PubMed Health⌕ Search

Biomedical subjects

L E Hann

Publications and source records attributed to L E Hann.

At least 37 records · Page 2Linked to original sources

Laparoscopic sonography of peripancreatic tumors: preliminary experience.

OBJECTIVE: This study was performed to evaluate the use of laparoscopic sonography in patients with suspected peripancreatic tumors and to assess the impact of laparoscopic sonography on patient management. SUBJECTS AND METHODS: In a prospective study, 24 patients with suspected pancreatic malignancy underwent CT, laparoscopy, and laparoscopic sonography. The pancreas, peripancreatic vasculature, liver, and porta hepatis were evaluated in each patient. Metastases (hepatic, peritoneal, or nodal), extrapancreatic extension of tumor, or vascular encasement was considered evidence of unresectable disease. Histopathology was the standard of reference; unresectable disease was confirmed by biopsy. At the completion of the laparoscopic sonography, each examination was scored according to impact analysis categories that had been prospectively established. RESULTS: Peripancreatic vasculature was adequately shown by laparoscopic sonography in 22 patients (92%), of whom 12 patients had histopathologic evidence of vascular encasement. All 12 cases of vascular encasement were revealed by laparoscopic sonography, and 10 of 12 cases of vascular encasement were revealed by CT. Liver lesions were seen in eight patients (33%). One hemangioma was shown solely by laparoscopic sonography; the other seven liver lesions were revealed by CT, laparoscopy, or both. In six patients (25%), laparoscopic sonography was used to guide biopsy of lesions that were not seen by laparoscopy. Impact analysis showed that laparoscopic sonography provided additional information in eight patients (33%) and altered management in four patients (17%). Of those patients for whom laparoscopic sonography altered management, three patients underwent successful resection after laparoscopic sonography two of these patients had suspected vascular encasement on CT but laparoscopic sonography revealed normal vessels, and the third patient had CT evidence of a liver lesion that was shown to be a cyst on laparoscopic sonography. A fourth patient was spared laparotomy when laparoscopic sonography revealed unsuspected vascular encasement. CONCLUSION: Preliminary experience suggests that laparoscopic sonography may aid diagnosis and alter management in patients with suspected pancreatic neoplasms.

Adenocarcinoma↗

Portal vein evaluation with US: comparison to angiography combined with CT arterial portography.

PURPOSE: To compare ultrasound (US) to angiography combined with computed tomography during arterial portography (CTAP) in the preoperative evaluation of the portal vein. MATERIALS AND METHODS: Sixty-three consecutive patients being considered for hepatic resection underwent color and spectral Doppler US and angiography with CTAP before surgery. The main, right, and left portal veins were evaluated separately. A total of 187 veins were assessed for encasement, occlusion, or thrombosis. RESULTS: At surgery, 41 portal veins were abnormal. US allowed detection of 38 of 41 (93%) involved portal veins with 93% sensitivity, 99% specificity, 97% positive predictive value, and 98% negative predictive value. Angiography with CTAP allowed diagnosis of 37 of 41 (90%) involved portal veins with 90% sensitivity, 99% specificity, 95% positive predictive value, and 97% negative predictive value. CONCLUSION: US is comparable to angiography combined with CTAP in evaluation of the portal vein.

Constriction, Pathologic↗

Hepatic lobar atrophy: association with ipsilateral portal vein obstruction.

OBJECTIVE: This study was performed to evaluate the association between hepatic lobar atrophy, bile duct obstruction, and portal vein obstruction. MATERIALS AND METHODS: Thirty cases of hepatic lobar atrophy identified on angiography with CT during arterial portography from August 1992 to March 1995 were retrospectively reviewed by two independent observers. Cases were evaluated for vascular patency and bile duct obstruction. Malignant diagnoses were present in 28 of 30 patients. RESULTS: Twenty-two patients (73%) had atrophy in the left lobe and eight patients (27%) had right lobar atrophy. Portal vein obstruction was unilateral and confined to the atrophic lobe in 26 patients (87%). In contrast, bile duct obstruction was bilateral in 23 patients (77%) and in only four patients (13%) was it isolated to the atrophic lobe. The correlation between atrophy and portal vein obstruction was significant, with 90% sensitivity, 97% specificity, and 96% positive predictive value (p < .00001). For the correlation between atrophy and biliary obstruction, the sensitivity of angiography with CT during arterial portography was 90%, specificity was 23%, and positive predictive value was 54% (p = .17). CONCLUSION: Hepatic lobar atrophy usually occurs in the setting of combined biliary and portal vein obstruction. A significant correlation exists between hepatic lobar atrophy and ipsilateral portal vein obstruction.

