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April i HAWAII

MEDICAL

1999

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Volume

58,

No.

4

ISSN:

0017-8594

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•ø -, -J _,f- the virus. GM-CSF has been used to rescue patients with leukopenia effect on patients with chronic hepatitis C infection. Future studies on high dose interferon therapy but its efficacy as monotherapy for with higher dosage and longer duration of therapy or in combination 4 C has not been tested. In this study with interferon therapy are needed to prove its clinical efficacy as an the treatment of chronic hepatitis we administered rhGM-CSF to ten patients who have failed previ alternative and br adjuvant therapy for patients with chronic hepa ous interferon alpha 2-b treatment to study its anti - HCV effect and titis C. GM-CSF could also play a role in the treatment of those to assess side effects. The dosage given is low at 125 mcg/m2 patients with chronic hepatitis C who have significant leukopenia subcutaneously. The therapy was well tolerated with no significant and were excluded from interferon therapy. side effects. No dose reduction was needed and no patient withdrew from the study. The leukocytosis occurred as expected and eosino Acknowledgment:TheauthorswouldliketothankDr.RodneyWilliamsforhisidea Mr.Peter Hsinand Ms.Sharon Laifortheirtechnical philia was observed in two patients. Local injection site irritation and helpfulcriticism,to assistance. was common but generally manageable. Other side effects such as flu-like symptoms were much milder compared to that of the References: interferon therapy these patients had experienced previously, even 1. LieschkeGJ, BurgessAW.Granulocytecolony-stimulatingfactorand granulocyte-macrophage colony-stimulatingfactor(partI).NEngiJ Med1992;327:28-35, during the daily rhGM-CSF administration in the first two weeks of 2. MartinJ, Bosch0, Moraleds6, at al. PilotStudyofRecombinantHumanGranulocyte-macrophage the trial. Colony-stimulatingFactorintheTreatmentofChronicHepafitisB.Hepatology1993;18:775-80. 3. MartinJ, GuirogaJA, BaltolomeJ, at al. AntiviralEffectof RecombinantHumanGranulocyte The reduction in the viral RNA during the treatment was signifi niacrophageColony.stimulatingFactorinPBMCsofPatientswithChronicHepatitisB.Hepatology cant in the majority of the patients especially during the daily dosing 1993;18(Partll):118A 4. MartinJ,QuirogaJA,Bosch0, etal.ChangesinCytokineProductionDuhngTherapywithGranulocyte period. ALT was also noted to have improved in eight of the ten macrophageColony-stimulatingFactorinPatientswithChronicHepatitisB.Hepafology1994:20:1156- patients with normalization in three patients. These effects may be 61 5. CarrenoV, QuirogaJA. BiologicalResponseModifiersin ChronicHepatitisC. J. Hepatol.1995; due to cytokine production by the GM-CSF effect. GM-CSF has 22(Suppl.l(:122-26 KillsHerpesVirus-infectedbutnotNormal beenshowntoincreasetheliberationofTNF-alpha(TumorNecrosing 6. KoffWC,FansAV.HumanTumorNecrosisFactor-Alpha Cells.LymphokinesRes,1988;5:215-21 Factor Alpha), Interleukin-2 which themselves have potent anti- 7. TugH,VogelW,TratkiawiczJA,at al. PilotStudyofNaturalHumanlnterleukin-2inPatientswith viral ChronicHepatitisB. lmmsnomodulatoryandAntiviralEffects.J. Hepatol1993;19:259-67 activity. 8. HladikF,TratkiewiczJA,TilgH.at al.BiologicActivityofLowDoselL-2TreatmentinVivo.Molecular In summary,678 123the administration of rhGM-CSF in the doses used is AssessmentofCytokineNetworkInteraction.J. Immunol1994;153:1449-54 safe and’ well tolerated.’ The treatment seems to exert an anti-viral

