TYPHLITIS, PERITYPHLITIS, PARATYPHLITIS.

BY JAMES T. WHITTAKER, M.D.


HISTORY.—Typhlitis ([Greek: typhlos], blind), inflammation of or about the head of the colon, more especially the vermiform process, is a disease of modern recognition. Individual cases had been reported as curiosities where foreign bodies or fecal accumulations had excited inflammation in this part of the intestine, but it is undoubtedly to Dupuytren1 that the credit is due of having first individualized this disease as a separate affection. About the same time (1827) Longer Villermay published his communications in the Archives gén., t. v. 246, on the diseases of the vermiform process, to be followed in the same year by Mêlier2 and Hussar and Dance with observations on inflammation of the connective tissue in the region of the cæcum. These affections, which had been hitherto described as inflammatory tumors in the right iliac region, now received from Puchelt3 the distinct name perityphlitis.

1 Leçons oral de Cliniq. chirurg., t. iii. art. xii.

2 Arch, gén., Sept., 1827.

3 Heidelberg klin. Annal., i. 571 and viii. 524.

Perhaps the most remarkable events in the history of these affections since this time are the contributions of Stokes and Petrequin (1837) on the value of opium in the treatment of perforation of the vermiform appendix, of Albers,4 who first distinguished the special form of typhlitis stercoralis, and of Oppolzer (1858-64), who set apart, perhaps as an unnecessary refinement in differential diagnosis, a paratyphlitis, an inflammation of the post-cæcal connective tissue. Matterstock5 (1880) deserves especial mention for having given such prominence to anomalies of the vermiform appendix in the etiology of the affection; and Kraussold6 (1881) has connected his name with the therapy of the disease by the boldness with which he expresses his convictions regarding the necessity of early evacuation, by incision, of inflammatory products, as first practised by Willard Parker in 1843.

4 Beobacht. aus dem Gebiete der Pathologie, ii. 1.

5 Handbuch d. Kinderkrank., Bd. iv. p. 893.

6 Volkmann's Sammlung., No. 191.

GENERAL REMARKS.—Typhlitis, strictly speaking, is limited to affections of the cæcum and its appendix vermiformis; perityphlitis is mostly due to extension of the inflammation to the peritoneal envelope of these organs; while paratyphlitis signifies an involvement of the extra-peritoneal and post-cæcal connective tissues. Both perityphlitis and paratyphlitis are therefore secondary processes, though they may, in exceptional cases, arise from affections of organs other than the cæcum, as from perinephritis, psoitis, vertebral caries, or as an expression of metastatic processes in pyæmia, septicæmia (puerperal fever), typhoid fever, etc.

ETIOLOGY.—Typhlitis and its allied affections or complications show especial predilection for the male sex and the period of adolescence. Nearly three-fourths (733) of the whole number (1030) of cases of perityphlitis collected from the literature by Matterstock were males, and this proportion holds good in infancy and early youth as well as in adolescence. The greatest number of cases, 33 per cent., occurred at the ages of 21-30; next, 30 per cent., at 11-20; while the ratio gradually decreases toward both extremes of life. So the opinion is expressed with singular unanimity by all authors that these diseases pre-eminently affect the bloom of life.

The observation that typhlitis has so often been found to arise from disease of the vermiform process has led to a closer study of its anatomical relations, and developed the fact that this organ is subject to great variation in size, shape, and situation.

Normally, the appendix vermiformis arises from the posterior interior aspect of the cæcum as a tube of the diameter of a goosequill and a length of three to six inches, with a general direction upward and inward behind the cæcum. It is commonly provided with a small mesentery, which retains it in its place. Its cavity communicates with the cavity of the cæcum by a small orifice which is at times guarded by a valvular fold of mucous membrane, while its free closed end terminates abruptly in a blunt point. It is commonly found filled with mucus throughout its entire length. The existence of this superfluous structure, which is found only in man and certain of the higher apes, has given rise to much speculation among the anatomists and physiologists, especially of the teleological school, as to its possible use. It is now, however, the generally acknowledged opinion that the appendix vermiformis is a relic or rudiment of a subsidiary stomach in lower forms of life. The head of the large intestine, which forms almost an additional stomach in the Gramnivora, and is three times the length of the whole body in the marsupial koala, is very much reduced in the Carnivora, whose food contains but little indigestible matter, and is greatly reduced in the Omnivora, as in man. The vermiform appendix is the shrivelled remnant of the great cæcal receptaculum of the lower animals. In the orang it is still a long convoluted tube, but in man it is reduced, as stated, to the size of a quill three or four inches in length, and is often entirely absent.

