claim 2 wherein both clamp members are movable relative to the base.
8. The electron microscope of claim 2 wherein one clamp member is fixed relative to the base.
9. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base,
the sample mount for retaining a sample for viewing with the electron microscope further comprising:
a retaining assembly comprising:
a plate having a first side and a second side; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate;
a first clamp member operatively connected to the retaining assembly;
a second opposing clamp member operatively connected to the retaining assembly, the clamp members being capable of securing the sample therebetween; and
a lead screw secured to the retaining assembly and operatively connected to the first and second clamp members.
10. A sample mount for retaining a sample for viewing with an electron microscope further comprising:
a retaining assembly comprising:
a plate having a first side and a second side; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate;
a first clamp member operatively connected to the retaining assembly;
a second opposing clamp member operatively connected to the retaining assembly, the clamp members being capable of securing the sample therebetween; and
a lead screw secured to the retaining assembly and operatively connected to the first and second clamp members, wherein the plate further comprises a pair of opposing tabs extending away from the first side of the plate, the tabs being spaced apart by a tab separation.
11. The sample mount of claim 10 wherein each tab of the lead screw has a centrally located first convex radius.
12. The sample mount of claim 11 wherein the first side of the clamp body defines a pair of opposing recesses for receiving the tabs, each recess having a second centrally located convex radius substantially equal in size to the first convex radius such that when the plate is attached to the clamp body, the interrelation of the first and second convex radii define a pair of opposing cylindrical openings, the openings having a retaining diameter.
13. The sample mount of claim 12 wherein the clamp body has a centrally located slot therein extending generally between the opposing recesses, the slot having a slot width.
14. The sample mount of claim 13 wherein the clamp body is separable into a first half and a second half.
15. The sample mount of claim 14 wherein the first half of the clamp body is separable from the second half of the clamp body along a line generally perpendicular to the slot.
16. The sample mount of claim 14 wherein the clamp members have a first portion and a second portion, the second portion having a width slightly less than the slot width such that the second portion of each clamp member nests within the slot of the clamp body.
17. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base,
the sample mount for retaining a sample for viewing with an electron microscope further comprising:
a retaining assembly comprising:
a plate having a first side and a second side wherein the first side comprises a pair of opposing tabs extending away from the first side and each tab has a centrally located first convex radius, the tabs being spaced apart by a tab separation; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate, wherein the first side of the clamp body defines a pair of opposing recesses for receiving the tabs, each recess having a second centrally located convex radius substantially equal in size to the first convex radius such that when the plate is attached to the clamp body, the interrelation of the first and second convex radii define a pair of opposing cylindrical openings, the openings having a retaining diameter, and wherein the clamp body has a centrally located slot therein extending generally between the opposing recesses, the slot having a slot width;
a first clamp member operatively connected to the retaining assembly;
a second opposing clamp member operatively connected to the retaining assembly, the clamp members being capable of securing the sample therebetween, wherein the clamp members have a first portion and a second portion, the second portion having a width slightly less than the slot width such that the second portion of each clamp member nests within the slot of the clamp body, wherein the second portion of the first clamp member has a first threaded opening therein, said first threaded opening having a right-handed thread, and the second portion of the second clamp member has a second threaded opening therein, said second threaded opening having a left-handed thread; and
a lead screw secured to the retaining assembly and threadably coupled to the first and second threaded openings.
18. The electron microscope of claim 17 wherein the clamp body is separable into a first half and a second half.
19. The electron microscope of claim 17 wherein the lead screw comprises:
a central threaded portion having a minor diameter;
a first end portion located at each end immediately adjacent to the central threaded portion wherein the first end portion and the central threaded portion together define a screw length which is slightly less than the tab separation; and
a second non-threaded portion located immediately outboard of each first end portion, the second non-threaded portion having a second diameter.
20. The electron microscope of claim 19 wherein the first end portion defines a first non-threaded portion having a first diameter.
21. The electron microscope of claim 20 wherein the first diameter is less than the minor diameter, and the second diameter is less than the first diameter and is also less than the retaining diameter such that, when installed in the retaining assembly, the second non-threaded portion is retained within the opposed cylindrical openings, permitting rotation of the lead screw but restraining it from longitudinal motion.
22. The electron microscope of claim 21 wherein the central threaded portion of the lead screw further comprises a first threaded portion having a right-handed thread threadably engaged with a first threaded opening of the first clamp member and a second threaded portion having a left-handed thread threadably engaged with a second threaded opening of the second clamp member, whereby rotation of the lead screw in a first direction results in relative closure of the clamp members and rotation of the lead screw in a second direction results in relative separation of the clamp members.
