text:
|Publication number
|Publication type
|Application number
|Publication date
|Oct 29, 1985
|Filing date
|Feb 22, 1984
|Priority date
|Oct 5, 1981
|Fee status
|Publication number
|Michael E. Garabedian, Robert E. Roehrs
|Original Assignee
|Alcon Laboratories, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (7), Non-Patent Citations (25), Referenced by (132), Classifications (9), Legal Events (8)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation-in-part of Ser. No. 308,386, filed Oct. 5, 1981 now U.S. Pat. 4,443,432, issued Apr. 17, 1984.
The present invention relates to electrolyte solutions for use within the human body and more particularly to solutions useful for irrigating tissues during surgery.
Any scission into the human body is detrimental to the human body and invariably results in cell loss. The need to keep cell loss to a minimum is particularly crucial during any surgical procedure performed on delicate and irreplaceable tissues, such as the tissues of the eye, nerves, etc.
The cornea of the eye is comprised of five layers: epithelium, Bowman's membrane, stroma, Decemet's membrane, and endothelium. The endothelium layer is particularly vulnerable to trauma as the endothelial cells are infrequently, if ever, replaced as a normal process in the adult life. The endothelium is principally responsible for the maintenance of the proper state of hydration of the stromal layer. The stromal layer has a tendency to imbibe fluid, a tendency which is counterbalanced by outward fluid transport via the endothelium. If the proper fluid balance is not maintained in the stromal layer, the cornea thickens and the characteristic transparency of the cornea is lost. Accordingly, cell loss or damage in the endothelial layer will result in decreased vision. Failure of the endothelium to perform its fluid transport function for short periods of time will result in corneal thickening and visual clouding. Because of the importance of, and the vulnerability of, the endothelial layer, it is necessary during eye surgery, such as cataract and retinal surgery or corneal transplants, to make provisions for the protection of the endothelial cells.
A significant factor causing cell loss during tissue scission is the traumatic change in environment experienced by the internal cells. Exposure to the atmosphere presents a far different environment for the cells than is provided by the natural fluids in which they are bathed. To simulate the natural cellular environment and thereby prevent cell damage, exposed tissue during surgery is frequently irrigated in solutions which attempt to approximate natural body fluids. The value of bathing eye tissue during surgery to prevent cell damage has long been recognized. For internal ocular tissues, such as the endothelium, the aqueous humor is the natural bathing fluid and, hence, an ophthalmic irrigating solution to protect the endothelium should as closely as possible resemble the aqueous humor.
Of primary concern in a tissue irrigating solution is that the osmolality of the solution be generally isotonic with cellular fluids so as to maintain equal osmotic pressure within and without the cell membranes. To this end, one of the early ophthalmic irrigating solutions was isotonic (0.9%) saline. However, as has long been recognized, isotonic saline is quite inadequate as an opthalmic irrigating solution and has been shown to result in endothelial cell swelling, cell damage, and consequent corneal clouding.
Because of the inadequacy of isotonic saline, various alternative electrolyte solutions have been proposed as ophthalmic irrigating solutions in attempts to provide solutions which more closely resemble the aqueous humor and prevent cell damage and corneal clouding. Standard electrolyte solutions primarily intended for injection solutions, such as Ringer's solution and lactated Ringer's solution, have been used as ophthalmic irrigating solutions because of their wide availability as sterile solutions.
A solution intended for ophthalmic irrigation known as balanced salt solution (BSS) has also been developed. BSS contains the essential ions, calcium, sodium, potassium, magnesium and chloride in generally optimal concentrations for ocular tissue, and has an acetate-citrate buffer system which is compatible with divalent calcium and magnesium ions.
The various electrolyte solutions used for ophthalmic irrigation have been improvements over normal saline by providing necessary ions in addition to Na+ and Cl- as provided by isotonic saline. Mg++ is an important cofactor for adenosine triphosphatase, an enzyme which plays an important role in mediating the fluid transport pump in the eye. Ca++ is necessary to maintain the endothelial junction. K+ is an important factor in many biochemical processes, and the fluid transport pump of the endothelium requires a proper Na+ /K+ ratio. The previously known electrolyte solutions used to irrigate ocular tissue have reduced but not eliminated corneal swelling and cell damage.
The need for improved ophthalmic irrigating solutions continues, particularly in view of new surgical techniques which may probe deeper into the eye and require several hours of operating time. Surgical advances now permit surgery in the vitreous (posterior) chamber to remove opacified vitreous humor or to repair retinal detachment. Such operations require significant time, e.g., 1 to 3 hours, and large volumes of irrigating solution, e.g., 100-1000 ml.
During eye surgery and particularly during surgery which requires extended periods of time, proper electrolytic balance alone is insufficient to retain normal corneal thickness. To maintain proper corneal thickness and prevent cell damage, an irrigating solution in addition to electrolytic balance must provide metabolic support and must particularly provide factors needed for the enzyme-mediated Na+ /K+ pump system through which excess fluid is removed from the stroma.
To incorporate factors necessary for sustained metabolism by endothelial cells, glutathione-bicarbonate-Ringers solution (GBR) was developed in which NaHCO3, glutathione, dextrose and adenosine (an optional ingredient) are added to Ringer's solution. Bicarbonate, dextrose and glutathione have been shown to be important factors in maintaining structural integrity of endothelial cells. The aqueous humor has a bicarbonate buffer system. Dextrose (d-glucose) provides a substrate for various metabolic pathways, and glutathione has been shown to aid the metabolic pump mechanism by maintaining proper Na+ /K+ adenosine-triphosphatase. GBR has been shown effective in maintaining corneal thickness and endothelial cell integrity for up to three hours.
While the effectiveness of a GBR ocular irrigating solution has been shown both in vivo and in vitro, its use in surgery has been limited for reasons of stability and sterility. It is to be appreciated that sterility of an ophthalmic irrigating solution is absolutely essential. To insure sterility, it is desirable that an irrigating solution be prepackaged so that the quality and sterility may be closely monitored and tested as contrasted with an extemporaneously mixed solution as might be prepared in a hospital pharmacy. The solution will perfuse the eye in essentially a closed system where even a small number of organisms could produce an overwhelming endophthalmitis, as pseudomonas is one of the very few organisms that has very few metabolic requirements and can grow with a minimal nutrient supply such as phosphate and bicarbonate. Dr. Jan Worst has reported on a series of infections in Europe with pseudomonas-contaminated irrigating solutions. (January 1978, American Intraocular Implant Society Journal).
GBR may not be prepackaged due to the long term incompatability and/or instability of its various moieties. Of the moieties added to Ringer's solution to formulate GBR, bicarbonate is perhaps the most important (McEnerney et al. Investigative Ophthamology and Visual Science 16 No. 7, July 1977). Unfortunately the bicarbonate as well as the phosphate in a bicarbonate-phosphate buffer system form insoluble precipitates with Mg++ and Ca++. While at the ionic concentrations useful in ophthalmic irrigation, precipitation is not a problem in freshly prepared solution, long-term storage is proscribed. As insoluble crystals introduced into the eye will cloud vision, the importance of keeping a tissue irrigating solution free of insoluble precipitates may be readily appreciated. A Ringer's solution fortified with sodium bicarbonate and dextrose and injected in an Ocutome� Fragmatome™ instrument deposits pure crystals of calcium bicarbonate in the instrument system. Similar crystals are deposited during surgery inside the eye on the retina, vitreous disk, iris and on exposed uvea or sclera. (Dr. Connor O'Malley, "Salt Contamination of the Eye--An Infusion Hazard". Ocutome/Fragmatome Newsletter, 4, No. 4, 1979).