Kraussold, who complains that the vermiform process has hitherto received only step-motherly treatment at the hands of anatomists and clinicians, undertook a series of investigations which went to show how often and what extreme anomalies do occur. In some cases the appendix was disposed in an exactly opposite to the normal direction, its blind end being turned upward along the ascending colon. In one case it was found wound about the ileum; in another, spirally turned at its end and lightly adherent to a hernial sac. Sometimes it was abnormally long or short, open or closed with a valve, cylindrical, saccular, or bulbed, fixed or free, curved or bent upon itself at a sharp angle, provided with a short mesentery, and sometimes, as stated, it was entirely absent.

But by far the most interesting point connected with this organ was the frequency with which it was found the seat of ulceration or stricture from cicatrization somewhere in its course, the result of dysentery, typhoid fever, syphilis, and more especially of tuberculosis. Clinicians who have been struck with the frequency with which typhlitis has occurred in tuberculous subjects find in this discovery a satisfactory explanation of this very remarkable coincidence.

Normally, the vermiform appendix is found filled, as stated, with a tough vitreous mucus, but not infrequently masses of feces, foreign bodies, intestinal worms, etc. find their way into it, where they may remain innocuous or may excite a dangerous inflammation. This fact, in connection with the general uselessness or superfluousness of this structure, has led pathologists to characterize the vermiform process with the significant appellation of a death-trap.

Two anatomical factors deserve especial emphasis in explanation of the frequent origin of disease in the vermiform appendix. One is the existence of the valvular fold of mucous membrane, already mentioned, at or near the orifice of the tube in the cæcum, the clinical importance of which was first pointed out by Gerlach. This fold is most marked between the ages of three and twelve, and when pronounced narrows the orifice to one-half or one-third of the whole calibre of the tube. As a rule, this fold, and the consequent diminution in the size of the orifice, are but little marked in the first years of life and in old age, which accounts for the relative infrequency of typhlitis at these periods of life.

The second mechanical factor is the deformity caused by the abnormal anatomical position of the organ, either as a congenital defect or as a pathological change. Matterstock quotes from Züngel, who observed in 59 cases in the Hamburg hospital whole or partial obliteration 30 times, catarrh and old fecal concretions 43 times, abnormal adhesions 12 times, and tubercular ulceration (without perforation) 11 times. Toft claims as the result of 300 personal investigations that every third person between the ages of twenty and seventy showed the traces of present or past inflammation, and that actual ulceration existed in 5 per cent. of all bodies examined. Kraussold declares that this percentage is rather too low than too high, and adds that among his patients—who were, it should be stated, mostly phthisical—it was remarkable how extraordinarily often the whole vermiform appendix was the seat of an encroaching ulcer. In a number of cases cicatrices or cicatricial alterations were found where typhoid fever or dysentery had existed in the previous history.

Attention should at least be called to a last anatomical factor in explanation of the frequency of ulceration and inflammation of this structure, in that its walls are so sparsely endowed with muscular tissue as to render it unable to empty itself of the virus or germs of disease which enter it from the comparatively stagnant reservoir, the cæcum.

Constipation is usually invoked as a cardinal factor in the genesis of typhlitis (typhlitis stercoralis). Speck calls attention to the frequency of the disease in East Siberia, where the food, mostly vegetable, contains a large amount of indigestible residue. But that this condition cannot sufficiently account for the disease in most cases is proved by the fact that constipation is more frequent in advanced life and among females, in whom typhlitis with its associate lesions is more infrequent. For the same reason a sedentary mode of life loses force as an argument in its production. Perhaps the most efficient cause of the condition is a local paresis of the muscular tissue of the cæcum produced by the irritation of intestinal catarrh, of disease virus, of a fecal concretion or a foreign body—an irritation which may induce first a spasmodic action, and subsequently, as a result, a partial paralysis or a paresis. The same condition may be brought about more directly by the presence of a centre of irritation—viz. by reflex inhibition of innervation. Accumulation and impaction of feces must then necessarily ensue, and it is highly probable that this accumulation occurs in this way as a result more frequently than as a cause of the condition. For the symptoms of a simple accumulation of feces (coprostasis) are never so severe, at least at the start, as to mark the onset of a genuine typhlitis. Nor is there anything in healthy feces to induce the signs of a severe blood-poisoning which so commonly announces the advent or course of typhlitis.