23. The electron microscope of claim 17 wherein the clamp members move toward and away from a common origin.
24. The electron microscope of claim 17 wherein a thumb-wheel is secured to at least one end of the lead screw.
25. The electron microscope of claim 17 wherein the retaining assembly, first and second clamp members, and the lead screw are removably secured to a base.
26. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base,
the sample mount for use with an electron microscope further comprising:
a retaining assembly comprising:
a plate having a first side and a second side; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate and the second side of the clamp body defining a fixed clamp face;
a clamp member operatively connected to the retaining assembly; and
a lead screw secured to the retaining assembly and operatively connected to the clamp member.
27. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base,
the sample mount for use with an electron microscope further comprising:
a retaining assembly comprising:
a plate having a first side and a second side; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate and the second side of the clamp body defining a fixed clamp face;
a clamp member operatively connected to the retaining assembly; and
a lead screw secured to the retaining assembly and operatively connected to the clamp member, wherein the plate further comprises a pair of opposing tabs extending away from the first side of the plate, the tabs being spaced apart by a tab separation.
28. The electron microscope of claim 27 wherein each tab has a centrally located first convex radius.
29. The electron microscope of claim 28 wherein the first side of the clamp body defines a pair of opposing recesses for receiving the tabs, each recess having a second centrally located convex radius substantially equal to the first convex radius such that when the plate is connected to the clamp body, the interrelation of the first and second convex radii define a pair of opposing cylindrical openings, the openings having a retaining diameter.
30. The electron microscope of claim 29 wherein the clamp body has a centrally located slot therein extending generally between the opposing recesses, the slot having a slot width.
31. The electron microscope of claim 30 wherein the clamp member has a first portion substantially identical in size and in opposing relation to the clamp face, and a second portion, the second portion having a width slightly less than the slot width such that the second portion of the clamp member nests within the slot of the clamp body.
32. The electron microscope of claim 31 wherein the second portion of the clamp member has a threaded opening therein.
33. An electron microscope comprising:
an electron beam source;
a vacuum chamber coupled to the electron beam source;
a base within the vacuum chamber; and
a sample mount removably coupled to the base,
the sample mount for use with an electron microscope comprising:
a retaining assembly comprising:
a plate having a first side and a second side wherein the first side comprises a pair of opposing tabs extending away from the first side and each tab has a centrally located first convex radius, the tabs being spaced apart by a tab separation; and
a clamp body having a first side and a second side, the first side of the clamp body being removably attached to the first side of the plate and the second side of the clamp body defining a fixed clamp face, wherein the first side of the clamp body defines a pair of opposing recesses for receiving the tabs, each recess having a second centrally located convex radius substantially equal in size to the first convex radius such that when the plate is attached to the clamp body, the interrelation of the first and second convex radii define a pair of opposing cylindrical openings, the openings having a retaining diameter, and wherein the clamp body has a centrally located slot therein extending generally between the opposing recesses, the slot having a slot width;
a clamp member operatively connected to the retaining assembly wherein the clamp member has a first portion substantially identical in size and in opposing relation to the clamp face, and a second portion, the second portion having a width slightly less than the slot width such that the second portion of the clamp member nests within the slot of the clamp body and wherein the second portion of the clamp member has a threaded opening therein; and
a lead screw secured to the retaining assembly and operatively connected to the clamp member.
34. The electron microscope of claim 33 wherein the lead screw comprises:
a central threaded portion having a minor diameter;
a first end portion located at each end immediately adjacent to the central threaded portion wherein the first end portion and the central threaded portion together define a screw length which is slightly less than the tab separation; and
a second non-threaded portion located immediately outboard of each first end portion, the second non-threaded portion having a second diameter.
35. The electron microscope of claim 34 wherein the first end portion defines a first non-threaded portion having a first diameter.
36. The electron microscope of claim 35 wherein the first diameter is less than the minor diameter and the second diameter is less than the first diameter and is also less than the retaining diameter such that, when installed in the retaining assembly, the second non-threaded portion is retained within the opposed cylindrical openings, permitting rotation of the lead screw but restraining it from longitudinal motion.
37. The electron microscope of claim 36 wherein the central threaded portion is threadably engaged with the threaded opening of the second portion of the clamp member, whereby rotation of the lead screw in a first direction results in movement of the clamp member towards the clamp face and rotation of the lead screw in a second direction results in movement of the clamp member away from the clamp face.
