All The Claims

1. A pharmaceutical composition comprising, as a first active ingredient, a vitamin D analogue capable of upregulating the expression of cytidine deaminase in tumour cells and, as a second active ingredient, a cytostatic pyrimidine nucleoside analogue together with a pharmaceutically acceptable excipient or vehicle.
2. A composition according to claim 1, wherein the pyrimidine nucleoside analogue is a fluoropyrimidine prodrug.
3. A composition according to claim 2, wherein the fluoropyrimidine prodrug is selected from the group consisting of capecitabine and galocitabine.
4. A composition according to any of claims 1-3, wherein the vitamin D analogue is one which exhibits an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase expression upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
5. A composition according to claim 2, wherein the vitamin D analogue is one which is capable of upregulating the expression of both cytidine deaminase and thymidine phosphorylase in tumour cells so as to effect increased levels of conversion of said fluoropyrimidine prodrug to 5-fluorouracil in tumour cells.
6. A composition according to any of claims 1-5, wherein the vitamin D analogue is a compound of formula I
3
wherein p1 n is 2 or 3, m is 0 or an integer from 1 to 4;
R1 and R2, which are the same or different, are independently hydrogen or C1-8 hydrocarbyl or, together with the carbon atom to which they are attached (marked with an asterisk in formula I), R1 and R2 form a saturated or unsaturated C3-8 carbocyclic ring,
R1 andor R2 andor one of the m carbon atoms (marked with o in formula I) being optionally substituted by one or more chloro or fluorine atoms or C1-2 alkyl; or derivatives of compounds of formula I in which one or more hydroxy groups are transformed into O-acyl or O-glycosyl or phosphate ester groups, such masked groups being hydrolysable in vivo.
7. A composition according to claim 6, wherein the compound of formula I is seocalcitol.
8. A pharmaceutical combination composition comprising, in separate containers and intended for simultaneous or sequential administration, a vitamin D analogue capable of upregulating the expression of cytidine deaminase in tumour cells as a first active ingredient together with a pharmaceutically acceptable excipient or vehicle and a cytostatic pyrimidine nucleoside analogue as a second active ingredient together with a pharmaceutically acceptable excipient or vehicle.
9. A composition according to claim 8, wherein the pyrimidine nucleoside analogue is a fluoropyrimidine prodrug.
10. A composition according to claim 9, wherein the fluoropyrimidine prodrug is selected from the group consisting of capecitabine and galocitabine.
11. A composition according to any of claims 8-10, wherein the vitamin D analogue is one which exhibits an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase expression upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
12. A composition according to claim 9, wherein the vitamin D analogue is one which is capable of upregulating the expression of both cytidine deaminase and thymidine phosphorylase in tumour cells so as to effect increased levels of conversion of said fluoropyrimidine prodrug to 5-fluorouracil in tumour cells.
13. A composition according to any of claims 8-12, wherein the vitamin D analogue is a compound of formula I
4
wherein
n is 2 or 3, m is 0 or an integer from 1 to 4;
R1 and R2, which are the same or different, are independently hydrogen or C1-8 hydrocarbyl or, together with the carbon atom to which they are attached (marked with an asterisk in formula I), R1 and R2 form a saturated or unsaturated C3-8 carbocyclic ring,
R1 andor R2 andor one of the m carbon atoms (marked with o in formula I) being optionally substituted by one or more chloro or fluorine atoms or C1-2 alkyl; or derivatives of compounds of formula I in which one or more hydroxy groups are transformed into O-acyl or O-glycosyl or phosphate ester groups, such masked groups being hydrolysable in vivo.
14. A composition according to claim 13, wherein the compound of formula I is seocalcitol.
15. Use of a vitamin D analogue capable of upregulating the expression of cytidine deaminase in tumour cells in combination with a cytostatic pyrimidine nucleoside analogue for the preparation of a medicament for the treatment or amelioration of neoplastic diseases or conditions.
16. The use of claim 15, wherein the pyrimidine nucleoside analogue is a fluoropyrimidine prodrug.
17. The use of claim 16, wherein the fluoropyrimidine prodrug is selected from the group consisting of capecitabine and galocitabine.