Room is here open for the surmise that most cases of typhlitis pur et simple are due to the presence in the cæcum of the germs or virus of disease taken with the food or drink, and traversing innocuously the whole length of the alimentary tract, to finally bring up in this most stagnant part of the intestinal canal.

The rôle of pure mechanical causes cannot be ignored or underrated in perityphlitis, understanding by this division processes which commence in the vermiform appendix. For it is the rule to discover in the vermiform appendix in these cases either fecal concretions or foreign bodies. Haeckel and Buhl found concretions of meconium in a new-born child, and fecal concretions, intestinal stones, are far more frequently encountered than foreign bodies. In 146 accurately observed adult cases recorded by Matterstock, fecal concretions were met with 63 times, foreign bodies 9 times, while in the other cases nothing could be discovered; and in 49 cases among children, fecal concretions were discovered 27 times, foreign bodies 3 times, and nothing abnormal in the remaining cases. Not infrequently a small foreign body acts as a centre of crystallization for feces which become superimposed in successive layers. Hairs, as of the beard, sometimes officiate in this way. Among other foreign bodies met with in fatal cases of perforation, independently of feces, may be mentioned round-worms (Faber), cherry-stones (Paterson), needles (Payne), fish-bones (Züngel), gall-stones (Hallete), a mass of ascarides (Klebs), buttons (Gerhardt), etc., etc. As already intimated, supposed foreign bodies are often found on examination to be nothing else than intestinal concretions. As to cherry-stones, which are so often accused of producing typhlitis, Biermer and Bossard found it difficult or impossible to force them into the vermiform process.

MORBID ANATOMY.—The lesions revealed upon the post-mortem table show for the most part the ordinary picture of perforative peritonitis, which is by far the most frequent cause of death. The peritoneum in the vicinity of the perforation is found hyperæmic, swollen, necrosed, covered with flakes of soft fibrin, or partially agglutinated to contiguous structures. The wall of the bowel is very much thickened by catarrhal swelling of its mucosa, proliferation of its submucous tissue in more chronic cases, oedema of all its coats, or suppurative processes. Not infrequently the mucous tissue is the seat of extensive ulceration which may involve other structures of the gut or form an abscess, even as large as a man's head, in its immediate vicinity. The abscess may remain strictly localized or may wander to discharge itself into the ileum, cæcum, duodenum, and diaphragm (Bamberger) with resultant empyema (Duddenhausen), colon (Prudhomme), bladder (Bossard), in which case the fecal concretion became the nucleus for a vesical stone; acetabulum (Aubry), inferior vena cava (Demaux), or peritoneal cavity, the most frequent eventuality. Duddenhausen saw in one case a pylephlebitis result, Von Buhl a pylephlebitis and metastatic liver abscess, which condition, Matterstock says, is noted 11 times in 146 autopsies; and older writers speak of discharges into the pleural sac, into the lungs, pericardium, uterus, vagina, etc. A curious case was observed by Eichhorst in Frerichs' clinic, where pus found escape through the umbilicus. So cases of burrowing sinuses with abscesses at distant seats, as in the groin or lumbar region, fistulæ with continuous discharge, and other curiosities, may be found among the records by the curious.

In cases of more acute course the lesions are often found centred about the vermiform appendix. The most various contortions, adhesions, or erosions are observed in this structure. Occasionally a constriction occludes the course of the tube, while the distal end is dilated into a condition of hydrops. It may be found perforated in one or in several places. The cicatrices or agglutinations of old attacks may be encountered; it may be cut in two or three pieces (Matterstock), or have been entirely absorbed. Kraussold records a case of this kind in a colleague who died of typhlitis. Upon the post-mortem table no trace of the vermiform appendix could be encountered except a dimple on the mucous surface of the cæcum, indicating the site of its former orifice.