38. The electron microscope of claim 33 wherein a thumb-wheel is secured to at least one end of the lead screw.
39. A method of examining a sample in an electron microscope comprising:
retaining the sample further comprising:
securing a sample mount to a base;
inserting a sample into the sample mount; and
turning a lead screw of the sample mount in a first direction to move a first clamp member toward a second clamp member thereby securing the sample therebetween;
pumping down a chamber to form a vacuum chamber; and
coupling an electron beam source to the chamber.
40. The method of claim 39 further comprising securing a plurality of silicon wafers between the clamp members to form the sample.
41. The method of claim 39 further comprising turning the lead screw in a second direction to move the first clamp member away from the second clamp member thereby releasing the sample.
42. The method of claim 39 further comprising providing a thumb-wheel to assist in turning the lead screw.
43. A method of examining a sample in an electron microscope comprising:
retaining the sample which further comprises:
securing a sample mount to a base;
inserting a sample into the sample mount;
turning a lead screw in a first direction to move both a first clamp member and a second clamp member toward the sample thereby securing the sample therebetween; and
turning the lead screw in a second direction to move both the first clamp member and the second clamp member away from the sample thereby releasing the sample;
pumping down a chamber to form a vacuum chamber; and
coupling an electron beam source to the chamber.
44. The method of claim 43 further comprising securing a plurality of silicon wafers between the clamp members to form the sample.
45. The method of claim 43 further comprising providing a thumb-wheel to assist in turning the lead screw.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for increasing the therapeutic effect of an acetylcholinesterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia, which comprises administering to said patient said AChEI at a dose level which is higher than the recommended maximal dose level, in combination with a compound that reduces, including to the extent of eliminating, dose-limiting side effects of said AChEI dose level, said compound being a non-anticholinergic antiemetic agent.
2. The method of claim 1, wherein said dose level is increased up to a factor of 4.
3. The method of claim 1, wherein said AChEI is administered to said patient concurrently or sequentially with said non-anticholinergic antiemetic agent, whereby an enhanced acetylcholinesterase inhibition in the CNS of said patient is achieved and the symptoms of an Alzheimer type dementia in said patient are improved.
4. The method of claim 1, wherein said AChEI is administered to said patient at a dose level which is from 1.5 to 3 times higher than the recommended dose in the treatment of Alzheimer type dementia.
5. The method of claim 1, wherein the non-anticholinergic antiemetic agent is formulated in a pharmaceutical composition, in admixture with a pharmaceutical carrier, in an amount of from 50% to 300% of the dosage used for preventing vomiting.
6. The method of claim 1, wherein said non-anticholinergic antiemetic agent is selected from the group consisting of 5-HT3 receptor antagonists, dopamine antagonists, H1 histamine receptor antagonists, NK1 receptor antagonists and cannabinoid agonists.
7. The method of claim 6, wherein said non-anticholinergic antiemetic agent is a 5HT3-antagonist selected from the group consisting of ondansetron, the pharmaceutically acceptable salts and solvates of ondansetron, granisetron, the pharmaceutically acceptable salts and solvates of granisetron, tropisetron, the pharmaceutically acceptable salts and solvates of tropisetron, lerisetron, the pharmaceutically acceptable salts and solvates of lerisetron, ramosetron and the pharmaceutically acceptable salts and solvates of ramosetron.
8. The method of claim 6, wherein said dopamine antagonist is selected from the group consisting of domperidone, the pharmaceutically acceptable salts of domperidone, metoclopramide, the pharmaceutically acceptable salts and solvates of metoclopramide, bromopride, the pharmaceutically acceptable salts of bromopride, clebopride, the pharmaceutically acceptable salts of clebopride, alizapride and the pharmaceutically acceptable salts of alizapride.
9. The method of claim 6, wherein said H1 histamine receptor antagonist is meclizine or a pharmaceutically acceptable salt or solvate thereof.
10. The method of claim 6, wherein said cannabinoid agonist is dronabinol or nabilone.
11. The method of claim 6, wherein said NK1 receptor antagonist is aprepitant or casopitant.
12. The method of claim 6, wherein said AChEI is selected from the group consisting of 1,2,3,4-tetrahydro-9-acridinamine (tacrine); (1R,9S,13 E)-1-amino-13-ethylidene-11-methyl-6-azatricyclo7.3.1.02,7trideca-2 (7),3,10-trien-5-one (huperzine A); (\xb1)-2,3-dihydro-5,6-dimethoxy-2-1-(phenylmethyl)-4-piperidinylmethyl-1H-inden-1-one (donepezil) and pharmaceutically acceptable salts thereof; (S)\u2014N-Ethyl-N-methyl-3-1-(dimethylamino)ethyl-phenyl carbamate (rivastigmine) and pharmaceutically acceptable salts thereof; and 4aS,6R,8aS-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydroxy-6H-benzofuro3a,3,2-e,fbenzazepin-6-ol (galantamine) and its pharmaceutically acceptable salts thereof.