18. The use of any of claims 15-17, wherein the vitamin D analogue is one which exhibits an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase expression upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
19. The use of claim 16, wherein the vitamin D analogue is one which is capable of upregulating the expression of both cytidine deaminase and thymidine phosphorylase in tumour cells so as to effect increased levels of conversion of said fluoropyrimidine prodrug to 5-fluorouracil in tumour cells.
20. The use of any of claims 15-19, wherein the vitamin D analogue is a compound of formula I
5
wherein
n is 2 or 3, m is 0 or an integer from 1 to 4;
R1 and R2, which are the same or different, are independently hydrogen or C1-8 hydrocarbyl or, together with the carbon atom to which they are attached (marked with an asterisk in formula I), R1 and R2 form a saturated or unsaturated C3-8 carbocyclic ring,
R1 andor R2 andor one of the m carbon atoms (marked with o in formula I) being optionally substituted by one or more chloro or fluorine atoms or C1-2 alkyl; or derivatives of compounds of formula I in which one or more hydroxy groups are transformed into O-acyl or O-glycosyl or phosphate ester groups, such masked groups being hydrolysable in vivo.
21. The use of claim 20, wherein the compound of formula I is seocalcitol.
22. The use of claim 15, wherein the medicament comprises the vitamin D analogue and the pyrimidine nucleoside analogue in separate containers intended for simultaneous or sequential administration of the vitamin D analogue and the pyrimidine nucleoside analogue.
23. The use of claim 22, wherein the medicament comprises the vitamin D analogue and the pyrimidine nucleoside analogue in unit dosage form.
24. The use according to any of claims 15-23, wherein the neoplastic disease or condition is selected from the group consisting of gastrointestinal cancer, including colorectal cancer, liver cancer, breast cancer, pancreatic cancer, head and neck cancer, bladder cancer, ovarian cancer and endometrial cancer.
25. A method of treating or ameliorating neoplastic diseases or conditions, the method comprising administering, to a subject in need thereof, an effective amount of a vitamin D analogue capable of upregulating the expression of cytidine deaminase in tumour cells and, simultaneously or sequentially therewith, administering an effective amount of a pyrimidine nucleoside analogue.
26. The method of claim 25, wherein the pyrimidine nucleoside analogue is a fluoropyrimidine prodrug.
27. The method of claim 26, wherein the fluoropyrimidine prodrug is selected from the group consisting of capecitabine and galocitabine.
28. The method of any of claims 25-27, wherein the vitamin D analogue is one which exhibits an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase expression upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
29. The method of claim 26, wherein the vitamin D analogue is one which is capable of upregulating the expression of both cytidine deaminase and thymidine phosphorylase in tumour cells so as to effect increased levels of conversion of said fluoropyrimidine prodrug to 5-fluorouracil in tumour cells.
30. The method of any of claims 25-29, wherein the vitamin D analogue is a compound of formula I
6
wherein
n is 2 or 3, m is 0 or an integer from 1 to 4;
R1 and R2, which are the same or different, are independently hydrogen or C1-8 hydrocarbyl or, together with the carbon atom to which they are attached (marked with an asterisk in formula I), R1 and R2 form a saturated or unsaturated C3-8 carbocyclic ring,
R1 andor R2 andor one of the m carbon atoms (marked with o in formula I) being optionally substituted by one or more chloro or fluorine atoms or C1-2 alkyl; or derivatives of compounds of formula I in which one or more hydroxy groups are transformed into O-acyl or O-glycosyl or phosphate ester groups, such masked groups being hydrolysable in vivo.
31. The method of claim 30, wherein the compound of formula I is seocalcitol.
32. A method of providing increased conversion of a fluoropyrimidine prodrug to 5-fluorouracil in a tumour cell, the method comprising contacting a tumour cell with an effective amount of a fluoropyrimidine prodrug and, simultaneously or sequentially therewith, contacting said tumour cell with an effective amount of a vitamin D analogue capable of upregulating the expression of cytidine deaminase in said cell.
33. The method of claim 32, wherein the vitamin D analogue is one which exhibits an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase expression upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
34. The method of claim 32, wherein the vitamin D analogue is one which is capable of upregulating the expression of both cytidine deaminase and thymidine phosphorylase in tumour cells.
