Document r6k0m4eoLL012kB4yOQzBDYEr

.< ANALYSIS OF DR. ROBERT KEHOE'S MEDICAL SUMMARY OF MRS. CASE HISTORY N 5251 PREFACE In o rd e r to a ssim ila te the following reb u ttal m a te ria l to D r. K ehoe's rep o rt, the re a d e r m ust re fe r to the Kehoe re p o rt p a ra g ra p h by p a ra g ra p h , a s the a n a ly sis of D r. K ehoe's r e m a r k s a re so arran g ed in th is discussion. The re a d e r is fu rth er encouraged to re fe r to the sources / noted as the b asis for the discussion w here technical m atters a re n e ce ssa rily dissected and exam ined. Some graphic c h arts a re included a t the end of this a rtic le fu rth e r to elucidate technical discussion. 1 D efinitions of T erm s used in P arag rap h I 1. "chronic c h o lecy sto lith iasis" - re fe rs to chronic gallbladder inflam m ation with gallstone form ation (treated by gallbladder rem oval) \ "endom etrial disfunction with an hem orrhagic condition of the endrom etrium " - re fe rs to abnorm al vaginal bleeding due to horm onal disturbances (quite common in women). "influenza with h y ste ric al m anifestions" - re fe rs to an episode of v iru s flu (what D r. Kehoe re fe rs to as "h y sterical m anifestions" is unknown to me) "acute sta te s of anxiety" - re fe rs to episodic s tre s s reaction to re a l organic d ise ase p ro c e sse s, quite common to any re a lly sick individual. "m igraine" - re fe rs to a type of sev ere headache, the exact cause of which is still quite obscure to m edical science. "acute u rin a ry retention" - re fe rs to episodes of difficulty in passing urine, secondary to bladder infections (quite common in women) "anxiety n e u ro sis with conversion" - re fe rs to s tr e s s re a c tio n s to r e a l org an ic d ise a se sta te s (again noted to be quite c o m m o n ly . seen in sick individuals) " g a s tritis and functional p ylorospasm " - re fe rs to episodes of inflam m atory reaction in the stom ach associated with apasm of the m uscular outlet valve of the stom ach, the pylorus. "probable pyelonephritis" - re fe rs to infection of the kidneys (also common in women) "subdeltoid b u rsitis " - re fe rs to an inflam m atory condition of the b u rsa (a stru c tu re which cushions the action of tendons and m uscles a cro ss joints) located at the shoulder under the deltoid m uscle - a v ery comm on condition. "m yalgia and a rth ra lg ia " - re fe rs to episodes of pain in m uscles and joints (a condition com m on to m any usual and unusual illn esses) . 1S < 2. 12. "cy stic o v a rie s" - a condition of the fem ale ovary in which norm al egg follicles fail to ripen, the egg degenerating, and the follicles enlarging, filling with fluid- again, a common fem ale disorder. 13. "m ultiple pelvic and abdom inal adhesions" - r e fe rs to s c a r tissu e form ation occuring in n early all persons who have undergone su rg ery , in the abdom inal and pelvic regions u n d er lying the operative site s. - 14. " re c u rre n t lu m b o sac ral a b n o rm a litie s of the spinal colum n" r e f e r s to w ell su b stan tiated organic d ise a se of the low back in this c ase ruptured v e rte b ra l disc and its sequelae, req u irin g surgery. > 15. "sciatic n e u ritis" - re fe rs to an inflam m atory condition of the sciatic n erv e {located from low back, through buttock, and into into thigh and leg, to foot). ^ 16. "g a stric u lc e r" - r e f e r s to u lceratio n (via chronic inflam m ation) of the m ucus m em brane of the stom ach. In this section, D r. Kehoe rev iew s the p resenting signs and sy m p to m s of M rs .'l^ p m ^ ^ l 9 6 d O c to b er a d m iss io n to Good Sam aritan H ospital, during which the diagnosis of Plum bism (lead poisoning) was m ade. She did indeed p resen t with evidence of bowel inflam m ation, and my initial im pression was that she may be suffering from d iv erticu litis (sm all packets of bowel m ucus m em brane which h ern iate through sm all blood v essel openings into the bowel wall, which m ay becom e inflam m ed-- such as in appendicitis). Inflam m ation, r e - 1t g ard less of its cause, m ay indeed c reate fever, as infection caused by b acteria, v iru ses, fungi, o r unicellular anim al p a ra sites. N ausea