Complicating the maintenance of GBR's stability is the fact that the pH of GBR will gradually increase due to the inadequacy of the bicarbonate-phosphate buffer. To provide proper pH, i.e., about 7.4, the pH must be monitored and adjusted with CO2 immediately prior to use and even during use. The chances for contamination during pH adjustment are great.
A further factor which proscribes long-term storage of GBR is the unavailability of a proper pH at which all of the moieties are stable. Several moieties of GBR are unstable at the physiological pH of about 7.4. Below a pH of about 8, bicarbonate generally decomposes to CO2, resulting both in a loss of bicarbonate concentration and increased pH. On the other hand, glucose stability requires a pH of less than about 6. Glutathione, while biologically effective either in reduced or oxidized form, is preferred in the oxidized form because the reduced form quickly oxidizes in aqueous solutions, preventing proper labeling of the irrigating solution. Oxidized glutathione (glutathione disulfide) is unstable over extended periods of time at a pH of above about 5. The concentration of glutathione may also decrease to an unacceptable concentration when stored over long periods of time in admixture with all other components. Because of the demonstrated efficacy of GBR as an ocular irrigating solution, it would be desirable to provide a formulation which contains the essential factors found in GBR and which may be stored in a sterilized form for use in eye surgery.
Accordingly, it is a primary object of the invention to provide a stable sterile ophthalmic irrigating solution which, in addition to correct electrolyte balance, provides factors necessary for continued metabolism in the endothelial cells, maintenance of the fluid transport pump system, and consequential maintenance of proper corneal thickness and clarity.
Neurosurgery is another important area where there is a need for irrigating solutions which better stabilize irreplaceable tissue. It is well known that destroyed nerve cells, for the most part, are not regenerated. Normal saline is the traditional wound irrigating solution used in neurosurgery, at least partially because of its low cost and ready availability. However, the use of saline has several theoretical disadvantages which may be of unrecognized clinical importance. The pH of saline ranges from 5-7 and is unbuffered; therefore, it causes an acid environment. In the absence of circulating cerebrospinal fluid, as is usually the case in open neurosurgical procedures, this acid pH may cause damage to the exposed brain and spinal cord.
It is another primary object of the present invention to provide an irrigating solution that stabilizes neuro tissue and other sensitive tissues.
Two separately prepared solutions are provided that when mixed together provide an irrigating solution which has important benefits for irrigating tissue during surgery, particularly irreplaceable tissue such as ocular tissue or neuro tissue. One of the solutions is basic and contains bicarbonate ions and preferably phosphate ions. The other solution is acidic and contains calcium and magnesium ions. Dextrose is provided in one of the solutions, preferably the acidic solution. Glutathione is provided in one of the solutions, preferably the acidic solution. Sodium, potassium and chloride ions are each provided in at least one of the solutions. The mixed irrigating solution is sufficiently stable for surgical use within about 24 hours of preparation but unstable for long-term use. The segregation of the components into the two partial solutions, which are each stable for extended periods of time, overcomes the inherent longterm stability problem of the irrigating solution.
The present invention is directed generally to a two-part solution system which includes a basic solution and an acidic solution. The composition and concentration of the two solutions are such that they are individually stable and may be separately stored for long periods. When mixed together the two solutions form a tissue irrigating solution that may be used for surgery during the next 24 hours. The mixed solution is useful for occular surgery as it contains the necessary factors to maintain endothelial cell, integrity and corneal thickness during ocular surgery. It is further found that the same factors are important in maintaining the stability of other sensitive tissues, including nerve tissue. The combined irrigating solution contains the necessary ions for tissue stability, Ca++, Mg++, Na+, K+ and Cl- in a bicarbonate-phosphate buffer as well as oxidized glutathione and dextrose. As used herein, "glutathione" is used to refer to either the oxidized form of glutathione (GSSG) or the reduced form (GSH). Irrespective of the form used to prepare the solution, the glutathione will be in its oxidized form in the final mixed solution to avoid confusion in labeling, and the solutions will generally be prepared with oxidized glutathione. The solution may also contain adenosine.
The electrolytes are provided in proportions conducive to cellular integrity and continued cell metabolism. Preferably the proportions of electrolytes resemble BSS, a solution particularly formulated for ophthalmic irrigation rather than Ringer's solution, which was formulated for injection into the cardiovascular system. Preferably the irrigating solution is more substantially buffered than GBR so that the pH does not continually change as does the pH of GBR. However, it is intended that the scope of the present invention be limited only to proportions of electrolytes compatible with body tissues.
The irrigating solution contains from about 130 to about 180 mM/l Na+, from about 3 to about 10 mM/l K+, from about 1 to about 5 mM/l Ca++, from about 0.5 to about 4 mM/l Mg++ and from about 130 to about 210 mM/l Cl-. To maintain osmotic stability of the cells, the osmolality is between about 250 and about 350 mOsm and preferably about 290-320 mOsm. So as to closely match the physiological pH of 7.4, the pH of the final irrigating solution is between about 6.8 and about 8.0 and preferably about 7.2-7.8. To maintain the fluid pump system, the bicarbonate concentration in the combined irrigating solution is between about 10 and about 50 mM/l. To stabilize the pH, an additional buffering agent is provided. Preferably the buffering agent is phosphate which is provided in sufficient quantity so that final phosphate concentration of the irrigating solution is between about 1 and about 5 mM/1. The final irrigating solution contains between about 2 and about 10 mM/l glucose and between 0.03 and about 0.5 mM/l of oxidized glutathione or the equivalent amount of reduced glutathione. One mole of oxidized glutathione is the equivalent of two moles of reduced glutathione.
The basic solution provides the phosphate and bicarbonate buffering moieties, preferably in the form of dibasic sodium phosphate and sodium bicarbonate. The pH of the basic solution is adjusted to about the physiological pH, of 7.4, preferably to between about 7.2 and about 7.8. As hereinbefore mentioned, the pH of a bicarbonate-containing solution is preferably above about 8.0 to prevent decomposition of the bicarbonate. It has been found, however, that the bicarbonate may be stabilized if it is added to a solution with a pH of above about 8 and thereafter adjusted to a pH between 7 and 8. Accordingly, when the basic solution is prepared, Na2 HPO4 is added prior to the addition of NaHCO3 so that NaHCO3 is dissolved in a solution with a pH of between about 8 and about 9. The solution is thereafter adjusted with dilute acid, such as H2 SO4, H3 PO4 or HCl, to the desired final pH of the basic solution. Alternatively, carbon dioxide may be added to adjust the pH.
