-
`
`The
`MERCK
`Manua\
`
`Of Diagnosis and Therapy
`
`.. Robert S. Porter, MD, Editor-in-Chief
`Justin L Kaplan, MD, Senior Assistant Editor
`
`Richard K. Albert, MD
`Marjorie A. Bowman, MD, MPA
`Glenn D. Braunstein, MD
`Sidney Cohen; MD
`Linda Emanuel, PhD ·
`Jan Fawcett, MD
`Eugene P. Frenkel, MD
`Susan L. Hendrix, DO
`Michael Jacewicz, MD
`
`Editorial Board
`Matthew E. Levison, MD
`JamesJeffrey Malatack, MD
`Brian F. Mandell, MD, PhD
`Gerald L' Mandell, MD
`Judith S;Palfrey, MD
`AlbertA. Rundio, Jr., PhD
`David A. Spain, MD
`Paul H. Tanser, MD
`Michael R. Wasserman, MD-
`
`., ·.'·
`
`.....
`
`:.
`
`•r;;:,.
`
`.
`Published by .
`MERCK SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC.
`.· Whitehouse Station, NJ ·.
`2011
`
`: •.''
`
`Page 1 of 7
`
`SENJU EXHIBIT 2067
`LUPIN v. SENJU
`IPR2015-01099
`
`

`
`Editorial and Production Staff
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`
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`
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`
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`ISSN 0076-6526
`
`Copyright© 2011 by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc.
`
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`Printed in the USA.
`
`Page 2 of 7
`
`

`
`Contents
`
`TAB '
`
`. · NO. ·
`
`. SEGION
`
`Guide for Readers ,
`Abbreviations
`Editors and Editorial Board .·
`··Consultants
`. Contributors
`
`:·
`
`.
`
`.·
`
`'
`
`' .
`
`' \
`
`•·
`
`'. .
`
`'.'
`
`.... -
`
`·.i:'
`
`. ·:·:, .·,'.
`
`Nutritional Disorders
`Gastrointestinal Disorders
`Hepatic and Biliary Disorders
`· Musculoskeletal and Conriective Tissue 'Disorders
`. ··-'"
`.
`. .
`Ear, Nose, Throat, and Dental Disorders
`. Eye Disorders
`-
`.
`Dermatologic Disorder~ ·
`Endocrine and Metabolic Disorde~s
`Hematology and Oncology . •
`.. .
`· lmml,lnology; ·AllergiC Disorders·
`.
`. ~ '-
`.
`: -~
`Infectious Diseases
`PsychiatriC Disorders
`Neurologic Disorders
`. Pulmonary Disorders,
`.· Cardiovascular Disorders·
`· Critical Care Medicine·
`Genitourinary Disorders
`: Gynecology and Obstetrics .
`Pediatrics • ·
`·. Ger!atri(:s
`<·· ··
`Clinical Pharmacology
`Injuries; Poisoning •·
`· .speciaiSubJects · .·
`Appendixes
`· · · ·
`·
`Ready Reference Guides .
`NcimaU,aboratory Val~es , •· ... , ,
`. : ,
`Trade Names of Some Commonly Used Drugs
`·Index
`
`2
`3
`· 4
`5
`6
`
`13
`14
`15
`
`•!
`
`.-,, •.
`
`PAGE
`
`viii
`IX
`'xi
`xiii
`XV
`
`,; 67
`
`203
`281,
`
`','
`
`'411
`535
`'629
`'755
`·•'. 915
`.1077
`1143
`·,'1483
`! 1583
`1823
`2015
`2243
`2303
`'' 2479
`~ ; 2691
`:~ 3069
`3165
`
`'
`
`-' .·: ')
`'·: ,·
`
`'
`
`': '3371
`•. 348,9
`
`3489
`349J
`' .
`3505
`3521
`
`.. ,. '; ,:;! ~~-
`
`Page 3 of 7
`
`

`
`3562
`
`Index
`
`.
`
`;
`
`i
`
`Casal's necklace 31
`Cascara 87
`in elderly 3101
`Caspofungin 1320, 1323:
`Cast 3203
`·
`Castleman disease 1394
`Castor bean poisoning 3337, ·. ·
`Castor oil 87
`Casts, urinary 2309, 2311, 2375
`Cataplexy 1704, 1712
`Cataracts 606-607
`congenital2920·
`..