Adult↗

Malignant hepatic hilar tumors: can ultrasonography be used as an alternative to angiography with CT arterial portography for determination of resectability?

Nineteen consecutive patients with malignant hilar obstruction were imaged with angiography, CT portography, and ultrasonography with color and spectral Doppler technique; all had surgical pathologic correlation. At surgery, 12 of 19 patients (63%) were found to have portal vein involvement; 15 of 19 (79%) had parenchymal invasion; and 11 of 19 (58%) had lobar atrophy. Level of biliary obstruction was determined in seven of 19 patients (37%) without drainage catheters. No difference was found between ultrasonography and angiography with CT portography for diagnosis of atrophy, level of bile duct obstruction, hepatic involvement, or venous invasion. Extrahepatic metastases in nine of 19 patients (47%) were poorly predicted by both CT portography and ultrasonography.

Adult↗

mRNAs containing the unstructured 5' leader sequence of alfalfa mosaic virus RNA 4 translate inefficiently in lysates from poliovirus-infected HeLa cells.

Poliovirus infection is accompanied by translational control that precludes translation of 5'-capped mRNAs and facilitates translation of the uncapped poliovirus RNA by an internal initiation mechanism. Previous reports have suggested that the capped alfalfa mosaic virus coat protein mRNA (AIMV CP RNA), which contains an unstructured 5' leader sequence, is unusual in being functionally active in extracts prepared from poliovirus-infected HeLa cells (PI-extracts). To identify the cis-acting nucleotide elements permitting selective AIMV CP expression, we tested capped mRNAs containing structured or unstructured 5' leader sequences in addition to an mRNA containing the poliovirus internal ribosome entry site (IRES). Translations were performed with PI-extracts and extracts prepared from mock-infected HeLa cells (MI-extracts). A number of control criteria demonstrated that the HeLa cells were infected by poliovirus and that the extracts were translationally active. The data strongly indicate that translation of RNAs lacking an internal ribosome entry site, including AIMV CP RNA, was severely compromised in PI-extracts, and we find no evidence that the unstructured AIMV CP RNA 5' leader sequence acts in cis to bypass the poliovirus translational control. Nevertheless, cotranslation assays in the MI-extracts demonstrate that mRNAs containing the unstructured AIMV CP RNA 5' untranslated region have a competitive advantage over those containing the rabbit alpha-globin 5' leader. Previous reports of AIMV CP RNA translation in PI-extracts likely describe inefficient expression that can be explained by residual cap-dependent initiation events, where AIMV CP RNA translation is competitive because of a diminished quantitative requirement for initiation factors.

Alfalfa mosaic virus↗

Stereotaxic core biopsy of breast carcinoma: accuracy at predicting invasion.

PURPOSE: To assess the accuracy with which stereotaxic core biopsy of breast carcinoma predicts the presence of invasion. MATERIALS AND METHODS: Stereotaxic core biopsy was performed in 63 breast carcinomas in 59 patients in the prone position. All patients subsequently underwent surgery. Histopathologic results of stereotaxic core biopsy and surgery were correlated. RESULTS: Results of stereotaxic core biopsy and surgery were concordant in 58 (92%) of the 63 cases, yielding invasive carcinoma in 46 cases and ductal carcinoma in situ (DCIS) in 12 cases. Results were discordant in five cases (8%), including three cases for which stereotaxic core biopsy results indicated DCIS but surgery yielded invasive ductal carcinoma. The positive predictive value of stereotaxic core biopsy for the presence of invasion was 98% (47 of 48 cases) and the negative predictive value was 80% (12 of 15 cases). CONCLUSION: Stereotaxic core biopsy of breast carcinoma can help confirm invasion with high accuracy but cannot reliably indicate the absence of tumor invasion when only DCIS is found.

Biopsy, Needle↗

Impact of stereotaxic core breast biopsy on cost of diagnosis.