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Teds Almanac “Circumcision,” the other replied. good for at least 10 years.” (From Hakobu Kuma gal’s desk) “Ihad one of those the day after I was born,” the She promptly replied, “Oh, I’ll be here for it. It is hard to believe that a man is telling the first man commented. “Afterward, I couldn’twalk But will you?” truth when you know that you would lie if you for a year.” were in his place. Conversation Stopper... I used to be indecisive, but now I’m not sure. Gravely ill, a man went to the doctor with his R. Bartlett MD Susex, N.B. is I have an open mind, it’sjust closed for repair. wife. After the exam, the physician motioned for An important part of the art of medicine The world is full of willing people. Some will the wife to meet him in the hallway... putting the nervous or embarrassed patient at ing to work and some willing to let them. “Your husband is very sick,” the doctor said. ease. Such was the case one beautiful April day One golfer to another: “First it was my mar “But there are three things you can do to ensure when a 20 year old woman was presenting for her riage, but now, the magic has gone from my nine his survival. First, fix him three healthful, deli first ever complete physical. iron, too.” cious meals a day. Next, give him a stress free While examining her breast, I made the inno Harvey’s Law: “you can’t fall off the floor.” environment and don’tcomplain about anything. cent comment, “Nice Spring.” Never underestimate the power of human stu Finally, make passionate love to him every’thy.” Her quick and some what short retort was, pidity. On the way home, the husband asked, “What “Yes, it’s because I’m still young.” did the doctor say?” A few seconds later, she suddenly realized my Life in These Parts... “I’m sorry,” she said, “but you’re not going to comment was about the season, not her tissue Insta Trak System (at SFH) make it.” turgor. The first computer image guided sinus surgery The rest of the examination was conducted with in Hawaii was performed on Nov. 13 by ENT Medical Tid Bits... minimal conversation with no further effort to man Roland Tam. Roland says, “The benefit I Efforts to Avoid C.Section Poses distract her from the indignities of her situation. found is that I knew my patient a lot better. Dangers... Before, we used a CT scan which gave us a A NEJM article by four physicians at Harvard Conference Notes... “Insulin Resistance” VP Robert Henry, UC San sampling of the sinus cavities. . It was like read teaching hospitals say that pressure from HMO’s ing every fifth page of a novel.. .This new and policy makers is leading physicians to en Diego, Friday, 8:00am, Queens Kam Aud Feb. 5, technology allows us to see the whole picture, courage vaginal delivery even when the risks are 1999. forward, backward, up, down, and sideways.” higher than with C section. The OB men are Ophthalmologist Jorge Camara performed sur concerned about an increase in uterine ruptures as A. Introduction: gery on a patient with proptosis. Jorge was equally well as injuries to babies caused by vacumn a. Pathogenesis Type II: ecstatic: “the endoscope allows the surgeon to devices and forceps. view the details through a small hole.. while the t hepatic glucose — t glucose Insta Trak system is like entering a home...It Re Birth Control Pill (liver) allows the surgeon to see where he is going in The latest issue of the British Medical Journal relation to theother adjacentrooms ofthe house.. reports that 46,000 British women tracked 25 insulin Peripheral insulin years showed no increased incidence of death 4 (pancreas) resistance(muscle) Euthanasia Opposed from cancer, strokes and other side effects. Thirteen organizations of physicians, nurses, More than 300 million women world wide have the disabled, hospitals and the religious right used the pill and an estimated 100 million are banded as the “Hawaii’s Partnership for Appro currently taking it. b. Progression Type II priate and Compassionate Care,” to fight the Bruce Stadel, medical officer of the US Food & Acquired proposal to legalize doctor-assisted death. The Drug Administration agrees that the latest study Genetics —+ Insulin Resistance 4— Obesity coalition included the Hawaii Medical Associa gives a “strong, resounding note that there is no 4 (Sedentary tion, Hawaii Family Forum, Hawaii Right to long term impact even with the highest dose Hyperinsulinemia life style) Life, Hawaii Christian Coalition, the American pills.” (The new generation of low dose pills is Age Center for Law & Justice of Hawaii, Hospice even safer) ‘I, Hawaii. Hawaii Catholic Conference, the Compensated Insulin Resistance Healthcare Association of Hawaii (representing Magnet Therapy Normal glucose tolerance hospitals and nursing homes) and the Hawaii Neurologist Michael Weintraub of New York Cancer Pain Initiative. Medical College reports in the Journal of Pain Management Jan issue that magnets may relieve Impaired Glucose Tolerance Physician Moves... chronic foot pain in diabetics and other ailments. Thomas Jimanez, chief of surgery, Rib Medi Twenty million diabetics are subject to painful, ‘Jr cal Center announced his recertification in general burning, numbness and tingling of their feet and Genetics —9 Beta Cell Failure +— Acquired surgery by the American Board of Surgery. hands... OB Gyn man Ronald Volt closed his private Paul Rosch, president of the American Institute 4. practice in Hilo on Jan 15. of stress who has written about the history’ of 4.hepatic Type II Glucotoxicity Hoon Park announced evening hours Mon-Fri magnet therapy says..”We don’tknow the mecha glucose output tGGA levels 8am-8pm at 868 Ululani St, Hilo, HI. nism by which it works.. It is all trial and error.” other The Hilo Family Practice Center closed as of Dec 31 (Family physicians Lynda Dolan, Laurie Potpourri II... Hopman and Jan Martell relocated their practice A Challenge? Insulin Resistance Syndrome at 409 Kilauea Ave. John Robinson MD Vancouver (Cardiovascular Dysmetabolic Syndrome) When the pneumonia vaccine arrived last Fall, Potpourri I... Iwent to visit one ofmy shut in .but very mentally Genetics Insulin Resistance 4 Environ- 90 old ladies... Two men were sitting in a doctor’s office. alert year Influence I mental “What are you here for’?”one asked. As I was giving her the shot, I said. “This is 4. Influence Hyperinsulinemia