`... · ··
`Catatonia 1541, 1560
`Catecholamines 791 (see also Epinephrine; ·
`Norepinephrine)
`· ,,
`in MEN 2A syndrome 912
`pheochromocytoma secretion of 801 ~803,·
`912
`urinary 802,3500
`Catechol 0-methyltransferase inhibitors
`1768, 1769
`:
`Catheterization .
`arterial2249-2250
`: .. ./ _;··
`bladder 2316-2317:
`·· • r•,
`in children 2845
`for incontinence 2359, 2362, 2364
`in-dwelling 2362
`infection and 2378.
`,;-;
`oliguria with 2252_:_2253, 2252
`in trauma 3192
`cardiac 2048-2052, 2050, 2051
`complications of 2051-'-2052 ··
`left-heart 2048
`right-heart2048, 2105,2205 ·
`centralvenous2247-2249,2249
`in cardiopulmonary resuscitation 2259
`for dialysis 2449 . <.c
`· infection and 1166 · :
`pleural effusion and 1998 · ,
`intra-abdominal abscess drainage with ' 1
`119
`,·,
`' ,,,
`··,
`I
`intracranial 2246
`peripheral vein 2247
`peritoneal2451
`pleural2001, 2003
`pulmonary artery 1986, 2244-2246; 2245,
`._•:.; .. :. ; ··,;
`2246
`. !
`in shock 2299,.2301
`urinary (see Catheterization,.IJladder) .··· ..
`CAT scan (see Computed tomography)
`Cat-scratch disease 469, 1158, 1244->-1245,
`1244 f,> ·.;.~. ·.:>,·. ;; :.; .
`':.'· ( ·:£:').( :·. t<-
`Cauda equina 1804
`· ·'
`,, .. : ,_,,, ...
`.: :, '
`
`... ::
`
`"
`
`,_,.
`· · ,,
`
`Caudaequina syndrome 1806, 3228,3228, '·
`3229'
`-;
`Cauliflower ear 3231
`Causalgia (complex regional pain syndrome)
`1633-1634
`Caustic ingestion 3335-'3336 ··
`gastritis with 133
`Cavernous hemangioma 976
`Cavernous lymphangioma 748.
`Cavernous sinus thrombosis 554, 560, ·
`624-625
`CEA (see Carcinoembryonic antigen)
`Cecum
`ameboma of 1368
`volvulus of 117
`Cefaclor 1187
`in otitis media 449
`Cefadroxil 1186
`in endocarditis prophylaxis 2200
`Cefazolin 1186.
`in endocarditis prophylaxis 2200
`in infective endocarditis 2198
`neonatal dosage of 2812
`as preoperative prophylaxis 3349-3350
`Cefepime 1188, 1202
`in infective endocarditis 2198,
`in meningitis 1739,.1740, 1741 ..
`neonatal dosage of 2813 ·;
`Cefoperazone 1187
`Cefotaxime 1187,1203
`in meningitis 1739, 1740,:1741
`neonatal dosage of 2813 ~ · · ·
`Cefotetan 1187
`Cefoxitin 1187 ·'
`Cefpodoxime 1188,1203
`Cefprozil1187
`Ceftazidime 1188, 1203
`. iri infective endocarditis 2198 · : ·
`in meningitis 1740, 1741 · ·
`•
`neonatal dosage of 2813
`Ceftibuten 1188 ·
`Ceftizoxime 1188
`Ceftobiprole 1202
`Ceftriaxone 1184, 1188, 1203
`in children 2761
`in infective endocarditis 2197-2198
`in Lyme disease 1271, 1271
`in meningitis 1739, 1740, 1741
`·. neonatal dosage of 2813 · ·
`· '
`in otitis media 449
`Cefuroxime 1187
`.in Lyme disease 1271 ·
`in otitis media 449 '·
`
`Page 4 of 7
`
`

`
`606
`
`SEQION 6 , Eye Disorders
`
`block. It is done as soon as the cornea is clear
`and inflammation has subsided. In some cases
`the cornea clears within hours of lowering the
`lOP; in other cases, it can take.! to 2 days. Be(cid:173)
`cause the chance ofhaving an acute attack iu
`the other eye is 80%, LPI is done on both eyes.