Potassium and additional sodium are provided in the basic solution in the form of sodium and potassium salts, such as sodium or potassium chlorides, sulfates, acetates, citrates, lactates, and gluconates. The sodium and potassium are compatible with all of the moieties present in the finished tissue irrigating solution, and sodium chloride and potassium chloride may be added to either solution or divided between the solutions. However, in view of the fact that the basic solution provides the buffer system, the pH of the final irrigation solution may be more accurately determined if all compatible salts are included in the basic solution.
The acidic solution provides the Ca++ in the form of calcium chloride, the Mg++ in the form of magnesium chloride, the glutathione and the dextrose. The pH is adjusted to below about 5 to provide long-term stability to the dextrose and oxidized glutathione.
Because of the requirement that the acidic solution have a low pH, it is preferable that the volume of the basic solution greatly exceed the volume of the acidic solution and that the acidic solution contain no buffering agents. The acidic solution may be adjusted below a pH of about 5 with a relatively small amount of HCl. Because the acidic solution is unbuffered, its pH is a reflection of the acid concentration and less acid is needed to adjust the pH of a small volume. The large volume of buffered basic solution may be adjusted very close to the final pH of the irrigating solution and will be relatively unaffected by the addition of the small volume of the acidic solution. Preferably, the ratio of the basic solution volume to the acidic solution volume is about 10 to 1 to about 40 to 1.
The basic solution and the acidic solution are sterilized and separately bottled or contained under sterile conditions by standard techniques, such as autoclaving, or use of sterilizing filters, but preferably by heat sterilization. Typically, the basic solution, which preferably contains only inorganic moieties, is autoclaved, whereas the acidic solution, which preferably contains the organic components, is microfiltered. To avoid the need for measuring volumes in the hospital which may introduce possible error and/or contamination, it is highly preferred that particular volumes of the basic and acidic solutions be bottled so that adding the entire content of a container of the acidic solution to the entire content of a container of the basic solution results in the correctly formulated tissue irrigating solution. The solutions may be mixed up to 24 hours before a surgical procedure without the occurrence of significant pH change and without the formation of detectable precipitates and without degradation.
Precautions to maintain sterility of the solutions and to insure correct mixing of the acidic and basic solutions cannot be overdone. While the manufacturer may take all due precautions to maintain quality control, carelessness by a technician may render all such precautions for naught. Any opening of a container, no matter how carefully performed, increases the likelihood of contamination in the contents. As one method of substantially eliminating the possibility of improper mixing and to reduce the likelihood of contamination, the solutions may be shipped in a container having a first chamber for the basic solution, an isolated second chamber for the acidic solution and means to communicate the chambers without opening the container. The use of such containers are known for the shipment of multi-part medical solutions. As one example, a container may have a lower chamber containing a measured volume of the basic solution separated by a membrane from an upper chamber containing a measured volume of the acidic solution. The container cap may include a plunger means which, when depressed, causes a sharp point or blade depending therefrom to break the membrane. The container is thereafter agitated, as by shaking, to complete the sterile mixing in proper volume of the acidic and basic solutions.
The proper mixing of the acidic and basic solutions may also be carried out by aseptically removing the acidic solution from its package with a sterile syringe and needle and aseptically adding the acidic solution to the contents of the basic solution package through the rubber stopper. Alternately, a sterile double-ended needle can be used to transfer the acidic solution to the basic solution by aseptically inserting one end of the needle into the vial containing the acidic solution and then aseptically inserting the other end of the needle into the basic solution package, whereby the vacuum that is maintained therein transfers the acidic solution to the basic solution and is mixed.
The two-part solution of the present invention also provides an advantage as to safety if a technician should fail to properly mix the two solutions. The larger volume basic solution is physiologic so that there is less chance of toxicity if the basic solution were used without the acidic solution being mixed therewith.
The manner of providing an irrigating solution which is sterile and storable, and which provides the correct electrolyte balance as well as factors necessary for cell metabolism may now be fully appreciated. By segregating the phosphate and bicarbonate ions from the divalent magnesium and calcium ions, the buildup of insoluble precipitates is eliminated. The solution that contains the bicarbonate is slightly basic and the bicarbonate therein is stabilized as a result of initially dissolving the bicarbonate at a sufficiently basic pH. The other solution is sufficiently acidic to stabilize dextrose and oxidized glutathione. The basic and acidic sterile solutions are simply combined to provide the correctly formulated irrigating solution without adding further substances, adjusting the pH or intoducing apparatus, any of which are potentially contaminating. While the final combined irrigating solution is not stable for an extended period of time, it is stable for sufficiently long periods, i.e., 24 hours, so that the irrigating solution may be carefully mixed under unhurried conditions prior to an operation and remain stable throughout the operation. The buffer system is adequate to maintain a generally constant pH for at least a 24-hour period, eliminating the need to monitor or adjust the pH.
Separate sterile basic and acidic solutions were made and packaged. A sample of the basic solution and a sample of the acidic solution were mixed, and the combined solution was tested for stability as well as the ability of maintaining the structural integrity and function of rabbit and human endothelia during in vitro perfusion, i.e., simulating intraocular irrigation.
Part I (basic solution) was made by dissolving 2.582 Kg sodium chloride, 138.2 grams potassium chloride, and 151.55 grams anhydrous dibasic sodium phosphate in water for injection at about 20� C. Then 918.75 grams of sodium bicarbonate where added and dissolved. Additional water for injection was added to make about 350 Kg batch weight and 1N HCl added (about 1 liter) to adjust pH to about 7.4. The solution was then passed through a 0.45 micron Millipore filter and each bottle (USP Type I glass) was filled with about 480 ml of solution. The filled bottles were then stoppered, vacuumed and sealed. The sealed bottles were sterilized by autoclaving at 121� C. for about 23 minutes.
Part II (acidic solution) was made by dissolving 385 grams calcium chloride dihydrate, 500 grams magnesium chloride hexahydrate, 2300 grams dextrose, and 516 grams of 94% oxidized glutathione (glutathione disulfide) in water for injection to make a final batch volume of about 100 liters. The solution was then sterile filtered through a 0.22 micron membrane filter and aseptically filled into presterilized 20 ml Type I glass vials and sealed with presterilized rubber stoppers. (Alternately, the solution can be packaged in Type I glass ampules.)
After adding 20 ml of Part II (acidic solution) to a 480 ml bottle of Part I (basic solution) and mixing, in vitro corneal endothelial perfusion studies were carried out on both rabbit and human donor corneas along with commercial lactated Ringer's solution and Plasmalyte 148 (pH 7.4) for comparison. Corneas from rabbits and human donor corneas were excised and mounted in a dual chambered specular microscope. A swelling rate (u/hr) was calculated by regression analysis from measurements of sequential changes in corneal thickness. Isolated corneas were perfused at 37� C. at 15 mm Hg with each of the test solutions for up to three hours. Each experiment was studied as a pair, one cornea receiving the tissue irrigating solution of the instant invention and the other cornea perfused with either lactated Ringer's solution or Plasma lyte. The corneal epithelium in all rabbit experiments was intact and covered with medical grade silicone oil. In the human corneas, the epithelium was debrided prior to mounting in the specular microscope. At various times during the course of the perfusion, the corneas were fixed for scanning and transmission electron microscopy in 2.7% glutaraldehyde and phosphate buffer (pH 7.2, 330 mOsm) for at least eight hours at 4� C. They were then post fixed in 2% osmium tetroxide for one hour and embedded in a low viscosity epoxy medium. For scanning electron microscopy (SEM), the resin was washed off the endothelial surface of a portion of each cornea according to the modified method of Cleveland and Schneider, "A Simple Method Preserving Ocular Tissue for SEM," Vision Research 9, pp. 1401-1402, 1969. After polymerization of the tissue specimens overnight at 37� C. and for 48 hours at 60� C., the tissue was glued to SEM specimen stubs coated rotationally with carbon and gold palladium metal and viewed with an AMR (1000) scanning electron microscope. Endothelial perfusion of tissue irrigating solution of the instant invention to the rabbit cornea resulted in a swelling rate of 0.001 u/hr. On ultrastructural examination, the endothelial cells of all corneas were intact with normal cell morphology maintained throughout the three-hour period.