PURPOSE: To determine the frequency with which stereotaxic core biopsy of the breast obviated diagnostic surgical biopsy and to estimate the savings in cost of diagnosis with this procedure. MATERIALS AND METHODS: Stereotaxic core biopsy of 182 nonpalpable, mammographically evident lesions was performed, and data from clinical follow-up were obtained. Savings in cost were assessed by using national Medicare reimbursement data and a relative value system based on national physician reviews (Relative Values for Physicians [RVP]). RESULTS: Stereotaxic core biopsy replaced a surgical procedure in 140 of 182 patients. The mean adjusted direct savings in cost per stereotaxic core biopsy were $893 (Medicare) or $1,491 (RVP). Use of stereotaxic core biopsy decreased the cost of diagnosis by 52% (RVP) or 55% (Medicare). CONCLUSION: Stereotaxic core biopsy obviated surgical biopsy for most nonpalpable lesions sampled, resulting in a greater than 50% reduction in biopsy costs. If these results were generalizable to the national level, annual savings would approach $200 million.

Biopsy, Needle↗

Recurrent carcinoma after breast conservation: diagnosis with stereotaxic core biopsy.

PURPOSE: To evaluate the utility of stereotaxic core biopsy (SCB) in diagnosing recurrent carcinoma after breast-conserving therapy (BCT). MATERIALS AND METHODS: Of 316 patients evaluated with SCB, 17 (5%) had nonpalpable lesions in breasts previously treated with BCT. Surgical correlation was obtained in 14 patients. SCBs were performed with digital stereotaxic equipment, with patients prone. RESULTS: Carcinoma detected at SCB in 11 (79%) of 14 patients included infiltrating ductal carcinoma (IFDC) in five, ductal carcinoma in situ (DCIS) in five, and infiltrating lobular carcinoma (ILC) in one. Surgical histopathologic findings agreed with core biopsy findings in 10 of these patients. In one patient with two SCB-proved foci of IFDC, one IFDC was identified at mastectomy. In two (14%) patients, SCB revealed atypical ductal hyperplasia; however, DCIS was found at surgical biopsy. In one patient, the SCB finding of fat necrosis was confirmed at surgical biopsy. CONCLUSION: These data suggest that SCB may be useful in diagnosing recurrent carcinoma in the conservatively treated breast.

Biopsy↗

Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of carcinoma found at surgical biopsy of lesions identified as atypical ductal hyperplasia by stereotaxic core breast biopsy. SUBJECTS AND METHODS: Stereotaxic core biopsies of 264 mammographically evident lesions were done with the patients lying prone on a dedicated stereotaxic table, with an automated gun and a 14-gauge needle. Atypical ductal hyperplasia was identified in 25 (9%) of 264 lesions, including four (3%) of 159 masses and 21 (20%) of 105 lesions evident as calcifications. Surgical biopsy was recommended in all 25 of these cases and was performed in 21. Results of stereotaxic core biopsy and surgery in these 21 cases were reviewed and correlated. RESULTS: Of 21 cases identified as atypical ductal hyperplasia at stereotaxic core biopsy that were subsequently evaluated with surgical biopsy, histopathologic analysis of the surgical specimen yielded benign histologic findings without atypia in four (19%), atypical ductal hyperplasia in six (29%), and carcinoma in 11 (52%). Of the 11 carcinomas, histologic findings showed ductal carcinoma in situ in eight (73%) and invasive ductal carcinoma in three (27%). CONCLUSION: The finding of atypical ductal hyperplasia at stereotaxic core breast biopsy is an indication for surgical biopsy because of the high prevalence of ductal carcinoma in these lesions.

Biopsy, Needle↗

Mammography immediately after stereotaxic breast biopsy: is it necessary?