`The risk of complications withLPI is ex~
`tremely low compared with its benefits. Glare,
`which can be bothersome, may occur if.the.iri(cid:173)
`dotomy is not placed superiorly enough forthe
`upper lid to ~over it ·
`·
`
`Chronic angle-closure glaucoma: Patients
`with chronic; subacute, or interm.ittent angle(cid:173)
`closure glaucoma should also have LPI. Ad(cid:173)
`ditionally, patients with a narrow angle, even iu
`the absence of symptoms, should undergo
`promptLPI to prevent angle-closure glaucoma.
`The drug and surgical treatments are the
`same as with open-angle glaucoma. Laser tra(cid:173)
`beculoplasty is relatively contraindicated if the
`angle is so narrow that additional PAS may
`form after the laser procedure. .
`·
`
`~
`
`I
`
`'~~
`I'\' I
`' ' \ , I
`
`I
`
`'
`
`'
`
`·-
`
`_.,_
`
`(Fm deveiopmental or c~ngenital ~atar~~ts,
`seep. 2920.)
`·
`'
`'
`'
`A cataract is a congenital or degenerative opac(cid:173)
`ity of the lens. The main symptom is gradual,
`painless vision blurring. Diagnosis is by oph(cid:173)
`thalmoscopy and slit-lamp examination. Treat(cid:173)
`ment is surgical removal and placement of an
`intraocular lens.
`. Lens opacity can de~elop iu s~~~ral loc~ti~ns:
`· • Central lens' nucleus (nuclear cataract)
`• ~eneath the posterior lens capsule (paste(cid:173)
`, nor subcapsular cataract)
`· ·· · · ··
`
`distinguishing dark blue from bi~ck. Painless
`blurring eventually occurs: The degree of blur(cid:173)
`ring depends on the location arid extent of the
`opacity. Double vision occurs rarely. .
`.
`. · .. With a nuclear cataract (see Plate 4), dis(cid:173)
`tance vision worsens. Neai: vision may im(cid:173)
`prove in the early stages because of changes
`Ill t~e refractive index of the lens; presbyopic
`patients may be temporarily able to read with~
`out glasses (second sight):
`·
`·
`· ·• · : ·.·
`'. · A posterior subcapsular cataract dispropor(cid:173)
`tionately affeCts vision because the opacity is
`located at the crossing point of incoming light
`ta:ys. Such cataractS reduce visual acuity more
`wh~n the pupil constricts (eg, in bright light,
`dunng reading). They are also the type most
`likely to cause loss of contrast as well as glare,
`~specially from bright lights orfrom car head-
`•.·.
`'.
`' .·
`lights while driving at night. :.
`Rarely; ~e cataract swells, occluding the tra(cid:173)
`becular dramage meshwork arid causing sec(cid:173)
`ondary closed-angle glauco~a and pain.
`
`•
`
`•
`
`• ·
`
`·
`
`• • '
`
`Diagnosis
`.. c •
`• Op~th~o~copyfollowecl by slit-lamp ex~
`amrnation .
`· · · >
`'· Diagnosi~ is bes·t~~de' ~ith the• p~pil di~
`lated. W_ell-developed cataracts appear .as
`gray, whrte, or yellow-brown opacities in the
`l~ns. Examination of the red reflex through the
`dilated pupil with the ophthalmoscope held
`about 30 em away usually discloses subtle
`opacities. Small cataracts stand out as dark de(cid:173)
`fec~s in the red reflex. A large cataract may
`~bhterat~ the red reflex .. Slit-lamp examina(cid:173)
`tion ~rovides more details about the. character,
`location, and extentofthe opacjty: :,; \ .. ·<"
`Tre~tment · ·
`.
`
`• Surgical removal of the c~taract · ·: · ··
`• Placement of an intraocular lens ·· ·
`
`·
`
`''
`
`· ·
`
`• ;,
`
`Etiology
`Cataracts occur with aging. Other risk fac-
`· · ·
`tors may include the following: ..
`~. Traurria (~6m~ti;ne~ cau~irig du;;a~ts Y~ars
`. later) . . . ·
`·
`,· ·..
`· · ·.
`· · · · ,
`"
`• Smoking . ·,. ·
`: •. Alcohol use
`. .
`.
`; ·~ Exposure to x -~ay;'
`.
`· · · · •.