is a common feature of any gut inflam m atory p ro cess. \ 3. X -ray exam ination of the bowel failed to dem onstrate d iverticulitis, or other bowel disease responsible for the p a tien t's com plaints and findings. C onsulation with D r. Sylvan W einberg ( a reputable internal m edicine specialist) was obtained. He also was unable to explain the p a tien t's problem . T herefore, a search for exotic causative agents was m ade. It is known that poisons m ay cause such a sympton complex, and tests w ere th e re fo re m ade for a rsen ic , zinc, antim ony, and lead; urine being the m ost available source ( h air and nail clippings also w ere subm itted blood being om itted due to its tran sie n t carry in g capacity fo r such toxic substances). All studies w ere negative except fo r the finding of a g rossly abnorm al lead level found in the u rin e. The diagnosis of lead poisoning was thereby established; the patient's sym ptom s being due to colic (spasm ) in the g a stro -in testin a l tra c t secondary to the toxic effects of lead. Comment D r. K ehoe's re m a rk s in the third paragraph seem to im ply that the diagnosis was arrived at by "spontaneous generation", as if by "divine revelation", ra th e r than by good investigative, logically deduced, procedure. 4. A search for red blood cell basophillic stippling was m ade ( a condition of precipitation of W right's stain blue dye in the red blood cells as seen under the m icroscope on a slide prepared from peripheral blood). A search for elevated content of urin ary porphyrins also was m ade ( a chem ical p resen t in urine as a re su lt of abnorm al breakdown of the red blood cells and its oxygen bearing m olecule, hem oglobin). Both te sts w ere negative. T hese, when positive, a re considered ancillary evidence of the presence of a toxic substance ( heavy m etal - lead, etc. ). It should be noted that stippling and porphyria a re m ostly evident in cases of acute lead poisoning (large doses in a short period of tim e), in sm all children who a re exposed to paint lead sources (crib r a ils , w all paint, e tc .). In children, w hose m etabolic p ro c e sse s a re accelerated (building all tissu e s rapidly, including bone, bone m arrow , and red blood cells) it is consistent that since lead com plexes with, and deposits in bone, that the m etabolic p ro c e sse s of the red blood cell, a product of the m arrow , should th ere fo re becom e abnorm al, and that stippling and porphyria would be p resen t. C hildren also (because of accelerated bone growth) will show a "lead-line at grow th-plate m etaphyses of long bones by x -ray , when they becom e poisoned by lead. A "lead -lin e" can be seen in th eir gum s; fo r the sam e reason, with the growth of th eir teeth, when poisoned with lead. H ow ever, in an adult, with no grow th proceeding, but only re p a ir 5. and d eg en erativ e p ro c e sse s of m etab o lism , and in a case of ch ro n ic ex p o su re to lead ( o v e r a long period of tim e ); it would not be unusual to not find basophillic stippling of the red blood cells, nor a lack of increased porphyrins in the u rine. D r. K ehoe's description of a patient afflicted by lead toxicity (in "uncom plicated plum bism ") is vivid and perhaps accu rate. M rs. ^ I f l U ^ d i d in deed suffer g astro -in testin al colic as d escrib ed , on m any occasions (resu ltan t in u lc e r form ation, s tre s s reactio n s, abnorm al gut m etabolism , with reactiv eh y p o g ly cem ia, seco n d ary p a n c re a titis, e tc .). She did in deed g rim ace, and grind h e r teeth . She held h e r left side and abdomen m any tim es - perhaps this was an attem pt to reliev e C h er d istre ss as D r. Kehoe d escrib es. And, as D r. Kehoe has so aptly noted, she did suffer m any secondary infections and in flam m ations, which com plicating h e r lead problem , did in deed cause h e r fever. F ev er was a facto r, which ra th e r than casting doubt on the diagnosis, substantiated the existence of inflam m atory reaction and com plication of h e r lead problem . ,, Comment I th erefo re re je c t D r. K ehoe's conclusion that the absence of stippling, absence of porphyrins, and presence of fever, m itigate