SYMPTOMATOLOGY.—Typhlitis announces itself in two ways—suddenly and insidiously. In adults the disease begins as a rule with violent signs; in children there is often a prodromatous stage which may last for days or for months before a positive diagnosis can be established. There are in these cases anorexia and vomiting, constipation and diarrhoea, colicky pains, mostly concentrated about the ileo-cæcal region. There are at this time a disinclination to stand or walk, a stooped posture or gait, occasionally a light icterus, a feeling of formication or paresis in the right leg, and lastly an increased resistance or a palpable tumor in the right ileum.

In the adult the disease is wont to begin with more tempestuous signs. Not infrequently it is ushered in with a well-marked chill, upon which immediately supervenes a sharp pain at the affected region. A general collapse of strength soon follows, with fever, thirst, a husky voice, a coated tongue, vomiting, singultus, and an expression of anxiety. The impression of serious illness becomes apparent at once. The case early bears the aspect of a grave infectious disease. A constant, dull, boring, gnawing, or lancinating pain in the right iliac region first excites the suspicion of the physician as to the real nature of the disease. In children the pain is sometimes felt first in the epigastrium; in three cases mentioned by Büchner, Herzfelder, and Traube it was first experienced in the left ileum. There may be at this time no tumor, but there is increased resistance to pressure and exquisite tenderness to touch in the neighborhood of the cæcum. The whole abdomen is more or less tender, and often tumid. If there should be also gurgling from displacement of gas, doubt is excited as to the possible existence of typhoid fever.

In the course of a few days the tumor takes shape. A typhlitis stercoralis shows a distension of the whole ascending colon, a sausage-shaped tumor, smooth or nodulated, along the entire right side of the abdomen, with increased resistance also in the transverse colon. More frequently in typhlitis—and, as a rule, in peri- and paratyphlitis—the tumor or tumefaction is more localized about the head of the colon. Frequently the swelling is so great as to be visible as a protrusion or bulging of the affected region. Percussion shows dulness, tanquam femoris, in cases of pure typhlitis, whereas in peri-, and more especially in paratyphlitis, there is tympanites on light and dulness only on deep percussion. Palpation or palpatory auscultation occasionally, though very rarely, reveals a peritoneal friction sound (Gerhardt).

The third cardinal symptom of the disease is the disturbance of digestion, which, as stated, often precedes or attends the first manifestation of the pain and the tumor. Anorexia, nausea, and vomiting—which is in the last stage of the disease often substituted by singultus—present themselves as occasional or constant signs of the disease. Constipation remains as a rule throughout the whole course of the disease with an obstinacy which sometimes excites apprehension of an intestinal occlusion; or the constipation may alternate with diarrhoea or dysenteric phenomena, more especially in the earlier stages. The tongue is, as a rule, heavily coated, or in typhoid states is dry, glazed, or fissured, and sordes covers the teeth and gums.

Fever is not a necessary factor in typhlitis, but when present distinguishes itself by its irregular range. The pulse is usually accelerated, full, and hard; the skin is dry and harsh; the urine is scanty and high-colored, and contains "almost without exception unusually large quantities of indican" (Eichhorst).

Perforation, when it occurs, is usually recognized at once by the signs of more or less immediate collapse, which quickly results in death.

The abdomen becomes suddenly distended, meteoric over its entire surface, the normal hepatic dulness giving place to a tympanitic resonance.

Not infrequently perforation occurs as the result of an accident, as after a push or blow upon the abdomen (Volz), heavy lifting (Volperling), riding in a wagon (Marsh), after dancing (Cless), mere turning of the body in bed (Langdon Downs), after emesis (Urban), purgation (Stokes), enema (Mêlier), etc., etc. That the slightest agitation may suffice at times to break down the last barrier of serous tissue separating the intestinal and peritoneal cavity is shown in the case recorded by With, where fatal perforative peritonitis occurred after a fit of immoderate laughter.

Paratyphlitis distinguishes itself from the other forms of the disease by its more insidious character. There is also in paratyphlitis, as a rule, less disturbance in the alimentary canal. The cæcum in paratyphlitis is mostly empty or is filled with gas, whose presence is recognized by tympanitic resonance on lighter percussion. On the other hand, paratyphlitis is characterized by the greater frequency of pressure signs in the right lower extremity. If the subjacent iliac and psoas muscles be implicated, the thigh is flexed upon the leg in decubitus. Various paræsthesiæ, formication, numbness, pain, and veritable paresis are experienced in the right leg. Dysuria, retraction of the testicle, and priapism may also occur in this form of the disease. Or pressure upon the iliac vein induces thrombosis, with oedema, milk leg. The long-continued process of suppuration in paratyphlitis leads also at times to hectic fever or pyæmia, with slow marasmus.