`... ~ Heatfr?~ ~nfrared exposure ...•
`• Syst~~Ic dis.ease (eg, diabetes)·
`• Uveitis .
`·· . .
`·
`• System.ic drugs (eg, c~itiwster~id~) ·.
`, .• Undernutrition . .
`.·. ,
`·.
`· ·•
`· '
`:.• Dark'eyes ,
`... · •·. · ·
`' ·
`.. • Po~s~bly chronic ultraviolet~~po~ure ..
`, ·Many people have rio risk factors otherth;~
`a&'e. Some cataracts are congenital, associated
`WI,th numerous syndromes and diseases.
`'.· .
`.
`.
`·::•,. ',
`.
`Symptoms and Signs
`.
`.
`·,Cataracts generally develop slo~ly over
`years. Early symptoms may be loss of contrast
`glar~ (hal()s a~d starbursts around lights):
`needing more light to see well,, and problems
`
`·-
`
`~
`
`,
`
`.
`
`, . . .
`
`' _,
`
`.
`
`" I
`
`, ~ .
`
`'
`
`Page 5 of 7
`
`

`
`st+· &ii'jtrrmW TRW
`
`Frequent refractions and corrective lens
`prescription changes may help maintain useful
`vision during cataract development. Occa(cid:173)
`sionally, long-term pupillary dilation (with
`phenylephrine 2.5% q 4 to 8 h) is helpful for
`small centrally located cataracts. Indirect light(cid:173)
`ing while reading minimizes pupillary con(cid:173)
`striction and may optimize vision for close
`tasks. Polarized lepses reduce glare. ·· ·
`Usual indications for surgery. include the
`following:
`,'
`· ·
`·
`·
`.
`' .
`. • Best vision obtained with glasses is .worse
`than 20/40 ( < 6/12), or vision is signifi(cid:173)
`cantly decreased under glart< conditions
`(eg, oblique lighting while trying to read a
`chart) in a patient with bothersome halos or
`starbursts.
`.
`.
`.
`. · . . . . ,
`·
`• Patients sense that vision is limiting (eg,
`by preventing activities of daily living
`such as driving, reading, hobbies, and
`occupational activities).· · ·
`· .. ·
`• Vision could potentially be meaningfully
`improved if the cataract is removed (ie, a
`significant portion of the vision loss must be
`caused by the catil!act }. •··
`Far less. common indications include cata(cid:173)
`racts that cause glaucoma or that obscure the
`fund~s in patients who need periodic fundus
`exarnmations formanagement of diseases such
`as diabetic retinopathy and glaucoma. There is
`no advantage to,renioving a cataract early.·
`·
`~ataract extraction is usually done using a
`topical or local anesthetic and IV sedation.
`There are3 extraytiori techniques: In intra(cid:173)
`capsular cataract extraction the cataract
`and l~ns c~psule are removed in ~ne piece; this
`technique 1s rarely used.lri extracapsular cata(cid:173)
`ract extraction, the hard central nucleus is
`~emoved in one piece and then the soft cortex
`~ remov:d in I_UU!tipte small pieces~ Iri pha(cid:173)
`. oe~uls1ficatwn, the hard central nuCleus
`IS diSSOlved by ultrasound imd then the SOft
`~rtex is reJ?ove.d in multiple small pieces.
`. ~CoemuJsJficatiOfl requires the smallesrin(cid:173)
`CiSJOn, thus enabling the fastest healing and is
`fsually the preferred procedure. In extr;capsu~
`
`t extractio~ and phacoemulsification, the
`·
`• .
`·
`·.
`ens capsule Is not removed. , ·
`· A plastic or silicone lens is al~ostalways.
`Irnpla t d ·
`· ·
`·
`.
`·
`· ·
`1 fn e . mtraocularly to replace the opti-
`ca . oc~smg power lost by removal of the
`cry! stallme lens. The lens_ implant. is usually
`Pacedonorw"th" h' I .
`1 m t e ens capsule (posterior
`ch b
`·
`fro~~o~r~e~s~. Thele~s can also be placed in
`tach d t em~ ~antenor chamber lens) or at-
`e t~,the Ins and ~ithin the pupil (iri~
`
`' . CHAPTER 66 . Cataract
`
`607
`
`plane lens)'. Iris plane lenses are rarely used in
`the US because many designs led to a high
`frequency of postoperative complications.