finally against the diagnosis of plum bism . I also object to this line 6. of reasoning and conclusion (for the above stated explanation), m ade by a physician not engaged in clinical p ractice, who has never exam ined by h istory or physical the actual patient, and who m akes such ra sh statem ents by v irtu e of his perusal of reco rd s alone. By being this p atient's physician, actively engaged in h e r health problem s fo r the past num ber of y e a rs, I subm it I am th erefo re infinitely m ore qualified to judge h e r condition and m ake the appropriate diagnosis. . D r. Kehoe d ecries the use of urine as a source of m aterial for the exam ination and detection of lead, and obviously p refers blood as a source. This is directly opposed (see Goodman & Gilman, The P h a rm a c o lo g ic a l B a sis of T h e ra p e u tic s, 1956 E dition, P ages 1007-8) in m o d em in v estig ativ e th eo ry . In acute lead poisoning, blood in deed would be a rea d ily available so u rce, with its high tra n sie n t lev el secondary to an acute ingestion of lead in high concentration. It is known that in subacute, and in chronic exposures to sm all doses of lead, blood levels a re very tran sien t and low in concentration. Upon leaving the blood, lead en ters the bone and com plexes with its calcium la ttic e stru ctu re, with lead reaching an equilibrium chem ical balance at low concentration with blood lev els. Lead m ay then leave the bone under the influence of * EDTA lead com plexing therapy, into the blood, and can readily be detected in the u rin e upon kidney filtratio n of the blood. W henever a lead so u rce is discontinued, blood le v e ls of lead drop ( as do u rin e lev els). Bone lev els ris e , and w ill only decom plex when treatm ents a re instituted. T herefore urine is a b e tte r so u rce fo r lead determ ination, and is especially so in a case of chronic lead poisoning - a s in M rs. case. It is also tru e as D r. Kehoe points out, that lead is ubiquitous, and that healthy urban dw ellers m ay have lead detected in the u rin e (m ost often fro m inhaling the products of com bustion of leaded gasoline in the engines of autom obiles - this fact I understand D r. K ehoe's entire re se a rc h experience h as been dedicated to d isc re d it, as it h a s been s ponsored by the petroleum in d u strie s. However,, when lead lev els reach a certain high point of concentration in the u rin e, a point which has been established by m edical re se a rc h , it is known to be toxic to the individual te ste d , and is capable of producing sym ptom s. M rs. urine lead lev els w ere twice as high as this known toxic level (see attached table of laboratory resu lts). D r. K ehoe's exam ple of two m en w orking side by side takes into account only exposure by inhalation (or at le a st a source common to both, at the sam e concentration to both), not as in M rs. ^ ^ m ^ a s e by h e r usual inhalation exposure ( as she is a city dw eller) plus an ingestion exposure source. She has been, a s D r. Kehoe has pointed out, not a healthy working m ale, 8. disease states. As to the "deplorable" conditions under which M rs. flaboratory studies w ere ordered, collected, and exam ined, I invite him to inspect Good Sam aritan H ospital's Special C hem istry Clinical L aboratory, and discuss any phase in question with the hospital pathalogists responsible for its operation, the PhD, who actu ally conducts the testing, o r the R N 's of the N ursing S ervice who follow m y o rd e rs and who a re responsible for the collection of all specim ens. A copy of the exact technic used in the L aboratory with refe ren c e m aterial is attached to this re p o rt. Comment A nalysis of D r. R obert K ehoe's "consideration of the alleged source of lead, allegedly absorbed by the patient, M rs. w m m Comment A fter the diagnosis of lead poisoning w as established in M rs. case, a search was instituted for a possible source of lead in h e r im m ediate environm ent. Inasm uch as M r. ; R o b e r t ^ m ^ ^ h e r husband,was also intim ately exposed potentially to the sam e environm ent, a tw en ty -fo u r h our u rin e w as collected on him and exam ined fo r lead . No toxic lead lev el w