In all cases relapses are very frequent, as repeated occurrences of the disease constitute the rule. Eichhorst records the case of a court-officer who suffered five attacks of paratyphlitis in the short space of one and a half years.

DIAGNOSIS.—The recognition of the disease is mostly simple. The pain, the tumor, and the disturbances of digestion sufficiently, and for the most part sufficiently early, distinguish the affection.

Simple impaction of feces is differentiated by the history of constipation; by the feel of the hardened feces, which form an elongated, nodulated, sausage-shaped tumor along the entire ascending colon, and later in shifting along the transverse colon; by the comparatively slight tenderness; and by the entire relief which follows thorough irrigation of the bowel.

Cancer may be eliminated by regard of the age of the patient, the slow development and course of the symptoms, and the gradual manifestation of its cachexia.

Invagination is an affection for the most part of early childhood—is marked by the sudden appearance of violent symptoms of disturbance of digestion, vomiting, often stercoraceous, occlusion, diarrhoea, or dysentery, with straining and discharges of blood.

DURATION.—Typhlitis and its complications have no definite duration. A case may terminate fatally in the course of a few days or may extend itself over months, or with its effects over years or for life. The disease is, as a rule, much shorter in childhood than in adult life. According to Matterstock, nearly one-half (44 per cent.) of children succumb to the disease within the first three days. Wood records the case of a girl aged ten who died in nine hours. The average duration of cases of typhlitis without suppuration ranges from fourteen to twenty-one days. The early evacuation of inflammatory products by aspiration or incision may cut the disease short at any time, or exacerbations and remissions may manifest themselves for months or years—a condition especially liable to occur when burrowing sinuses or fistulæ develop, or when passive encapsulated abscesses are aroused into activity by some accident or indiscretion on the part of the patient.

PROGNOSIS.—A case of typhlitis stercoralis has no gravity, and should terminate or be terminated within twenty-four to forty-eight hours after its recognition. Neglected or unrecognized cases, however, are not infrequently fatal from the circumscribed or more especially diffuse peritonitis which may ensue.

Typhlitis independent of fecal impaction is always a grave affection, requiring in every instance a very guarded prognosis.

Every form of typhlitis is more fatal in childhood than in adult life, and any case of the disease may present grave complications or assume a dangerous form at any time. The greater danger of childhood lies in the greater liability to peritonitis. Most subsequent writers confirm this statement, first made by Willard Parker, who also remarked that suppurative processes, abscess formation, is more common in the adult. The mortality of perityphlitis alone in childhood is 70 per cent., in adult life 30 per cent., so that the proportion of recoveries is exactly the reverse of these figures at the different periods of life.

The general adoption of the opium treatment has, however, rendered the prognosis of typhlitis far more favorable—has, in fact, reduced the mortality in adult life from 80 per cent., the appalling figures of the older statistics (Volz), to 30 per cent., the ratio of modern times.

The means of earlier detection and readier relief of accumulated pus have also contributed much to reduce the mortality of typhlitis. In 1872, Bull of New York had to report of 67 cases of perityphlitic abscess collected by him, mostly treated without operation, a mortality of 47½ per cent., while ten years later (1882) Noyes of Providence was able to report of 100 cases treated by operation a mortality of only 15 percent. (Pepper7).

7 "Contribution to the Clinical Study of Typhlitis, etc.," Trans. Med. Soc. Penna., 1883.

The development of fistulæ or wandering abscess, the occurrence of pyæmia and peritonitis, necessarily aggravate the prognosis of a simple case. Perforation is fatal of necessity, yet cases are not wanting where recovery has occurred even after this gravest of all the accidents of the disease. Thus, Patschkrowski reports, from Frerichs' clinic, a case of recovery after perforation, and Pepper mentions the results of an autopsy made upon an old man who died of vesical hemorrhage, in whom he "found that there had, at some unknown previous time, been perforation of the appendix."