OBJECTIVE: The purpose of this study was to determine whether mammography immediately after stereotaxic core breast biopsy should be performed routinely to diagnose hematoma, to confirm the sampling site, and to establish a new baseline for future mammograms. MATERIALS AND METHODS: Stereotaxic core biopsies of 113 mammographically indeterminate or suspicious lesions were performed by use of a dedicated stereotaxic table with digital imaging, a 14-gauge needle, and an automated gun. The indication for biopsy was a mass with or without calcifications in 59 cases (52%) and calcifications without a mass in 54 cases (48%). The number of core biopsies per case ranged from one to 16 (mean = six). Craniocaudal and mediolateral oblique mammograms of the sampled breast were obtained immediately after the biopsies and were compared with prebiopsy mammograms. In cases with microcalcifications, the mammograms also were compared with specimen radiographs. RESULTS: Mammograms obtained immediately after the procedure showed changes related to the biopsy in 86 cases (76%). These findings included decreased lesion size in 11 (10%), air at the biopsy site in 47 (42%), and hematoma, manifested as poorly defined increased density at the biopsy site, in 58 (51%). One hematoma was clinically significant, but the remaining 57 were clinically occult. When core biopsies were performed for calcifications, the postprocedural mammograms showed a decrease in the number of calcifications in 26 (48%) of 54 cases, but specimen radiographs showed calcium in 50 (93%) of 54 cases. Four lesions (three masses and one cluster of microcalcifications) disappeared after biopsy. In three cases, hematomas obscured residual calcifications at the biopsy site. CONCLUSION: Mammography immediately after core biopsy is not necessary for the diagnosis of procedure-related hematoma and is inferior to specimen radiography for verifying that calcifications have been sampled. Postprocedural mammograms also may be suboptimal for the establishment of a new baseline because of the frequent finding of hematoma.

Adult↗

Stereotaxic core biopsy of impalpable spiculated breast masses.

OBJECTIVE: The role of stereotaxic core biopsy in evaluating mammographically detected lesions that have a high probability of being malignant is still debated. This study was undertaken to assess the use of stereotaxic core biopsy in evaluating spiculated masses, by determining the frequency with which core biopsy reduced the number of surgical procedures performed in the management of these highly suspicious lesions. MATERIALS AND METHODS: Forty-three impalpable spiculated breast masses in 43 patients were sampled with stereotaxic core biopsy. All patients underwent surgery. Patient charts were reviewed to determine the histopathologic findings at stereotaxic core biopsy and at surgery, and the number and type of surgeries performed. RESULTS: Invasive carcinoma was identified at stereotaxic core biopsy in 40 (93%) of 43 patients. Therapeutic surgical procedures were lumpectomy in 28 patients (22 with axillary dissection) and mastectomy in 12. The presence of tumor at the lumpectomy margins led to subsequent mastectomy in one case. One lesion yielded atypical ductal hyperplasia at core biopsy; surgical biopsy revealed ductal carcinoma in situ. Surgical biopsy was recommended in two lesions yielding benign histologies at core biopsy and revealed invasive ductal carcinoma in one. Thirty-three (77%) of 43 patients had the number of surgical procedures reduced by stereotaxic core biopsy; these were patients with carcinoma diagnosed at core biopsy who underwent one-stage lumpectomy with axillary lymph node dissection or mastectomy. CONCLUSION: Stereotaxic core biopsy reduced the number of surgical procedures in most women with impalpable spiculated breast masses. These data suggest that stereotaxic core biopsy is a valuable diagnostic technique for assessing these lesions, which are likely to represent carcinoma.

Adult↗

Radiography of microcalcifications in stereotaxic mammary core biopsy specimens.

PURPOSE: To describe the technique of specimen radiography in stereotaxically guided core biopsies and evaluate its role in detection and diagnosis of microcalcifications in breast tissue. MATERIALS AND METHODS: Specimens from 361 stereotaxic breast core biopsies of 72 nonpalpable lesions with mammographic evidence of microcalcifications were obtained from 65 patients. Specimens were placed in saline on microscope slides and radiographed. RESULTS: Microcalcifications were detected radiographically in 146 of 361 (40%) cores. If calcifications were present on specimen radiographs, histologic detection of these calcifications was made in 114 of 146 (78%) specimens, and diagnosis was made in 118 of 146 (81%). If calcifications were not present on specimen radiographs, histologic detection was obtained in 27 of 215 (13%) specimens and specific diagnosis in 81 of 215 (38%). CONCLUSION: Specimen radiography should be routinely performed in stereotaxic core biopsies of breast microcalcifications to ensure appropriate tissue has been obtained and to direct pathologic diagnosis of the tissue specimens.

Adult↗

Stereotaxic 14-gauge breast biopsy: how many core biopsy specimens are needed?