In the paired corneas, the endothelium was perfused with Plasmalyte 148 (ph 7.4). There was marked corneal swelling at a rate of 84.5 N/hr. Upon ultrastructural examination with SEM, the endothelial cells appeared to be separating at the junctions between cells, and on transmission EM, the cells were balled up and the junctions broken. In some corneas that were perfused with Plasmalyte, complete junctional breakdown occurred and the endothelial cells balled upon Descemet's membrane.
The paired corneas that were perfused with lactated Ringer's solution had a swelling rate of 32.7 u/hr. On ultrastructural examination, the cells were morphologically swollen and there appeared to be breaks in the outer plasma membrane. Cytoplasmic bleebing was apparent on the outer surface of the corneal endothelial cells and on transmission electron microscopy there was dilation of the endoplasmic reticulum, condensation of the mitochondria and microfilament network along the outer plasma membrane. Associated with the cytoplastic changes, there was also edema of the endothelial cells adjacent to Descemet's membrane.
Endothelial perfusion of human corneas with tissue irrigating solution of the instant invention had a negative swelling rate of 24.6 u/hr. and, upon ultrastructural examination, the endothelial cells were shown to be intact, the junctions intact, and the cell organelles normal by transmission electron microscopy. The paired corneas that were perfused with Plasmalyte all showed junctional breakdown between the individual cells and balling of the endothelial cell. These ultrastructural changes were associated with a corneal swelling of 19 u/hr.
By comparison, the paired corneas that were perfused with lactated Ringer's solution showed a slight deswelling of only -5 u/hr. but there were associated ultrastructural changes in the surface morphology of the corneas of older humans. Junctional breakdown was apparent, and balling of the cells and nucleus with marked vacules in the cytoplasm occurred. However, the cell organelles within the endothelium appeared normal.
The data obtained in this study indicates that Plasmalyte 148, an IV electrolyte solution used for phacoemulsification, caused corneal endothelial cell breakdowns and functional disruption of the endothelium during in vitro perfusion and therefore may cause corneal edema after phacoemulsification. The data obtained also indicates that the tissue irrigating solution of the instant invention maintains human and rabbit corneal function and ultrastructural integrity for a three-hour period.
By comparison, lactated Ringer's solution is only able to maintain the corneal endothelial cell integrity and ultrastructural appearance to variable degrees both in rabbits and in humans and may be adequate for short-term irrigation of the cornea, but will provide, at the very best, minimal protection to the corneal endothelium when perfused to the endothelium for extended periods of time.
The effects of continuous irrigation with the tissue irrigating solution and with 0.9% saline on the cerebral cortex of the cat has been compared. Tissue irrigating solution in accordance with the present invention was freshly mixed as per Example 1. The composition of the tissue irrigating solution is compared with isotonic saline and cerebrospinal fluid in Table 1 below:
TABLE 1______________________________________ IrrigatingCerebrospinal Solution 0.9% normalfluid meq/L* meq/L** saline meq/L______________________________________Na.sup.+ 145.0 150.7 154K.sup.+ 3.0 5.1 0Mg.sup.++ 2.2 2.0 0Ca.sup.++ 2.3 2.1 0H.sub.2 PO.sub.4.sup.- 1.0 3.5 0Cl.sup.- 125.0 131.4 154HCO.sub.3.sup.- 24.0 25.0 0pH 7.35 � .1 7.2 � .4 6.0 � 1.0Osmolality 306 � 10 305 � 15 290______________________________________ *Diem et al., Documenta Geigy Scientific tables, Basle, Switzerland: CibaGeigy Limited, 1972, p. 523. **Irrigating Solution also contains 2 nonionic components: 5.1 mmol dextrose and 0.28 mmol oxidized glutathione
The subjects were six adult mongrel cats. The animals were anesthetized with Surital� and atropine and were maintained on animal ventilators. Intravenous and intra-arterial catheters were placed via a femoral cut-down. Blood pressure, temperature, and arterial blood gases were monitored. Bilateral craniectomies were performed and the dura and arachnoid elevated from the cortex using microsurgical technique. Three in-line platinum disc electrodes were placed laterally on the exposed cortex to measure evoked potentials, which were recorded on a Clinical Technology Corporation Model 2000 averaging computer. pH was monitored bilaterally using Microelectrodes Inc., pH electrodes number 408C and standard Beckman pH meters. Local cerebral blood flow was monitored using hydrogen clearance methods, which have been described elsewhere. C. Myklebust et al., IEEE Trans BME 28(3) 265-267 (1981).
Immediately following exposure of the cortical surface, continuous drip irrigation was initiated using small bore needles at a rate of 15 cc/hr, to saturate the cortical surface. 0.9% saline was used on one side and the irrigating solution on the other for a minimum of 4 hours in each animal.
Surface pH, evoked potentials and local cerebral blood flow were measured at regular intervals throughout the trials. In four animals, shortly prior to termination of the trial, Evan's blue dye was injected intravenously and the cortical surface examined under magnification for evidence of extravasation, indicating blood-brain barrier injury.
In two animals, after the minimum 4 hour recording period, the animals were allowed to become hypoxic for a 5 minute period of time in order to evaluate the additional factors of anoxia and/or ischemia on the parameters measured. These parameters were recorded at very short intervals for 3 hours following the episode.
Changes in surface pH as a function of time are depicted in Table 2 below:
TABLE 2______________________________________ pH pHHrs. Saline Irrigating Solution______________________________________0 7.4 7.31/2 7.4 7.21 7.4 7.111/2 7.3 7.32 7.2 7.221/2 6.9 7.33 6.8 7.331/2 6.8 7.34 6.6 7.3______________________________________
Marked depression in pH was seen at 11/2 to 21/2 hours with saline irrigation. Changes in pH related to saline irrigations became statistically significant at approximately 2 hours (F=2.9). This had increased markedly at the 4 hour termination point, (F=21.3). No significant changes in pH were seen with the tissue irrigating solution. The pH differences between normal saline and the irrigating solution became significant at the 21/2 hour point (F=4.59) and had more than doubled by termination of the trial (F=11.2).