35. The method of any of claims 32-34, wherein the vitamin D analogue is a compound of formula I
7
wherein
n is 2 or 3, m is 0 or an integer from 1 to 4;
R1 and R2, which are the same or different, are independently hydrogen or C1-8 hydrocarbyl or, together with the carbon atom to which they are attached (marked with an steris in formula I), R1 and R2 form a saturated or unsaturated C3-8 carbocyclic ring,
R1 andor R2 andor one of the m carbon atoms (marked with o in formula I) being optionally substituted by one or more chloro or fluorine atoms or C1-2 alkyl; or derivatives of compounds of formula I in which one or more hydroxy groups are transformed into O-acyl or O-glycosyl or phosphate ester groups, such masked groups being hydrolysable in vivo.
36. The method of claim 35, wherein the compound of formula I is seocalcitol.
37. The method of any of claims 32-36, wherein the fluoropyrimidine prodrug is selected from the group consisting of capecitabine and galocitabine.
38. A method of screening for vitamin D analogues with an increased activity in upregulating the expression of cytidine deaminase in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3, the method comprising (a) contacting tumour cells expressing cytidine deaminase with one or more test vitamin D analogues for a period of time sufficient for said analogues to exert an effect on the expression of cytidine deaminase in said cells, (b) determining the level of cytidine deaminase expression in cells treated with said analogues compared to the level of cytidine deaminase expression in untreated control cells, and (c) selecting vitamin D analogue(s) which, when in contact with said cells, result in upregulation of cytidine deaminase expression.
39. The method of claim 38, wherein 1, 25-dihydroxyvitamin D3 is additionally used in step (b) as a positive control.
40. The method of claim 38 or 39, wherein, in step (c), vitamin D analogues are selected which exhibit an at least 50%, preferably at least 75%, e.g. at least 100%, higher cytidine deaminase upregulating activity in tumour cells compared to the activity of 1, 25-dihydroxyvitamin D3.
41. The method of claim 40, wherein the vitamin D analogue selected in step (c) is seocalcitol.
42. The method of any of claims 38-41 comprising the further step of selecting vitamin D analogue(s) which, when in contact with said cells, result in upregulation of both cytidine deaminase and thymidine phosphorylase expression.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

What is claimed is:

1. A catalyst for exhaust gas purification capable of purifying the hydrocarbons, nitrogen oxides and carbon monoxide present in the exhaust gas discharged from an internal combustion engine, which catalyst comprises a monolithic carrier and a catalyst layer containing Pd, Ba and a heat-resistant inorganic oxide, formed on the carrier, wherein the amount of Pd supported on monolithic carrier is 100-300 g per ft3 of monolithic carrier (3.53103 to 1.06102 g per cc of monolithic carrier), the amount of Ba supported on monolithic carrier is 0.010-0.060 g per cc of monolithic carrier in terms of BaO, and the weight ratio of Pd and Ba as expressed as BaO is 1:2 to 1:10.
2. A catalyst for exhaust gas purification according to claim 1, wherein the heat-resistant inorganic oxide is active alumina.
3. A catalyst for exhaust gas purification according to claim 1, wherein the Pd and Ba in the catalyst layer are supported on the heat-resistant inorganic oxide.
4. A catalyst for exhaust gas purification according to claim 3, wherein at least part of the Pd is supported on the heat-resistant inorganic oxide in direct contact therewith.
5. A catalyst for exhaust gas purification according to claim 4, wherein part of the Pd is supported on the heat-resistant inorganic oxide in direct contact therewith, the rest of the Pd is supported on the Ba supported on the heat-resistant inorganic oxide, and the amount of the Pd supported on the heat-resistant inorganic oxide in direct contact therewith is larger than the amount of the Pd supported on the Ba supported on the heat-resistant inorganic oxide.
6. A catalyst for exhaust gas purification according to claim 3, wherein the total amount of Pd is supported on the heat-resistant inorganic oxide in direct contact therewith.
7. A catalyst for exhaust gas purification according to claim 1, wherein the catalyst layer on the monolithic carrier is formed by coating, on the monolithic carrier, a slurry of pH 10 or more containing the components of the catalyst layer.
8. A catalyst for exhaust gas purification according to claim 1, wherein the catalyst layer further contains a noble metal other than Pd.