PURPOSE: To determine the optimum number of specimens to obtain at stereotaxic core breast biopsy. MATERIALS AND METHODS: Stereotaxic biopsies were performed in 145 mammographically evident lesions by using a dedicated table with patients in the prone position. Samples were obtained with an automated gun and a 14-gauge needle. Indications for biopsy were calcifications (n = 53) and masses (n = 92). Three to 11 (mean, 5.4) core biopsy specimens were obtained per lesion and were analyzed separately. RESULTS: Diagnostic material was obtained in the first specimen in 102 (70%) of the 145 lesions. Obtaining two, three, four, five, and six core specimens yielded a diagnosis in 117 (81%), 129 (89%), 132 (91%), 137 (94%), and 140 (97%) of the 145 lesions, respectively. Obtaining five specimens yielded a diagnosis in 46 (87%) of the 53 calcifications and 91 (99%) of the 92 masses. Obtaining six specimens resulted in a diagnosis in 49 (92%) lesions evident as calcifications but did not improve the yield on masses. CONCLUSION: Stereotaxic 14-gauge core biopsy achieved a 99% diagnostic yield with five specimens for masses. Additional specimens may be necessary to diagnose some calcified lesions.

Biopsy, Needle↗

Transrectal ultrasonography and operative selection for early carcinoma of the rectum.

BACKGROUND: Transrectal ultrasonography (TRUS) supplements clinical evaluation of early carcinoma of the rectum in selecting patients for local operative therapy, such as transanal excision (TAE). STUDY DESIGN: This study was done to evaluate the accuracy of ultrasonographic staging of tumor depth (T stage) in patients with suspected early carcinoma of the rectum, to compare ultrasonographic with clinical T-staging accuracies within this patient group, to determine if any specific tumor characteristics (configuration, size, location) predispose toward ultrasonographic T-staging inaccuracy, and to examine the role of TRUS in operative selection for patients with early carcinoma of the rectum. RESULTS: Between April 1990 and December 1992, 62 patients with primary carcinoma of the rectum underwent ultrasonographic staging (uT), whereby three uT4, 27 uT3, 24 uT2 and eight uT1 carcinomas were identified. Of the 32 patients with suspected intramural (uT1 or uT2) disease, 27 underwent prompt operative excision or resection at our institution, allowing comparative histopathologic staging. In this highly selected patient subset, uT1 staging was correct in all instances; uT2 staging was incorrect in 45 percent of instances, with 30 percent having unpredicted transmural penetration. Ultrasonographic and clinical staging accuracies were quantitatively similar, and no tumor characteristics were consistently associated with ultrasonographic imprecision. CONCLUSIONS: Among patients with clinically suspected early carcinoma of the rectum, the decision to perform TAE is supported by ultrasonographic T1 staging. By contrast, the decision to perform TAE cannot be based solely on ultrasonographic T2 staging, because of the possibility for transmural penetration of tumor.

Adult↗

Endocrine, neural, and immune control of secretory component output by lacrimal gland acinar cells.

Androgens regulate the synthesis and secretion of secretory component (SC), the IgA antibody receptor, by acinar cells from the lacrimal gland. However, this hormone action may be susceptible to significant modification by other agents from the endocrine, nervous, or immune systems. To investigate the nature of this neuroimmunoendocrine interaction, the present study examined the impact of hormones, neurotransmitters, and lymphokines on basal and androgen-induced SC production by lacrimal gland acinar cells in vitro. Our results demonstrated that vasoactive intestinal peptide, the beta-adrenergic agonist, isoproterenol, PGE2, IL-1 alpha, IL-1 beta, and TNF-alpha significantly increased media SC levels in control or androgen-containing cell cultures. In contrast, the cholinergic agonist, carbachol, significantly decreased cellular SC output. These effects may be mediated through the agents' known capacity to alter intracellular cAMP levels. In support of this hypothesis, exposure of acinar cells to stimulators or analogues of cAMP resulted in a significant enhancement of SC production. Thus, these findings indicate that SC output in lacrimal tissue may be modulated by interactions between the endocrine, nervous and immune systems.

1-Methyl-3-isobutylxanthine↗

Influence of culture conditions on the androgen control of secretory component production by acinar cells from the rat lacrimal gland.