In the trials with induced hypoxia, decreases in pH were seen at both sides but were more marked on the saline irrigated surface. These changes resolved over the three-hour measurement period at the irrigating solution surface; on the saline side, the pH continued to decrease. Gross brain swelling occurred bilaterally along with the post-hypoxia pH changes; this resolved coinciding with the pH changes on the irrigating solution surface, but remained unchanged on the saline side.
Blood-brain barrier changes were prominent in 3 of the 4 animals injected with Evans blue dye. There was no dye extravasation on the irrigating solution surfaces, except in one animal with a small pial tear. Changes were marked on the saline sides, with multiple areas of breakdown in two, and confluent dye extravasation in the third.
These findings tend to substantiate that the irrigating solution represents an improvement for neurosurgical procedures, primarily because it is buffered with HCO3 and contains glucose and glutathione. The pH changes observed with normal saline were dramatic; while the extent of injury to the nervous system produced is difficult to assess, its existence certainly can be strongly suspected. In addition to dysfunction of enzyme activity and alteration of electrical potentials causing abnormalities of conduction, it is conceivable that secondary ionic shifts might occur at the neuronal level. Swiontek et al., Surg Neurol 14: 365-369, (1980) have suggested that severe pH changes often represent secondary manifestations of nervous tissue injury.
The changes in the blood-brain barrier were also prominent. It has been observed that the blood-brain barrier is maintained by the endothelial tight junctions; these in turn, are maintained by ionic charges. Several investigators have emphasized that the production of cerebral edema is related to the breakdown of the blood-brain barrier with gaps occurring at the level of the tight junction related to increased permeability. The lack of changes in the blood-brain barrier status may be related to preservation of the endothelial tight junction by the calcium bicarbonate buffer present in the irrigating solution.
Of particular interest were the subjects in which short periods of hypoxia were induced. In both instances, marked pH decreases were seen immediately following the episode. These persisted and became worse on the surfaces irrigated with normal saline. However, on the BSS Plus side, recovery of the pH almost to baseline, was seen in both animals. Additionally, the edematous changes which were seen shortly after the hypoxic episode resolved on the irrigating solution irrigated cortex. While it is impossible to establish a mechanism on the basis of these two trials perhaps reestablishment of the endothelial tight junctions assisted in the resolution of the edema. In one of these two trials, the blood-brain barrier changes were particularly prominent on the normal saline side, with a confluent field of disruption.
These results show that the irrigating solution of the invention represents an improved irrigating solution for neurosurgical procedures.
The usefulness of the two-part tissue irrigating solution has been illustrated by way of example with reference to two very critical types of tissues, ocular tissue and neuro tissue. However, the components of the irrigating solution which are important in stabilizing these tissues are important in stabilizing other tissues, and the desirability of having such a solution without the need to prepare it extemporaneously apply to other surgical applications as well. Examples of where the irrigating solution is useful include irrigating vessels in microvascular surgery and in organ transplants; graft sites in burn-graft procedure; joint space in any major orthopedic procedure, e.g., hip or knee replacement, ear canal during ear, nose and throat surgery, the pulmonary tree in bronchoscopy procedures, the peritoneal cavity during abdominal surgery, heart chambers during open heart surgery, saphenous veins during coronary artery by-pass surgery, the uterus in gynocology surgery, e.g., a D & C, and the bilary tree or pancreatic drainage ducts in pancreatobiliary surgery. This list is by no means exhaustive and is not intended to limit the present invention.
While the whole invention has been described in terms of preferred embodiments, modifications obvious to one skilled in the art may be without departing from the scope of the present invention which is limited only by the following claims:
|Cited Patent
|Filing date
|Publication date
|Jul 21, 1972
|Jun 28, 1974
|Cybersal Inc
|Therapeutic composition
|Jul 26, 1971
|Oct 22, 1974
|Flow Pharma Inc
|Eye solution and method of using same
|Nov 27, 1972
|Apr 22, 1975
|Process for producing a therapeutic composition
|Jul 21, 1972
|Jul 29, 1975
|Method for administering water soluble drugs, nutrients and other solutes to a mammal
|Dec 13, 1974
|Aug 31, 1976
|Chemo Drug Company
|Electrolyte solutions containing magnesium and free bicarbonate ions
|Sep 29, 1978
|Dec 9, 1980
|Peyman Gholam A
|Intraocular infusion irrigation solution and method
|Oct 5, 1981
|Apr 17, 1984
|Alcon Laboratories, Inc.
|Ophthmalic irrigating solution
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|Feb 6, 1984
Owner name: ALCON LABORATORIES, INC., FORT WORTH, TX A CORP. O
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When God isn't changing your circumstance.
Lord I bring to you my burdens and you know my situation. You know I cant make it without you. Comfort my heart, give me strength & help me carry on. My daily prayer.
Try our glute workout for a toned butt! This full routine includes squats, strength training, and a cardio Stairmaster workout! - Tap the pin if you love super heroes too! you will LOVE these super hero fitness shirts!
Cardio and Strength Workout frugal fitness tips, thrifty fitness tips
This asana is also known as the Scorpion Pose. It requires both core and shoulder strength. It is an extremely challenging yoga asana. 1 Yoga Tip For a Tiny Belly.

subset: commoncrawl


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Aren't they adorable?
Gwen Stefani, 46, was accompanied by Blake Shelton, 39, at the 2016 Radio Disney Music Awards — and the country singer couldn't help but pack on the PDA before his ~honey bee~ went up to accept this year's Hero award.
RELATED: See the Cover Art For Blake Shelton's New Album 'If I'm Honest'
(Photo Credit: Disney Channel)
"I never thought I would make a difference. So, I'm so honored to be here. I'm so happy to be making music. I'm so blessed to make music and share it with you and to receive your love back. I am so healed by you," Gwen said during her acceptance speech.
The Voice costars confirmed their relationship in November shortly after their respective divorces — and since then went on to record a duet together, called "Go Ahead and Break My Heart," off Blake's upcoming album, If I'm Honest.
Gwen starts her tour with Eve this month for her latest album, This is What the Truth Feels Like.


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Nicolette Raynaud. Dining room. June 12th , 2017.
When it comes to centerpieces, many design enthusiasts enjoy switching out arrangements with each new season. For example, why not go tropical for the upcoming summer months? With an abundance of amazing centerpiece ideas to choose from, affordable and eye-catching options are at the ready. Take a chance on a new design, and enjoy the fruits of your labor!
Combining a chic, compact and efficient dining area with the kitchen is the modern trend. As the kitchen island often doubles as an informal gathering spot, there is little need for an expansive alternative. With designers offering some ultra-cool tables that allow you to play with different themes, shades and styles, small dining rooms and dining areas represent a hip trend that is here to stay.
Sure, we've showcased a few va-va-voom centerpieces that make a dramatic statement. But a surprisingly large number of striking dining table centerpieces are simple, elegant and easy to reproduce. This is good news for those of us who are on a budget or who simply change our minds often and want the flexibility of switching out one centerpiece for another on a whim. Check out the diverse array of ideas below:
One increasingly popular design trend is the use of a bold pendant light as the ultimate dining room statement. In fact, when the light hangs low enough, sometimes it becomes a substitute centerpiece. What table trinkets could possibly compete with the circular-motif pendant light below, shown hanging over the Mille dining table by Bonaldo?