9. A catalyst for exhaust gas purification according to claim 8, wherein the noble metal other than Pd is Rh.
10. A catalyst for exhaust gas purification according to claim 8, wherein the catalyst layer is divided into a Pd- and Ba-containing layer and a layer containing a noble metal other than Pd (and containing no Ba) and the two layers are formed apart on one same monolithic carrier by coating.
11. A catalyst for exhaust gas purification according to claim 10, wherein the Pd- and Ba-containing layer and the layer containing a noble metal other than Pd (and containing no Ba) are formed in two laminated layers on one same monolithic carrier.
12. A catalyst for exhaust gas purification according to claim 11, wherein the layer containing a noble metal other than Pd (and containing no Ba) is laminated on the Pd- and Ba-containing layer.
13. A catalyst for exhaust gas purification according to claim 1, which is useful for purification of the harmful substances present in the exhaust gas discharged from an internal combustion engine during the cold start.
14. A catalyst for exhaust gas purification according to claim 1, wherein the catalyst layer further contains CeO2.
15. A catalyst for exhaust gas purification according to claim 1, wherein the catalyst layer is produced by supporting Pd on a heat-resistant inorganic oxide and then supporting Ba on the Pd-supported heat-resistant inorganic oxide.
16. A system for exhaust gas purification comprising:
a catalyst for exhaust gas purification comprising a monolithic carrier and a catalyst layer containing Pd, Ba and a heat-resistant inorganic oxide, formed on the carrier, wherein the amount of Pd supported on monolithic carrier is 100-300 g per ft3 of monolithic carrier (3.53103 to 1.06102 g per cc of monolithic carrier), the amount of Ba supported on monolithic carrier is 0.010-0.060 g per cc of monolithic carrier in terms of BaO, and the weight ratio of Pd and Ba as expressed as BaO is 1:2 to 1:10, provided in the exhaust pipe of internal combustion engine, and
an adsorbent having hydrocarbon adsorbability, also provided in the exhaust pipe.
17. A system for exhaust gas purification according to claim 16, further comprising a different catalyst provided in the exhaust pipe.
18. A system for exhaust gas purification according to claim 17, wherein the different catalyst contains Pd as a catalyst active component.

1. A pole base comprising:
a body having an upper portion; and
a pole attachment device disposed on the upper portion of the body, wherein the pole attachment device is a separate plate having a plurality of slots wherein:
the separate plate is configured to removeably receive and secure a plurality of fastener assemblies such that each of the plurality of fastener assemblies may be received in one of the plurality of slots in a plurality of locations along a length of each slot;
a lower portion of each fastener assembly abuts a bottom surface of the separate plate;
reinforcing steel is welded directly to the separate plate; and the separate plate comprises a center hole and each of the plurality of slots are radially oriented such that a head or a nut from each of the plurality of fastener assemblies may pass through the center hole and a shaft of each of the plurality of fastener assemblies may pass through the plurality of slots trapping either the head or the nut under the separate plate.
2. The pole base of claim 1, wherein the body comprises concrete and the reinforcing steel is contained within the body when the separate plate is disposed on the upper portion of the body.
3. The pole base of claim 1, wherein each of the plurality of slots extends through an entire thickness of the separate plate without reaching any outer periphery of the separate plate.
4. The pole base of claim 1, wherein the upper portion of the body comprises a recess configured such that the separate plate is generally flush with an upper surface of the upper portion of the body when the separate plate is received within the recess.
5. The pole base of claim 1, wherein:
the recess comprises: a recessed area configured to correspond to a shape of the separate plate; a central cavity configured to correspond to the center hole; and a plurality of recessed channels configured to correspond to the plurality of slots; and
the body comprises one or more internal conduits that extend from the central cavity to an exit at a side or a bottom of the body.
6. The pole base of claim 1, further comprising a lifting device configured to attach to the separate plate, the lifting device comprising (a) a single channel with two or more holes to receive fastener assemblies that attach to two of the plurality of slots of the separate plate and (b) a lifting lug attached to an upper surface of the single channel.
7. The pole base of claim 6, wherein the two or more holes are disposed such that the fastener assemblies are respectively received in an opposite pair of the plurality of slots and the fastener assemblies, when moving in the plurality of slots, remain in the plurality of slots without entering the center hole.
8. The pole base of claim 1, wherein the separate plate is configured to receive a range of multiple sizes of fasteners.
9. The pole base of claim 8, further comprising an oversized washer configured to secure a connection between the separate plate and a fastener from a lower end of the range of multiple sizes of fasteners.