13. The method of claim 5, wherein said pharmaceutical composition containing the non-anticholinergic antiemetic agent is in a unit form also containing an AChEI.
14. A pharmaceutical unit form which comprises
(a) a non-anticholinergic antiemetic agent selected from the group consisting of 5-HT3 receptor antagonists, dopamine antagonists, H1 histamine receptor antagonists, cannabinoid agonists, aprepitant and casopitant; and
(b) an AChEI;
in admixture with a pharmaceutical carrier.
15. The unit form of claim 14 wherein said non-anticholinergic antiemetic agent is selected from the group consisting of ondansetron and pharmaceutically acceptable salt thereof, in an amount (in ondansetron) of from 2 mg to 24 mg; granisetron and pharmaceutically acceptable salt thereof, in an amount (in granisetron) of from 0.5 mg to 3 mg; domperidone and pharmaceutically acceptable salts thereof, in an amount (in domperidone) of from 5 mg to 30 mg; metoclopramide and pharmaceutically acceptable salts and solvates thereof, in an amount (in metoclopramide) of from 5 mg to 30 mg; dronabinol, in an amount of from 1.25 mg to 30 mg; nabilone, in an amount of from 0.25 mg to 3 mg; aprepitant, in an amount of from 20 mg to 375 mg; and casopitant, in an amount of from 25 mg to 150 mg.
16. The unit form of claim 14, wherein said AChEI is selected from the group consisting of phenserine and pharmaceutically acceptable salts thereof, in an amount (in phenserine) of from 15 to 45 mg; tacrine, in an amount of from 10 mg to 120 mg; huperzine A, in an amount of from 50 \u03bcg to 400 \u03bcg; donepezil and pharmaceutically acceptable salts thereof, in an amount (in donepezil) of from 5 mg to 30 mg; rivastigmine and pharmaceutically acceptable salts thereof, in an amount (in rivastigmine) of from 1.5 mg to 18 mg; galantamine and pharmaceutically acceptable salts thereof, in an amount (in galantamine) of from 4 mg to 36 mg.
17. The unit form of claim 14, wherein said AChEI is selected from the group consisting of donepezil and pharmaceutically acceptable salts thereof, in an amount (in donepezil) of from 15 mg to 30 mg; rivastigmine and pharmaceutically acceptable salts thereof, in an amount (in rivastigmine) of from 9 mg to 18 mg; and galantamine and pharmaceutically acceptable salts thereof, in an amount (in galantamine) of from 16 mg to 36 mg.
18. The unit form of claim 14, wherein said AChEI is selected from the group consisting of rivastigmine and pharmaceutically acceptable salts thereof, in an amount (in rivastigmine) of from 10 mg to 24 mg; and galantamine and pharmaceutically acceptable salts thereof, in an amount (in galantamine), of from 24 mg to 72 mg; said unit form being formulated for ER administration.
19. The unit form of claim 14, wherein
(a) the non-anticholinergic antiemetic agent is selected form the group consisting of ondansetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in ondansetron) of from 2 mg to 16 mg; granisetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in granisetron) of from 0.5 mg to 2 mg; domperidone and pharmaceutically acceptable salts and solvates thereof, in an amount (in domperidone) of from 5 mg to 20 mg; metoclopramide and pharmaceutically acceptable salts and solvates thereof, in an amount (in metoclopramide) of from 5 mg to 20 mg; dronabinol, in an amount of from 1.25 mg to 20 mg; nabilone, in an amount of from 0.25 mg to 2 mg; aprepitant, in an amount of from 20 mg to 250 mg; and casopitant, in an amount of from 25 mg to 100 mg; and
(b) the AChEI is selected from the group consisting of donepezil and pharmaceutically acceptable salts thereof, in an amount (in donepezil) of from 15 mg to 30 mg; rivastigmine and pharmaceutically acceptable salts thereof, in an amount (in rivastigmine) of from 9 mg to 18 mg; and galantamine and pharmaceutically acceptable salts thereof, in an amount (in galantamine) of from 16 mg to 36 mg;
said unit form being formulated as IR oral composition.