as detected, f t - 0000095 effectively ruled out. 9. It is known that c ertain ceram ic kitchenw are m ay contain a glaze which m ay incorporate lead. The possessed such a possible source, a teapot, purchased at M cC rory's Store, % which w as im ported from Japan, its site of m anufacture being obscure. M rs. alone brew ed and drank tea from this ceram ic pot. The pot w as analyzed, and did in deed contain high quantities of lead. M oreover, it w as ascertain ed , that between hospitalizations (during which she w as tre a te d , unexposed to m o re lead, and su b se quently im proved), it w as h e r habit to consum e tea, which is com m only given to recu p eratin g patients especially with g a stro in te stin a l d iso rd e rs , fro m th is pot. In sh o rt o rd e r, she would again experience episodes of severe gastrointestinal colic and req u ire re-hospitalization (for "pylorspasm , u lcer, diverticulitis, and the "like", without benefit of knowledge of the truth of the source of h e r com plaints). It is all too c le ar, at this point that lead w as in deed the culprit, and that the innocent teapot, the veritable source. D r. Kehoe quite obviously questions the re su lts of the testing of the ceram ic pot in question, I leave the disputation of the analytical re su lts and m ethods of testing to the experts. As fa r a s I am concerned, tannic acid (tea solution) is of sufficient potency . (esp ecially if brew ed strongly) to c re a te a w eak solution of lead (extracted from the lead-based ceram ic glaze), which when ingested reg u larly , over a period of tim e, is quite adequately the source of toxic 10. poisoning in the case of M rs. I can appreciate the in adequate resu lt obtained by the reknowned K ettering L aboratory, of actual lead extraction from the teapot in question, when one realizes that the sam e teapot had been subjected to strong acidification (not a weak solution of tea-tan n ic acid) by two previous lab o rato ry exam inations (WPAFB & B ow ser-M orner). R espectfully subm itted See Attached Tables APPENDIX D r. K ehoe's R eport Table of U rinary Lead D eterm inations 4 L ead - In Blood o r U rine Table of P orphyrin M etabolism as re la te s to Lead T able of A bnorm ally Produced Red Blood Cell M etabolism TABLE OF URINARY LEAD DETERMINATIONS performed by The Special Chemistry Laboratory (headed by Dr. Haddox a Ph.D. in Biological Chemistry) of Good Samaritan Hospital Date Test Ordered Date Done 24 h r . u r i n e c o l l e c t i o n ) Result m g m /l Control m g m /l IO /24/ 69 I O / 3 1/ 6 9 11/ 6/69 a s OP nn tl t t tt tt ir ft as OP IO /29/69 11/ 3/69 II/IO / 69 12/ 5/69 I / 20/ 7O 2/ 5/ 7 O 5/ 6 / 7 0 5/ 2 1/ 7 O 8/ 2 5/ 70 O .I 7O I . I 30 0.044 . 0.021 O .O 68 0.120 0.042 0.040 0.002 * O .O I5 0.020 0.018 0.020 O .O 3 O 0.020 0.022 O .O I5 0.018 [husband) 10/ 30/ 69 0 .0 0 1 O.OI5 Normal lead level (urine) Toxic level (according to Kehoe & Associates in 1947 ) 0.01 to O.O3O greater than 0 .0 70 mgm/l LEAD - In B lo o d o r U r in e I. DIGESTION 1. A 100 ml. aliqnot of 24 hr. urine specimen or 10 ml. of blood placed in round bottom flask with several glass beads. 2. Add 150 ml. HN03 + 6 ml. H2SO4 . Heat until volume is approximately 50 ml. (Boil gently at first to avoid foaming over). 3. Remove flame and add 50 ml. more of HMT3 and (carefully and slowly) add 5.0 ml. of cone, perchloric acid. {72%) 4. Heat again until solution clears and white SO3 fumes are copiously evolving. Usually occurs when volume is down below 4.0 ml. Remove heat. (If not a clear colorless syrupy liquid, add a few more ml. of HN03 and heat again until SO3 fumes copious. Should be repeated until get the clear liquid). ' II. COPPER and IRON REMOVAL 5. Acid 15 ml. of AMI40NIUM CITRATE and 1.0 ml. of HYDROXYLAMINE HCl. Cool and add NH^OH until gust alkaline to phenol red. Then add 5.0 ml. of KCN solution. (If precipitation occurs, add gust enough citrate solution to dissolve it). III. DITHIZONE EXTRACTION 6 . Transfer to separatory funnel (50 to 125 ml). , 7. Add 5 m3. of dithizonc extraction solution. Shake and drain off into another Separatory funnel (125 to 250 m l ). (The dithizone will turn red if Pb. present). 