10. The pole base of claim 1, wherein the body comprises a plurality of anti-rotation features.
11. The pole base of claim 10, wherein the plurality of anti-rotation features comprises cavities in a lower portion of the body.
12. The pole base of claim 1, wherein the separate plate comprises one or more mounting projections configured to attach the reinforcing steel to the separate plate when the separate plate is assembled with the body.
13. The pole base of claim 1, wherein the lower portion of each fastener assembly is disposed below an upper surface of the upper portion of the body.
14. A pole base comprising:
a body having an upper portion; and
a pole attachment device disposed on the upper portion of the body, wherein the pole attachment device is a plate having a plurality of slots, the plate having a generally X-shaped outer perimeter and the plate being configured to removeably receive a range of multiple sizes of fastener assemblies such that each fastener assembly may be received in one of the plurality of slots in a plurality of locations along a length of each slot
wherein: the plate comprises a center hole with the plurality of slots oriented radially around the center hole such that a portion of each fastener assembly may pass through the center hole and a fastener shaft of each fastener assembly may pass through the plurality of slots trapping the portion of the fastener assembly under the plate; and a lower portion of each fastener assembly abuts a bottom surface of the plate.
15. The pole base of claim 14, wherein each of the plurality of slots extends through an entire thickness of the plate without reaching any outer periphery of the plate.
16. The pole base of claim 14, wherein the upper portion of the body comprises a recess configured such that the plate sits generally flush with the upper portion of the body when the plate is received in the recess.
17. The pole base of claim 14, wherein:
an opposite pair of the plurality of slots are each configured to receive one of two fasteners; and
the two fasteners, when moving in their respective slots, remain in their respective slots without entering the center hole.
18. The pole base of claim 14, further comprising an oversized washer configured to secure a connection between the plate and a fastener from a lower end of the range of multiple sizes of fastener assemblies.
19. The pole base of claim 14, wherein the portion of each fastener assembly is disposed below an upper surface of the upper portion of the body.
20. A pole base comprising:
a body having an upper portion;
a pole attachment device disposed on the upper portion of the body, wherein the pole attachment device is a plate having a plurality of slots extending through an entire thickness of the plate, each of the plurality of slots being configured to removeably receive at least one fastener assembly in a plurality of locations along a length of each slot; and
reinforcing steel welded directly to an underside of the plate such that the reinforcing steel is contained within the body when the plate is disposed on the upper portion of the body, wherein
the plate comprises a center hole and each of the plurality of slots are radially oriented such that a head or a nut from each fastener assembly may pass through the center hole and a shaft of each fastener assembly may pass through the plurality of slots trapping either the head or the nut under the plate.
21. The pole base of claim 20, wherein a perimeter of the plate is generally X-shaped.

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 medical device for monitoring cardiac function in a patient, comprising:
a plurality of electrodes to deliver cardiac pacing therapy; and
a processor configured to determine a pacing threshold in response to initial delivery of the pacing therapy, determine whether there is a change in the pacing threshold during initial delivery of the pacing therapy, adjust a delivery parameter of the pacing therapy in response to determining the change in the pacing threshold during initial delivery of the pacing therapy, determine whether there is an increase in the pacing threshold during delivery of the adjusted pacing therapy, and determine hypokalemia in response to the increase in the pacing threshold during delivery of the adjusted pacing therapy being present.
2. The medical device of claim 1, wherein adjusting a delivery parameter of the pacing therapy comprises adjusting a pulse width and a rate of delivery of the pacing therapy.
3. The medical device of claim 2, wherein the pulse width is approximately 0.5 milliseconds and the rate of delivery is approximately once per day during initial deliver of the pacing therapy, and the pulse width is approximately 0.06 milliseconds and the rate of delivery is approximately once per hour during delivery of the adjusted pacing therapy.
4. The medical device of claim 1, wherein the determined increase in the pacing threshold during delivery of the adjusted pacing therapy is not equal to the determined change in the pacing threshold during initial delivery of the pacing therapy.
5. The medical device of claim 1, wherein the determined change in the pacing threshold during initial delivery of the pacing therapy comprises a one-step change.
6. The medical device of claim 1, wherein the determined increase in the pacing threshold during delivery of the adjusted pacing therapy comprise a four-step increase.