HAWAIIMEDICALJOURNAL, VOL 58, APRIL 1999 102 c. Insulin Resistance Syndrome sensitizer; in Sulfonylurea failures, add of gastric contents... 1. Clinical Manifestations: Metformin to glyburide or Metformin with insu b. NERD: Non erosive reflux disease. a). Central obesity b). Glucose intol lin Rx; avoid when serum creatinine elevated erance c). HTN d). Atheroscleosis (Metformin is cleared by kidney) Prevalence of Heart Burn in US: e). Polycystic Ovary Syndrome * Thiazolidinedione: pure insulin sensitizers Controls Monthly 15% Patients 20% 1).Ciglitazone 2). Praglitazone 3).Priglitazone Weekly 14% 12% Insulin resistance in IGT and DM: Glucose 4). Troglitazone (4yrs) Daily 7% 13% disposal rates at identical glucose levels: * Troglitazone (Activities PPARy nuclear recep Normal > IGT> DM tor in skeletal muscle) GERD Spectrum: Time course of weeks and months; never Typical Insulin resistance: Pancreatic B Cells stop sulfonylureas when starting (Heart Burnl Regurgitation) Troglitazone (or any sensitizer); erosive esophagitis Troglitazone may reduce insulin dose in insulin E esophagitis* Normal Cells Abnormal Cells treated Type 2; Troglitazone reduces triglycer (Hyperinsulinemia) (Hyperglycemia) ides;raises HDL and LDL. Atypical Treatment schedule for Troglitazone: Start Angina like pain 200mg od for 2 to 4 weeks; then increase q Asthmalcough 2. Prevalence Insulin Resistance in Meta 2 to 4 weeks to maximum 600mg; check Laryngitis bolic Disorders: transaminase **Insulin sensitizers are Troglitazone and Complications a). ‘tcholesterol b). IBP c). turates Metformin... Ulceration d). IGT e). NIDDM Stricture Metaplasia* * f). tTriglycerides g). IHDL TRZ MET TRZ+MET (Barrett’s) h). tIGT/NIDDM + Dyslipedemia FBS -2 -20 -35 HBA1c 4—4 4—4 -1.2 *Requires abnormal pH-metry + turates: 95% MEAN PPG -25 -25 -41 **AdenoCa increasing Barrett’s. EGD 4—. -18 -16 Lower LES Pressure alc severe GERD. f. Long Term Complications of DM: ISGD +97 +27 +151 Pathogenesis GERD: fl tMircovascular disease Potpourri III... — LES incompetent George knew what he wanted in a woman... — **Inappropnate LES relaxation 2). t(Marcovascular) disease ‘The girl I marry will be an economist in the kitchen, an aristocrat in the living room and a GERD Diagnosis: a. Clinical Hx g. CAD Mortality in Type II: harlot in bed.” Now he’s married and his wife has all the b. Barium studies (Air contrast) c. Endoscopy — men: 2-3 x t death rate (Joslin) required traits—but not in the same order. She’s women: same after losing protection of an aristocrat in the kitchen, a harlot in the living d. Ambulatory pH monitor **Who estrogen (ie. post menopausal...) room and an economist in bed. to endoscope? a. GERD sy’s > Syrs Is insulin atherogenic? Ans: No Quotable Quotes b. age>40 HBAIc predicts CAD in Type II: Most people don’t mind criticism as long as it’s c. White male (never seen in blacks) 24° Ambulatory pH Monitor: Spikes below pH Hyperlipidemia- Hyperglycemia about someone else... (National Enquirer) 4- We all live every day in virtual environments 4.0 = reflux nsulin Resistance defined by our ideas. (Michael Crighton) 0 The world is progressing and resources are GERD Rx: Hypercoagulability-_ be Hyperinsulinemia coming more abundant. I’d rather go into a a. Life Style Modification — grocery store today than to a King’s banquet a 1). Elevate head while sleeping c 6 inch block under legs or wedge under mattress. h. Rx Cardiovascular Metabolic Syndrome: hundred years ago... (Bill Gates) 2). Modify diet: ,jvoiume & fat 1). Ameliorate hyperglycemia Doing the best at this moment puts you in the best 3). Avoid recumbancy 3 hrs pp 2). Improve lipoprotein place for the next moment... (Oprah Winfrey) 4). Stop smoking 3). Control hypertention In the Fast Lane 5). Antacids, alginic acid, 2HRA (OTC dose) I was heading for work on the freeway one B. Treatment of NIDDM: (Getting back on the morning when I noticed a car weaving slightly in b. Pharmaceutical Rx curve) the next lane. As I pulled even with it. I could see 1). Promotility Agents: a. Oral pharmacologic Therapy (5 classes) that the driver’s face was almost touching the - Bethanachol (Urocholine) I). Sulfonylurea (Most potent for HBAIc) wind shield as she used the rear view mirror to - Cisapride 2). Biguanides apply mascara. - Metoclopramide (Reglan) 3). Alpha Glucoside Inhibitors: Suddenly she veered in my direction... It scared - Domperodone (Acarbose) tid a.c.; effect on HBAIc; me so badly I dropped my lip stick right into my - Erythromycin ? start 25mg od and tup to tid: Max cup of coffee. (Catherine Lernm) 2). Acid Suppression: 50mg tid a). 2H Blockers 4). Thiazolidinedione Conference Notes... b). Acid Pump Inhibitors **F.oton 5). Repaglinide: (in Metformin failure) “GERD” VP Donald Castell MD. President Pump Inhibitors are the best agents Insulin secretagogue: adjunct to diet American GE Ass’n, Chm Department of Medi for controlling esophageal exposure in and exercise; use in combination with cine, Allgheny Univ of Health Sciences Fri Mar GERD... **GERD Metformin; enhances insulin secre 5 QMC healing dependant on level of acid tion: two to four times a.c./d control. *Metformin (US 4 yrs; Europe 40 yrs experience) Introduction: Lowers hepatic glucose production; insulin a. GERD: Sy’s or tissue damage 2° to reflux c. Surgery: 1). Hill repair 2). Belsay repair

HAWAIIMEDICALJOURNAL, VOL58, APRIL 1999 103 3). Nissen repair ***Laproscopic fundal plication Classified Notices ****Esophagitjs Relapses Quickly After Cessation of Therapy: Toplacea classifiednotice: *85% relapse within 6 mos after cessation of therapy.. .Therefore maintenance therapy important... HMAmembers—Pleasesend a signedandtype writtenadtotheHMAoffice.Asa benefitofmember ***Fundal plication: effective maintance for 2 years. ship,HMAmembersmayplacea complimentaryone timeclassifiedad inHMJas spaceisavailable. Omeprazole Trial: Effective GERD maintanance 5 yrs... Same results with 11 years of Rx. May need Nonmembers.—Pleasecall 536-7702for a non- to increase Omeprazole dosage: 20mg—4Omg—80mg daily memberform.Ratesare$1.50a wordwitha minimum of 20 wordsor $30. Notcommissionable.Payment Management of GERD: Endoscopy as guide to therapy. mustaccompanywrittenorder. Identify Barrett’s esophagitis: Office Space ***Surnep,1is not a nood diannostic test for GERD.

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