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Apollo Hospitals Enterprise Ltd has posted a decline of 22.9 per cent in net profit at Rs 70.90 crore during the quarter ended September 30, 2017, as compared to Rs 91.99 crore during the same quarter of last year. The total income grew to Rs 1,854.27 crore during the quarter as against Rs 1,643.54 crore during the corresponding quarter of last year.
"It has been a good quarter where we have seen an overall recovery in volumes. It also reiterates the resilience of our model, powered by a strong focus by clinical and operational excellence," said Akhileswaran Krishnan, Chief Financial Officer of Apollo Hospitals. Overall the performance has been good for this quarter, he said.
The 23 per cent drop in PAT was as expected, due to higher depreciation and interest costs for the year, following investments in new hospitals. The company added almost 13 new hospitals at a capex worth over Rs 2,000 crore. All of these will start contributing to the business shortly. Some have already started contributing, Krishnan said.
The new hospitals have already seen steady growth this year. The Navi Mumbai hospital, however, posted a loss of Rs 10 crore during the quarter (Rs 15 crore in the year-ago quarter). Despite this, the Ebitda of the new hospitals combined has been Rs 9 crore positive, compared with a negative figure in the first quarter of the year, Krishnan said. Between the first and second quarters of this fiscal year, the company posted a 15 per cent increase in volume.
"Our Ebitda went up 31 per cent between the first and second quarters of this year," Krishnan added. While the Ebitda during the quarter declined by 0.3 per cent to Rs 212.2 crore from Rs 221.9 crore, it has been flat between last year and the current year. Apart from the loss in Navi Mumbai unit, the company has been absorbing Rs 10 crore every quarter towards stent cost. The implementation of Goods and Services Tax has also delivered a Rs 5 crore loss during the reporting quarter.
"Year on year we have delivered 11 per cent growth in healthcare services, our standalone pharmacies for the quarter have grown by 23 per cent, of which only 17 per cent has been recorded, since that is normalised for GST," said Krishnan. The revenue of existing hospitals was up six per cent while new hospitals grew by 36 per cent to Rs 368.2 crore during the first half of the fiscal.


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On one hand, customers want more email but immediately reject anything that is not personalized, relevant or timely enough. While email is seen as increasingly credible by consumers, it is proportionately as difficult to catch audience attention with email that lacks intelligence in the context of personalization or relevance. These are the findings from Adobe's third annual email survey (of US white collar workers' email usage preferences).
Brands have to strike the right balance between customer expectations and customer experience, and enable it with the right email marketing tools and technology. In this context, Adobe made its announcement about the latest innovations to its Adobe Campaign Email Solution. The innovations are designed to help brands match up to increased consumer expectations from emails, and offer brands a chance to lead with experience.
The innovations are mainly driven by its machine learning functionality powered by its Sensei AI platform. They include predicting the best images for emails, predicting churn and opt-outs (and ultimately taking timely steps to prevent it), flexible and visual analytics to make quicker insight-based decisions, the ability to craft multi-lingual emails simultaneously (via an integration with Adobe Experience manager) and finally, over 18 new out-of-the-box templates for better designed emails.
Adobe Campaign in Adobe Marketing Cloud, part of Adobe Experience Cloud, enables marketers to send hyper-personalized, engaging emails based on customer knowledge and interactions. Artificial intelligence and machine learning, through Adobe Sensei, power Adobe Campaign's predictive capabilities. "As brands continue to embrace email marketing as a pivotal component to build delightful, holistic experiences, many struggle with meeting customers' heightened demands," said Stephan Dietrich, vice president, Adobe Campaign. "Our new email innovations further cement our leadership in helping enterprises provide well-designed emails that enhance customer relationships, brand awareness and ultimately sales."
Adobe Campaign, part of Adobe Marketing Cloud, enables the orchestration and delivery of contextual email and cross-channel marketing campaigns to fuel meaningful customer experiences with scalability and ease.
Sneha comes with six years of experience in inside sales, where she was responsible for driving demand gen campaigns of technology products in the APAC and EMEA regions. Her zeal f Read more
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Quality Rating
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Posted on April 25th, 2011
Very Good DR. Followed through with pain management did not leave me to my own accord when trying to stop using pain medicine like most physicians do. Hope you are still in practice!!!
Dr. Hochreiter
Posted on September 14th, 2009
I'm so glad I found Dr. Hochreiter! He's a wonderful, honest doctor with enough experience to have 'been there done that' yet up-to-date on the latest in orthopedics. I've had two surgeries with him and I hope he's in practice for a long time to come.
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Radio Shack
Here's my updated Radio shack. New additions include: 1) An Icom IC-2200H 2m transceiver for local radio nets, 2) a 24-hour UTC clock, 3) more tidying. The Antenna Analyzer is on loan from W7MSO (Thanks!) to produce the detailed SWR graphs using gnumeric on Linux.
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Following the Eaves Wood event on Saturday 11th November the final league scores are available here. There was fierce competition from a record number of schools, but eventually we have the two winners. Christchurch C of E Primary School, Lancaster are the winners of the Primary League, with St Wilfrids C of E, Halton in second and Moorside Primary, Lancaster in a very creditable third.
In the Secondary League Lancaster Royal Grammar School were first (following their success earlier in the year in the Orienteering Challenge Trophy) with Lancaster Girls' Grammar second and Ripley St Thomas third.
Very many congratulations, not only to the winners but to all schools and everyone who took part.
For those who took part and want more orienteering see the fixtures tab of this website (note that the fun New Year Cracker on 1st January is also in Eaves Wood!) and the British Orienteering event diary.
Monday, 13 November 2017
Saturday, 11 November 2017
Eaves Wood results
Thank you all for coming to today's event at Eaves Wood. We certainly had wonderful weather for November. The results can be found here. This is the 3rd and final event of the Lancaster and District Schools Orienteering League. The school league tables will be published in the next couple of days – when the winners of the Primary and Secondary Trophies will be announced!
Any queries on the results to me, Martyn Roome on firstname.lastname@example.com
And a big thank you to the organisers of and helpers at all of the Autumn events
Friday, 10 November 2017
Street League scores
Scores for event 2 are now available here. You can also view gross scores and age adjusted scores so far.
Thursday, 9 November 2017
Plungington RouteGadget
Apologies for not posting RouteGadget for the Plungington street league event two weeks ago. It's live now here.
Night Street League event 2, Lancaster South
A pleasant evening weather-wise, a hilly challenge and a new venue, greeted what may well have been a record numbers of runners at the second event of the season. RouteGadget for the event is here, share your routes and see what others did. Results will follow soon.
Monday, 30 October 2017
OMM success for SROC pairs!
The Original Mountain Marathon was held over the weekend, based in Langdale. Strong winds and low visibility dominated Saturday's race but did not deter Zoe and Quentin Harding who finished first on the A course. Second were Iain Embrey and John Ockenden and these positions were held after Better conditions on Sunday. Congratulations to these four and to the other SROC members who completed their courses when many others retired. Results here. Photo thanks to the OMM website.
Street League season starts well
The first event in the SROC Night Street League was held on a new map of the Plungington area of Preston last Wednesday and was well attended with a few new faces along with the old hands. Results are on line here. The next event is in Lancaster, followed by Thornton-Cleveleys a fortnight later. Details on the fixtures list.