7. The medical device of claim 1, wherein the determined change in the pacing threshold during initial delivery of the pacing therapy comprises a one-step change and the determined increase in the pacing threshold during delivery of the adjusted pacing therapy comprises a four-step increase.
8. The medical device of claim 7, wherein the pulse width is approximately 0.5 milliseconds and the rate of delivery is approximately once per day during initial deliver of the pacing therapy, and the pulse width is approximately 0.06 milliseconds and the rate of delivery is approximately once per hour during delivery of the adjusted pacing therapy.
9. The medical device of claim 7, wherein adjusting a delivery parameter of the pacing therapy comprises adjusting a pulse width and a rate of delivery of the pacing therapy.
10. The medical device of claim 1, wherein the processor is further configured to determine whether there is a decrease in the pacing threshold during delivery of the adjusted pacing therapy, and determine hyperkalemia in response to the decrease in the pacing threshold during delivery of the adjusted pacing therapy being present.
11. The medical device of claim 1, wherein the processor is configured to generate an alert in response to the determined hypokalemia.
12. A method of monitoring cardiac function in a patient, comprising:
delivering cardiac pacing therapy;
determining a pacing threshold in response to initial delivery of the pacing therapy;
determining whether there is a change in the pacing threshold during initial delivery of the pacing therapy;
adjusting a delivery parameter of the pacing therapy in response to determining the change in the pacing threshold during initial delivery of the pacing therapy being present;
determining whether there is an increase in the pacing threshold during delivery of the adjusted pacing therapy; and
determining hypokalemia in response to the increase in the pacing threshold during delivery of the adjusted pacing therapy being present.
13. The method of claim 12, wherein adjusting a delivery parameter of the pacing therapy comprises adjusting a pulse width and a rate of delivery of the pacing therapy.
14. The method of claim 13, wherein the pulse width is approximately 0.5 milliseconds and the rate of delivery is approximately once per day during initial deliver of the pacing therapy, and the pulse width is approximately 0.06 milliseconds and the rate of delivery is approximately once per hour during delivery of the adjusted pacing therapy.
15. The method of claim 12, wherein the determined increase in the pacing threshold during delivery of the adjusted pacing therapy is not equal to the determined change in the pacing threshold during initial deliver of the pacing therapy.
16. The method of claim 12, wherein the change in the pacing threshold during initial deliver of the pacing therapy comprises a one-step change.
17. The method of claim 12, wherein the increase in the pacing threshold during delivery of the adjusted pacing therapy comprises a four-step increase.
18. The method of claim 12, wherein the change in the pacing threshold during initial deliver of the pacing therapy comprises a one-step change and the increase in the pacing threshold during delivery of the adjusted pacing therapy comprises a four-step increase.
19. The method of claim 18, wherein the pulse width is approximately 0.5 milliseconds and the rate of delivery is approximately once per day during initial deliver of the pacing therapy, and the pulse width is approximately 0.06 milliseconds and the rate of delivery is approximately once per hour during delivery of the adjusted pacing therapy.
20. The method of claim 18, wherein adjusting a delivery parameter of the pacing therapy comprises adjusting a pulse width and a rate of delivery of the pacing therapy.
21. The method of claim 12, further comprising generating an alert in response to the determined hypokalemia.
22. The method of claim 12, further comprising:
determining whether there is a change in the pacing threshold during initial delivery of the pacing therapy;
adjusting a delivery parameter of the pacing therapy in response to determining whether there is a first decrease;
determining whether there is a second decrease in the pacing threshold during delivery of the adjusted pacing therapy; and
determining hyperkalemia in response to the second decrease in the pacing threshold being present
23. A non-transitory computer-readable medium for storing a set of instructions for performing a method, the method comprising:
delivering cardiac pacing therapy;
determining a pacing threshold in response to initial delivery of the pacing therapy;
determining whether there is a change in the pacing threshold during initial delivery of the pacing therapy;
adjusting a delivery parameter of the pacing therapy in response to determining the change in the pacing threshold during initial delivery of the pacing therapy being present;
determining whether there is an increase in the pacing threshold during delivery of the adjusted pacing therapy; and
determining hypokalemia in response to the increase in the pacing threshold during delivery of the adjusted pacing therapy being present.