PROPHYLAXIS.—The prevention of typhlitis has reference more especially to cases of habitual recurrence of the disease in adults, or to the earliest, prodromatous, stage in childhood. The slightest manifestation of pain in the right iliac region should be looked upon with suspicion in these cases, and absolute rest enjoined at once. Since in childhood perforation has occurred in insidious cases after so slight an irritation as a laxative or an enema, or even after a bath, every provocation of this kind should be avoided. Injunction is to be put upon all solid food in all cases in the inception as well as throughout the course of the affection, that the element of coprostasis be not superadded to the irritation of the disease. Adults subject to frequent recurrences or relapses will thus avoid also the development or aggravation of an intestinal catarrh, which in other cases of trivial import may become dangerous to them. Many cases of typhlitis are doubtless aborted at the start by the observance of absolute rest and abstinence from food or rigid diet at the start.

TREATMENT.—Perhaps no disease requires such careful consideration of its cause or form, inasmuch as the different varieties call for entirely different treatment. A typhlitis stercoralis, for instance, requires an exclusive evacuant treatment, whereas a peri- or paratyphlitis demands a treatment that shall put the bowels at rest.

The safest and most effective method of emptying the cæcum of impacted feces is by irrigation of the bowels by means of the funnel syringe devised by Hegar. The patient is put in the knee, elbow, or chest posture, and warm water—which is the best solvent for hardened feces—is allowed to slowly inundate the whole tract of the colon, after the manner and with the precautions already pointed out in the article on dysentery. Feeble or reduced patients should be supported in this posture until as much water as possible is slowly introduced. As a rule, a single thorough irrigation will suffice, or one or several additional operations may be required to secure the desired effect. At the same time, broken doses, twenty grains, of sulphate of magnesia may be administered every hour or two, not so much for the purpose of exciting additional peristalsis as of turning water into the intestinal canal from above.

The other varieties of the affection call for opium at the start, with the double view of preventing the irregular, spasmodic, or tetanic contraction of the muscular coat and of obviating the danger of peritonitis. Opium is not contraindicated in these cases, even if the element of fecal impaction be superadded, as all clinicians are familiar with the fact that the bowels will move of themselves at times even under its full narcotic effects.

The remedy is best given in fluid form, as in the tincture, that the dose may be graduated in its repetition to secure its full effect without danger. When a quick action is required, morphia hypodermically may be preferred; yet it is to be remembered that opium with all its active principles is of more value in the relief of peritonitis than morphia alone. A careful watch should be kept upon all patients treated with large or frequently-repeated doses of opium, that its toxic effects be avoided. Not infrequently symptoms of poisoning have supervened after a sudden relief of pain, necessitating the use of means to keep the patient awake for a number of hours.

Hot embrocations, or poultices applied over large surfaces of the abdomen, give great comfort to the patient, though the very opposite treatment of an ice-bag, occasionally shifted or suspended, is more agreeable in some cases in the inception of the disease.

So soon as a distinct doughy sensation or a more marked fluctuation indicates the development of pus, steps should be undertaken at once to secure its evacuation. In cases of doubt it is best to make a tentative exploration with the needle of the aspirator, a large-sized needle being preferred on account of the liability of occlusion with tissue-shreds or other débris. It is quite surprising how rapidly a case clears up at times after the evacuation of even only a drachm or two of oedematous fluid. More frequently, however, the aspiration must be repeated until a quantity of pus is secured and the abscess completely discharged.

An abscess of more superficial situation, of larger size, or of continuous formation is best relieved by free incision. As to the time of the operation, the old rule, ubi pus ibi incisio, holds good here as elsewhere. An early evacuation of the products of inflammation prevents the supreme danger of perforative peritonitis or the formation of burrowing sinuses, fistulæ, amyloid degeneration, and marasmus.

Indurated tumors are sometimes made to soften under the long-continued use of cataplasms, and chronic thickenings of the walls of the intestine are relieved by general tonics, mild laxatives, mineral waters, and gentle frictions with iodine or mercurial ointments.

Perforative peritonitis calls for opium in maximum doses as a means of facilitating possible agglutinations or encapsulations, and a forlorn hope is offered in an early laparotomy, which the bolder surgeons are now undertaking in the equally desperate cases of perforation by gall- or kidney-stones, etc.

Under no circumstances should a patient affected with typhlitis leave the bed until the last trace of inflammation has subsided, as in no disease is there greater liability to recurrence or relapse.