`Multifocal intraocular· lenses ·are newer and
`have. different focusing zones that may re(cid:173)
`duce dependence on glasses after surgery. Pa(cid:173)
`tients occasionally experience glare or halos
`with these lenses, especially under low-light
`conditions.
`· ·
`In most cases, a tapering schedule of topical
`antibiotics (eg, moxifloxacin 0.5% 1 dropqid)
`and topical corticosteroids (eg, prednisolone
`acetate I% 1 drop qid) is used for up to 4 wk
`postsurgery. Patients often wear an eye shield
`while sleeping and should avoid the Valsalva
`maneuver, heavy lifting, excessive forw(lrd
`bending, and eye_rubbing for several weeks.
`Major complications of cataract surgery are
`rare. Complications include the foll()wing: • ,
`
`~Intraoperative: Bleeding beneath the ret(cid:173)
`ina, causing the intraocular contents to
`· ·extrude through the incision (choroidal
`hemorrhage), vitreous prolapsing out of
`the incision (vitreous loss), fragments of
`the cataract dislocating ihto the vitreous,
`incisional bum, and detachment of corneal
`endothelium and its basement membrane
`(Descemet's membrane)·
`..
`• Within the· first we~k: · Endophthalmitis
`· (infection within the eye) and glaucoma
`• Within the frrst month: Cystoid macular
`edema
`··
`·
`· ·
`· · ·
`·
`• Months hiter: Bullous keratopathy (ie, swell(cid:173)
`ing of the cornea due to damage to the core
`neal pump c~lls during cataract surgery),
`retinal detachment, and posterior capsular
`opacification (common,· but treatable with
`·
`·
`·
`·
`·
`·
`·
`· ·
`laser)
`· ~·
`
`After surgery, vision returns to 20/40 (6112)
`or better in 95% of eyes if there are no preex(cid:173)
`isting disorders such as amblyopia, retinopa(cid:173)
`tl}y, macular.degeneration, and glaucoma. If
`an intraocular lens is not implanted, <:;ontact
`lenses or thick glasses are needed to correct the
`resulting hyperopia. .
`·
`'
`
`Prevention
`Many ophthalmologists recommend ultra~
`violet-coated eyeglasses or sunglasses as a
`preventive measure. Reducing risk factors such
`·as alcohol, tobacco, and corticosteroids and
`controlling blood glucose in diabete~ delay
`onset. A diet high in vitamin C;vitaminA, and
`carotenoids (contained .in vegetables su'ch as
`spinach and kale) may protect against cataracts.
`..
`..
`. :
`. .
`·-
`.
`.
`.
`
`',
`
`/
`
`f ~
`f i~
`
`I f
`f
`4 f
`,-· '4
`
`Page 6 of 7
`
`

`
`if'l't&'b ·it g; gggg
`
`4 ,;
`
`2920
`
`SEOION 19 Pediatrics
`
`···Treatment should be directed by an oph- ·· ·
`thalmologist. Any underlying causes must be
`treated (eg, eyeglasses or contact lepses to
`correct refractive error; removal Of a cataract).
`Use of the amblyopic eye is then encouraged
`by patching the better eye or by administering
`atropine drops into the better eye to provide a
`visual advantage to the amblyopic eye. Ad(cid:173)
`herence to treatment is better with drop ther(cid:173)
`apy. Maintenance treatment fqr prevention of
`recurrences rriay be recommended after im(cid:173)
`provement has stabilized, until a child is
`about 8 to 10.
`·
`· · ··
`··
`·
`
`CONGENITAL-CATARACT'
`(Infantile Cataract)
`Congenital cataract is a lens opacity that is present
`at birth or shortly after birth.