Monday, 9 October 2017
Lancaster & District Schools League scores
The scores have been updated after the Williamson Park event and can be read here. Christ Church have opened up a gap in the primary section, whilst Lancaster Royal Grammar School have overtaken Lancaster Girls' Grammar in the Secondary section.
The final event, where the trophies will be decided, is at Eaves Wood, Silverdale, on Saturday 11th November. Make sure YOUR school is well represented!
Questions about this event to email@example.com
The final event, where the trophies will be decided, is at Eaves Wood, Silverdale, on Saturday 11th November. Make sure YOUR school is well represented!
Questions about this event to email@example.com
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Not easy to find a high standard accomodation with perfect wellness in combination with the southern ambiance, food and a splendid home made wine.
We found it and we will definitily come back, easy acces with Ryanair or the high speed train, even for a weekend.
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text: Hi Tom, I would be interested in another PHC sprint, or maybe one based on another simpler, popular Plone product. I must spend some "quality time" with PHC, just to figure out all of what it can do. I did heed the warning to get PloneTestCase and ZopeTestCase from CVS. Here's a simple recipe (taken from SF.net), in case anyone's interested: cd yourPloneDir LOGIN="-d:pserver:anonymous at cvs.sourceforge.net:/cvsroot/collective" cvs $LOGIN login ## just hit Return, when prompted for a password... cvs -z3 $LOGIN co -P ZopeTestCase # (or/and?) PloneTestCase ## CMF Products in CVS can be "seen" at: ## http://cvs.sourceforge.net/viewcvs.py/collective/ Still working through the PTC tutorial(s), ----mark Tom Bryan writes: > Hi, all. In working on http://members.plone.org/documentation/tutorial/cvs, I > hit some issues with PloneHelpCenter (PHC). I've been talking with limi and > optilude on #plone about maybe doing some more focused bug fixing on PHC so > that they can put a newer version of PHC up on plone.org. > > Would anyone be interested in meeting somewhere locally for a PHC sprint? Not > sure when, but if you're interested in doing a bit more Plone development and > unit testing, it might be a nice chance to do so. I know that I would be > much more productive if I could pair program with someone so that onen of us > could dig through APIs while the other one wrote the code. > > If anyone is interested, then I'd be looking at doing it in the next week or > two. I'll be starting at a new job soon. > > ---Tom > > _______________________________________________ > triangle-zpug mailing list > triangle-zpug at starship.python.net > http://starship.python.net/mailman/listinfo/triangle-zpug


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23previous - next - BM Home - Full Page
2 Samuel 21
THERE is a painful interest in many portions of the Old Testament, where war and bloodshed enter so largely into the sacred history, and where the Divine Being Himself is not infrequently represented as seeking satisfaction in the death of His creatures. Yet these are the parts of Scripture that require our most careful attention. The appearance they present of cruelty or injustice, and of undue severity on the part of the Infinite, if left without satisfactory explanation, has a tendency to diminish our reverence both for the Scriptures and their Divine Author. But when we reflect that such difficulties not only admit of a satisfactory solution, but afford useful spiritual instruction, we have a double inducement for making them the subjects of reflection.
Under a religious dispensation in which the states of the Church were exhibited in their effects in outward nature, a famine that continued for three years, year after year, could not fail to excite in the mind of every pious Israelite a fear, if not a conviction, that some unknown and unacknowledged evil reigned amongst the people. Under such an impression David inquired of the Lord; and he received for answer, "It is for Saul, and for his bloody house, because he slew the Gibeonites." The tragic sequel, the death of seven of Saul's house, and the burial of their bones with those of Saul and Jonathan, are represented as having removed the cause of the famine; for "after that God was intreated for the land."
There are several reflections which this relation suggests.
In the first place, God did not make known by immediate revelation the consequences that must ensue if the crime of Saul were not followed by suitable atonement; but He allowed the famine to fall as a scourge upon the people, and to continue, till they themselves should search out the cause. Of this mode of dealing with His people there are many instances recorded in the Scriptures. And these are no doubt designed to instruct us in the nature of a part of the Divine economy of which we ourselves are the subjects.
The Lord has revealed His will and given us laws, for our instruction and direction in the life of righteousness. If we violate any of those laws, or do what we know to be contrary to the Divine will, the revealed Word assures us that we cannot be forgiven but by repentance and amendment. And if the evil is not removed, its consequences must of necessity fall upon us, that we may be led to self-examination before God, in order to trace the effect up to its cause, and seek His direction and aid for its removal. In many things also we can only be taught by experience. Not that there are any circumstances in which we are left without sufficient direction to walk in the right way. But such is the human will of fallen man, that it cannot be subdued without tasting of the bitter fruits of sinful indulgence. And as man is to be led in freedom, both to resist evil and to do good, he is left to act freely; and on this ground the Lord teaches him through his experience freely to forsake the path of sin, when he has neglected to obey the truth as revealed.
In the second place, the crime of Saul is not visited on him nor on Israel during his time, but on his descendants and on the people in the time of David. In the Israelitish Church, in which all things were representative, guilt is often punished on others than those by whom it is immediately committed. The iniquity of the fathers is visited upon the sons. In the Divine view Israel was considered to be one, and, spiritually, Israel represents one man. The men of Israel represented the principles of the mind of this one man, and the periods of the Israelitish history represented the stages of the regenerate life. The crimes that were punished on the descendants of those who committed them represented those evils that are not checked in their beginning or interrupted in their progress, but are allowed to run their course till they have reached a crisis, which ends either in death or restoration. An evil that exists in the will may not be seen or arrested there, but may branch out into the affections and thoughts, or even into the words and actions, before it be successfully opposed. And the affections and thoughts, in relation to the will and understanding, are as children in relation to parents; and are represented by them in the Scriptures. The derivation of evil in the will into the affections, and of falsity in the understanding into the thoughts, is spiritually signified by the declaration in the decalogue, that the Lord visits the iniquities of the fathers upon the children to the third and fourth generation of them that hate Him. Three and four do not mean simply a series, but one number has relation to the understanding and its falsity, the other to the will and its evil. And these principles, when rooted in the will and understanding of the mind, branch out into the affections and thoughts. It is in this more ulterior form that they are, in many cases, first discovered, and that they are brought to judgement. This would appear to be the reason that, in the present instance, the descendants of Saul were punished for his sin, and that there is no previous record of the sin itself as committed by that king. The famine was for Saul, because he slew the Gibeonites. But this is the first time that that crime is mentioned. Nothing is said in the history of Saul of his having destroyed any of that people. So, in our experience, there are evils that are only brought to our remembrance and consciousness as sins long after they have been committed; and evils may have had a deadly activity in the will that have only been truly seen and condemned when they have descended into the thoughts of the understanding.