Research has shown that androgens regulate the production of secretory component (SC), the IgA antibody receptor, by lacrimal gland acinar cells in vivo. This study was designed to establish an optimal culture system to permit analysis of this endocrine-acinar cell interrelationship in vitro. Acinar cells were isolated from male rat lacrimal glands and cultured on Matrigel (Collaborative Research, Bedford, MA) in serum-free Dulbecco's modified Eagle's medium (DMEM)/Ham's F12 media that contained a variety of supplements. Under these conditions, acinar cells responded to dihydrotestosterone (DHT) exposure with a significant increase in SC output. Replacement of the DMEM/Ham's F12 media base with either Modified Eagle's Medium (MEM) or low-calcium MEM inhibited this hormone response and dramatically reduced cell recovery after 4 days of culture. Similarly, decreased concentrations or deletions of selected media supplements, including insulin, which binds to acinar cells, and dexamethasone, led to a significant diminution in the extent of androgen action, as well as to a decline in cell maintenance. In contrast, removal of high-density lipoprotein from culture media or the addition of fetal bovine serum (FBS) or cholera toxin significantly enhanced basal and DHT-associated SC production by acinar cells. With regard to extracellular matrices, Matrigel proved to be superior to collagen type I, laminin, fibronectin, or the Primaria (Falcon, Oxnard, CA) plastic surface in providing support for acinar cell association or hormone-related function. In summary, our results show that the media formulation, supplement profile, and extracellular matrix composition are important for maximal expression of androgen-induced effects by lacrimal gland acinar cells in vitro.

Androgens↗

Androgen regulation of secretory component synthesis by lacrimal gland acinar cells in vitro.

This study sought to determine whether androgens directly stimulate the production of secretory component (SC) by acinar cells from the rat lacrimal gland. Homogeneous populations of acrinar cells were isolated from lacrimal tissues by serial enzymatic digestion and Ficoll gradient centrifugation and then cultured on reconstituted basement membranes in supplemented, serum-free medium. Acinar cell exposure in vitro to dihydrotestosterone (DHT) resulted in a significant increase in cellular SC output. This hormone action was dose dependent and androgen specific. Testosterone, but not 17 beta-estradiol, progesterone, dexamethasone, or aldosterone, also induced a considerable elevation in acinar cell SC production. The effect of testosterone may not require intracellular enzymatic conversion to DHT. The impact of androgens on SC output was associated with enhanced cellular synthesis and secretion and did not involve variations in acinar cell viability or density. Moreover, the SC response to DHT occurred irrespective of whether lacrimal gland acinar cells were obtained from young adult male or female rats. In contrast, the androgen-related rise in SC production was significantly reduced in acinar cells isolated from tissue of orchiectomized and hypophysectomized rats. In summary, these findings demonstrate that androgens directly increase the synthesis of SC by lacrimal gland acinar cells in vitro. This effect, however, may be significantly altered by prior changes in the endocrine environment of acinar cells in vivo.

Aldosterone↗

Age- and gender-related influence on the lacrimal gland and tears.

Previous research has demonstrated that distinct, gender-related differences exist in lacrimal glands in a variety of adult species. The objective of the current investigation was to examine whether this influence of gender extends throughout development and aging. Towards that end, morphological parameters of the lacrimal gland, as well as the volume, protein and IgG content of tears, were measured in male and female infant, preweanling, pubertal, adult, mid-life and senescent rats. Our results showed that dramatic, age-related variations occurred in the weight and morphological appearance of the lacrimal gland. Moreover, the magnitude of structural changes was dependent upon gender. Acinar area was significantly greater in lacrimal tissue of males, as compared to females, at all ages except pre-weanling; this sexual dimorphism was most evident in senescent rats. In contrast, acinar density in lacrimal glands of females was higher than, or equal to, that of males throughout development and aging. With regard to tears, pronounced increases were evident in tear volume, protein and IgG content from the pre-weanling stage to adulthood. After this time, these tear indices tended either to plateau or rise slightly until senescence. Gender had little or no impact of the volume of, or protein and IgG level in, tears. Of interest, the IgG/protein ratio in tears was 49- to 105-fold less than that found in lacrimal tissue, indicating that IgG moves down a gradient from the lacrimal gland to tears. Overall, our findings demonstrate that gender has a significant influence on lacrimal gland structure during development and aging. However, this impact is limited with respect to tear volume and protein content.

Aging↗