`·· , . ,_,/
`.,
`
`· Congenital cataractS may be sporadic, or they
`may be caused by chromosomal anomalies,
`metabolic-disease (eg; galactosemia), or in~
`tr'auterine infection ( eg; rubella) or other rna~
`ternal disease during pregnancy. Cataracts
`may be located in,the center of the lens (n:u.:
`clear), or they may involve the lens rnaterial
`underneath the anterior or' posterior lens cap-'
`sule (subcapsular or cortical). They may be
`unilateral or bilateral. They may not be no(cid:173)
`ticed unless the red reflex is checked or unless
`ophthalmoscopy is dorie at birth, As with other
`cataracts, the lens opacity obscures vision:Tat-'
`aracts may obscure the view of the.optic disk
`and vessels and .should always be evaluated
`byan6phthalmolog1st.' •'-·':~·-. ·
`-~ .·
`" ·Removal of a cat!micFwithin 17 wk after
`birth permits the developmetifofvision and
`cortical visual pathways. Cataracts are removed
`by aspirating them through a small incision,
`IIi many children, an intraocular lens'niay pe
`implanted> Postoperative visual 'correction
`with eyeglasses, contact lenses; ofboth is usu~
`ally required to achi<,we the best outcome,_, _,,
`After a unilateral cataract is removed, the
`quality of the image in the treated eye is ipf~­
`rior to that of the other eye' ( assur'ning the Other
`eye is normal). Because the better ey~ is prec
`ferred,. the brain suppresses the pooret -quality
`iinage, and amblyopia( see p.•2919) develops.
`Thus, effective amblyopia therapy is neces.:
`saryfor the treated eye to develop normal sight.
`Some children are unable to attain good visual
`acuity because of accompanying structural de(cid:173)
`fects:·In·contrast, children with bilateral cata(cid:173)
`ract removal in:which image quality is similar
`il! bo.th eyes more frequently devel?p_equal vi"
`sron rn both-eyes.,,._ .• ,_,'"''" , ... ••> :. :
`.. ·.;;··,;
`Some cataracts are partial (posterior lenti"
`conus) and opacify during the 1st decade of
`
`life. Eyes with partial·cataracts have a better
`visual outcome.
`:. . .,
`.
`.. -
`:
`PRIMARY INFANTILE''
`;GLAUCOMA .. ' :. · ,,
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`·(Infantile Glaucoma; Congenital : :.
`Glaucoma; Buphthalmos)
`Primary infantile glaucoma is a rare develop(cid:173)
`mental. defect in the iridocomeal filtration angle
`of the anterior chamber that prevents aqueous
`fluid from' properly draining from the eye. This
`obstruction ·can cause increases in the intra(cid:173)
`ocular pressure; which if untreated can damage
`the optic nerve.
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`The disorder occurs in infants and young
`children and may be unilateral ( 40%) or bilateral
`(60%). Intraocular pressure increases above the
`normal range (10 to 22 mmHg). Glaucoma
`can also: occur in infants after trauma or in(cid:173)
`traocular surgery:(eg, cataract extraction).
`Glaucoma associated with aniridia or Lowe
`syndrome or Sturge-Weber syndrome is called
`secondary-glaucoma::;:>>
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`The eye becomes enlarged because the col(cid:173)
`lagen of the sclera and cornea can stretch from
`the. increased intraocular pressure~ Thelarge(cid:173)
`diameter (> 12 mm) cornea is thinned and
`sometimes cloudy. The infant may have tearing
`and photophobia. If untreated, corneal clouding
`progresses, the optic nerve is damaged (as ev(cid:173)
`idenced clinically by optic nerve cupping), and
`blindness may occur. Early surgical interven(cid:173)
`tion ( eg, goniotomy; trabeculotomy; trabec,
`ulectomy) is the mainstay of treatment.·.·· ..
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`'''~,~STRABISMUS ..
`Strabismus is misalign~ent of the eyes, whic~
`causes deviation from the parallelism of normal
`gaze. Diagnosis is dinica~ induding obServation of
`the romeallight reflex and use of a cover test
`Treatment ·may indude mrrection ·of visual impair,
`ment vvith patching and corrective I~ alignment
`by cOrrective lenses, and surgical repair. .
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`. . Str~bismd~ '~c~~;:i~ ~b~ut 3% ()J' children.
`Although most strabismus is caused by re(cid:173)
`fractive errors or muscle ·imbalance, rare causes
`include. retinoblastoma or :other· serious Dcular
`defects and rieuroiogic disease; Left untreated,
`about .SO% of children with strabismus have
`somevisualloss due to ainblyopia (seep. 2919).
`:, . Several varieties of strabismus have been
`described based ori direction of deviation;
`specific c~nditions under. which deviation ·
`occurs and whether deviation is constant or
`interrn'ittent. Description of these varieties
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`requires the definition of several terms.
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