The crime of Saul which was visited by famine upon the people and death on the seven men of his sons requires our attention. The singular history of the introduction of the Gibeonites into the congregation is well known and must be familiar to every reader of the Bible. When Joshua entered as a conqueror into the Promised Land, this section of the Hivites, and here called a remnant of the Amorites, "did work wilily, and went and made as if they had been ambassadors, and took old sacks upon their asses, and wine-bottles, old, and rent, and bound up; and old shoes and clouted upon their feet, and old garments upon them; and all their provision was dry and mouldy. And they went to Joshua to the camp of Gilgal, and said, We be come from a far country: now therefore make you a league with us." So "Joshua made peace with them, and made a league with them to let them live; and the princes of the congregation swore to them." When the fraud was discovered, although the oath could not be broken, Joshua said to them, "Now therefore you are cursed, and there shall none of you be freed from being bondmen, and hewers of wood and drawers of water for the house of my God." The oath with which the covenant was confirmed was then to be held inviolate. Saul was the first and the only one who broke that sacred engagement, although there is no record of when or how the engagement was broken. And an act which set at nought a solemn compact, and was visited by such serious consequences, must represent an evil of a very serious character.
Of the seven nations of Canaan devoted to utter destruction, two were partially received into connection with the Israelitish people—the Hivites by covenant, the Jebusites by sufferance. This partial exception was made in their case, because the Hivites represented idolatry in which there is something good, and the Jebusites idolatry in which there is something true. In relation to those who are being regenerated, whom these seven nations represented so far as regards all the corrupt principles which make up the life of the natural mind as it is hereditarily, the connection of the congregation of Israel with a remnant of two of these nations represented the preservation of every good natural affection and thought, or of every natural good and truth in the mind, and its conjunction with the spiritual good and truth acquired by actual regeneration. Everything is preserved and regenerated that is capable of being bent into conformity with any good end, and that can be made to render any real spiritual service, however lowly or limited. The external character of the good which the Hivites represented, and the external character of the service they were capable of rendering, was represented by their being made hewers of wood and drawers of water to the house of the Lord, this service indicating a cultivation of the knowledge of good and truth, not for their own sake, but as a matter of duty, as a labour, not of love but of service. Yet this service is useful and necessary, and when performed faithfully, is to be received as a use rendered to the Lord and His kingdom; and, like many of the lower uses of religion, forms a means by which the higher uses are preserved in their activity. To destroy these principles, therefore, would be to destroy the use which a beneficent Providence has appointed them to perform; but to destroy them, as Saul sought to do, after a solemn covenant had been made with them, is to seek to dissolve their conjunction with the principles of the spiritual mind, and to deprive both of the mutual use and stability which conjunction secures.
This was the sin which brought a famine for three years upon the land, denoting the privation of the means of supporting the spiritual life, when such a violation of faith and integrity is attempted, though not fully carried into effect.
The death of seven of the men of the sons of Saul represented the removal of the evils and falsities derived from that original and ruling principle in which the crime originated. Although this remedy was demanded by the Gibeonites, it appears to have been approved, and even required, by the Lord Himself. But this does not teach us that the Lord punishes the sins of the fathers upon the children in a spiritual manner; but only that order itself produces, and the Lord provides, the judgement of justice against evil, either in its beginning or in some of its derivations. Painful in a natural point of view as the present relation is to our feelings, it is no doubt intended to impress us with the conviction that the spiritual result of evil, of which it is the symbol, is still more harrowing to the spiritual affections. These natural sorrows have an end, and time itself exhausts them; but those which are spiritual, if not corrective, endure for ever.
Connected with this historical circumstance there is a touching incident recorded in the conduct of Rizpah, the concubine of Saul, and mother of two of the sons who were put to death." She spread sackcloth upon the rock, from the beginning of harvest till water dropped upon them out of heaven, and suffered neither the birds of the air to rest upon them by day, nor the beasts of the field by night. In this we may recognise the unwearied watchfulness and extreme tenderness of womanly affection, especially when that affection is exalted into maternal love. Infamy cannot destroy it, misfortune greatly exalts it; and when all others' hearts are cold or careless, there is one at least that remains warm and watchful by day and by night. In this beautiful instance of feminine and maternal love we see the symbol of inward spiritual affection in its desire and its care to preserve the principles of the Church from being destroyed by falsities and evils. For both Saul and his sons represented the principles of the Church, although in their states of opposition to the Lord's cause they represented those principles perverted. Such is the representation of the men of the sons of Saul in the present instance. The principles of the Church are perverted when our own evil life, or our own evil ends, enter into them and rule them. When, as in the case of Saul's sons, the evil life is destroyed or removed, the principles themselves are holy, and become filled with a new and higher life. As holy things, they are to be preserved by the watchfulness of the spiritual affections from the devouring tendency of the natural lusts and passions, which, like birds and beasts of prey, are ever ready to consume whatever is good and true in the mind. The watching of Rizpah is said to have been continued from harvest till water dropped upon them out of heaven. Harvest in the Word signifies the completion of a state, the time of consummation and decision, when there is an end and a separation; the harvest being gathered in, the wheat is stored up in the garner, the tares are burned in the fire. But when, after the labours and the drought of harvest, the rain drops out of heaven, when truth descends from the heaven of the inner man, and falls, like a refreshing shower or the gentle dew, upon the outer man, a new state begins, and the days of mourning are ended—the sackcloth spread upon the rock ceases to be the couch of the holy watcher. The pious care of Rizpah is told to David, and David completes the object of her care and solicitude by gathering the bones of the seven men, with those of Saul and Jonathan, and burying them in the sepulchre of Kish. After that God is intreated for the land. In Scripture burial signifies resurrection; for while men bury the body, angels welcome the spirit into the eternal world. In the view of angels death and burial have nothing sad or destructive in them. They see only the immortal soul entering into a new and higher life; and in the spiritual, which is the angelic, sense of the Divine Word, life and immortality take the place that death and burial occupy in the letter. The burial of the bones of Saul and his sons by David represented the rising into higher and purer life of the Divine truths of the Church, after being purified from the perversion to which they had been subjected. This is effected by the Lord, of whom David was an eminent type. They were buried in the land of Benjamin, in the sepulchre of Kish, the father of Saul; for the land of Benjamin is the intellectual mind, and the sepulchre of Saul's father, Kish, is the life of love or goodness.
When we view the subject in the light of the spiritual sense we can see our way to a satisfactory solution of the difficulties presented in the simple historical sense, and at the same time draw from it instruction for our guidance in the life of righteousness.
When the evils that obstruct the operation of the Divine mercy and truth are removed from our souls, the sunshine of heaven falls with its blessed influence upon them, and serenity and joy are restored. Our souls become barren when they are turned away from the Lord; but when we turn to Him with the whole heart, and enter into new life, God is intreated for us—He is favourable; and in His favour is life. Of course we do not mean that any change takes place in the Divine mind. Such is presented in the appearances of the letter. The spiritual sense teaches us that the change is in man. The Divine Being is ever favourable, ever kind, but His favour and kindness are turned away by the sins of His creatures, and How in abundance into the human heart when men are willing and obedient.
When we find ourselves without the inward consolation and outward fruitfulness of the heavenly life, we should examine ourselves to discover the cause. And having made the discovery, we should put away the evil of our doings from before the eyes of the Lord, and the light of the Divine countenance will shed joy over our inward life and render our outward life fruitful in all good works.23 previous - next - BM Home - Full Page


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