8 . Continue adding 5 ml. portions of the dithizone extraction solution until all the lead is removed and the solution remains green. Each portion is in turn combined with the previous portion. 9. Add 50 ml. of the Buffer solution (pH 3.4) to get the lead in the aqueous phase. Shake thoroughly. After settling, discard the chloro form phase(wnich should be a light green). IV. COLORIMETERIC DETERMINATION , 10. Add 10 ml. pure chloroform to separatory funnel to remove any residual dithizone. Discard this chloroform wash. ' 11. To the buffer solution in the separatory funnel, add 10.0 ml. of the proper Dithizone standard solution (estimated from steps 7 & 8 above) and 10 ml. of ammonia-cyanide solutionjadd the Solution well shaken. 12. After separation of layers, flush the funnel stem with the first few drops. The remainder is run directly into the colorimeter tube for reading at 510 mm. (Read against reagent blank (see #l3)jif available on a pure lead free Dithizone solution. . -2 LEAD - In 31ood, o r U r in e ( c o n t in u e d ) 13. The results are compared with the standard curve to obtain the amount of lead in the sample taken. (Appropriate calculation follow 'to adjust to blood % on urine/ 24 hr.) 14. A reagent blank should be run at same time, beginning with step #1 using 100 or 10 ml. of HOH in place of urine or blood resp. REAGENTS: (1) . AMMONIUM CITRATE solution - 400 gm. citric acid dissolved in HQH. Sufficient NH4OH added to make the solution alkaline to phenol red. Dilute to(l)liter with HOH. (2). HYDROXYLAMINE HYDEOCHIjOEIDE - 20.0 gra. + HOH to 100 ml. (3). * POTASSIUM CYANIDE (KCN} - 10.0 gm. + HOH to 100 ml. . (4) . .DITHIZONB EXTRACTION solution - 10 mg. DIPHENYL THIOCARBAZONE + 400 ml. CHLOROFORM. (Not important as to exact weight or Volume) (Solution should be aged several days before use) (5) . DITHIZONB STANDARD solution - Solutions kept in dark bottles out of light in refrigerator. Main standard - 20 mg. dithizone + chloroform to 1,000 ml. The Main Standard Used With 0 - 100 pg Range Dilute ^ for 0-50 pg range (i.e. to 10 mg./L) Dilute \ for 0-10 pg range (i.e. to 5 mg./L) (Age before use for several days) (6 ) . AMMONIA-CYANIDE solution - Dissolve 20 gm. of KCN in KOH. Add 150 ml. NH4OH. Dilute to(l) liter with HOH. (7) . BUFFER SOLUTION (pH 3.4) - To 500 ml. of double distilled water add 9.1 ml. of nitric acid and a few drops of bromo-phenol blue (or appropriate indicator); bring the pH to 3.4 with NH4O H . Add 50 ml. of Clark-Lubs buffer double strength, then dilute the solution to 1.0 liter. (Clark-Lubs buffer double strength: 50 ml. of 0.2 M potassium acid phthalate and 9.95 ml. of 0.2M HC1 + HOH to 100 ml.) .. .t ' . (8 ) . STANDARD LEAD NITRATE solution: 0.160 gms. dried lead nitrate diluted to 100 ml. with 1% HNO3 (equivalent to 1 ml. of lead). For use dilute in 1% HN03 to give 1 jig aj^d 10 pg per ml. 1 -3 LEAD -'in Blood o r U r in e ( c o n t in u e d ) (9)* STANDARD CALIBRATION CURVE; To a measured quantity of lead nitrate solution add 50 ml. of pH 3.4 buffer solution and follow procedure as outlined in procedure steps #10 thru. #13. (Suggest values of 1^, 2, 5, 10, 20, 100 tig Pb.) S'! ."jDk.ti'Ocr:,/v'.i'^I-**u ' C. C . y / / s t^ y 0 'X / JL^ L . a - 7 6 h -- < y x./ I / TABLE OF PORPHYRIN METABOLISM as relates to Lead. (Heavy Metal Intoxication) Porphyrin Tetrapyrrole Ring + Fe i Heme Molecule + Protein 4 Hemoglobin Molecule (incorporated into Red Blood Cell in Bone Marrow) I 120 day life cycle Splenic Degradation I Disrupted Tetrapyrrole Ring i Renal (Kidney) Excretion of porphyrin material ^ ' (May appear in urine of child or individual acutely poisoned with lead or other heavy metal) Not necessarily seen in urine of chronically poisoned patient TABLE OF ABNORMALLY PRODUCED RED BLOOD CELL METABOLISM Immature Red Cell: Cell protoplasm Nucleus with RNA Mitochondria with RNA-DNA complex Lead I Basophillic stippling noted as a result of lead precipitation of mitochondria - seen in peripheral blood 50 cells/lOO,000 examined of child or individual acutelypoisoned by lead or other heavy metal Breakdown as noted on Table of Porphyrin Metabolism as relates to Lead v Porphyrins in urine 7 Not necessarily seen in blood of chronically poisoned patient.