Biomedical subjects

J S Lin

Publications and source records attributed to J S Lin.

At least 127 records · Page 7Linked to original sources

PubMed1995

The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.

Although there are reports that the addition of a beta-lactamase inhibitor to ampicillin or amoxicillin greatly improves their in vitro activity against M. tuberculosis, there are no written reports about the antituberculosis effects of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis. In this report, we have determined the minimal inhibitory concentrations (MIC) of 5 cephalosporins with or without combination with beta-lactamase inhibitor against M. tuberculosis strains isolated from patients before antituberculosis treatment and checked the production of beta-lactamase by bacteria before this procedure. Four strains of M. tuberculosis were contaminated during the experiment, and all the other 16 strains hydrolyzed the nitrocefin disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400 micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600 micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After adding the equimolar concentrations of sulbactam, the MICs were reduced to 100-200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400 micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800 micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the antituberculosis effect of cephalosporins.

Cefamandole↗

PubMed1995

Allogeneic peripheral blood progenitor cell transplant after bone marrow graft failure: report of a case.

A 31-year-old woman diagnosed with acute myelocytic leukemia received an allogeneic peripheral blood progenitor cell (PBPC) transplant one month after a previous bone marrow graft failed. PBPCs were mobilized with granulocyte-colony-stimulating factor and collected by apheresis. T-cell depletion was not performed and no further chemo- or radiotherapy was given for the second transplant. Engraftment was prompt, with the peripheral blood leukocyte count rising dramatically to 2,400/microL, six days after completion of PBPC transplant. The platelet count reached 36,000/microL on the eighth day and was self-sustained thereafter. Both blood grouping and bone marrow karyotyping confirmed donor origin of the engraftment. At the time of writing, the patient has been disease-free for over 200 days without any complications of acute or chronic graft-versus-host disease.

Adult↗

PubMed1995

[Hemolytic disease of the newborn caused by maternal anti-Di(a): a case report in Taiwan].

The first case of hemolytic disease of the newborn (HDN) possibly caused by anti-Di(a) in a Chinese infant in Taiwan is reported. The mother had two pregnancies before but no history of blood transfusion. Her first male infant was normal, but her second full-term male one developed mild jaundice soon after birth, and the total bilirubin level was 12.1 mg/dL, 18.3 mg/dL, 23.6 mg/dL at 24 hours, 48 hours, and 72 hours of age, respectively. Total bilirubin was 9.1 mg/dL on the eighth day after receiving phototherapy and compatible blood exchange transfusion. The infant recovered uneventfully. The immunohematological study revealed that the mother was group AB, Rh (D)+; Di(a - b+), the father was group O, Rh (D)+; Di(a + b+), the infant boy and his 2-year-old brother were group B, Rh(D)+; Di(a + b+). The direct antiglobulin test (DAT) on the infant red cells was positive (4+ with polyspecific AHG; 4+ with anti-IgG). The maternal serum and infant's eluate from red blood cells showed negative reactions in routine antibody detection tests, but they contained alloantibody reacting against the Di(a+) cells by the manual polybrene test (MP) and indirect antiglobulin test (IAT) in AHG phase. The anti-Di(a) titers in the mother's serum was MP 1:256 and AHG 1:256, and in the infant's eluate was MP 1:128 and AHC 1:64 against Di(a + b+) cells. Based on the above results we conclude that the jaundice in this newborn baby was caused by maternal anti-Di(a) which was most likely induced by previous pregnancy. In conclusion, Diego blood group is a system of high value in anthropology because it accounts for the Mongoloid origin of American Indians, Japanese and Chinese. Anti-Di(a) may cause HDN, as in our case of HDN due to maternal anti-Di(a) in a Chinese infant. But in Europe and America, where practically all people are Di(a - b+) phenotypes, the system seems of no interest in parental studies as well as in blood transfusions. Owing to the Di(a) antigen is of higher incidence in Chinese population, we suggest that the Diego system should be involved in routine compatibility testing or antibody identification problems in parental studies and in blood transfusions in Taiwan.

Blood Group Antigens↗

PubMed1994

Hypothalamo-preoptic histaminergic projections in sleep-wake control in the cat.

Cats were chronically implanted with electrodes for polygraphic recordings and cannulae for intracerebral microinjections in order to study the functional role of histaminergic innervation of the preoptic-anterior hypothalamus in sleep-wake control. alpha-Fluoromethylhistidine (alpha FMH, 50 micrograms in 1 microliter), a specific inhibitor of the histamine-synthesizing enzyme, when injected bilaterally into the preoptic area, where numerous histaminergic fibres and terminal-like structures are present, caused a significant increase in deep slow wave sleep (S2) and paradoxical sleep (PS) and a decrease in wakefulness. In contrast, microinjections of histamine (5 or 30 micrograms in 1 microliter) in the same area dose-relatedly increased wakefulness and decreased both slow wave sleep and paradoxical sleep. The effects of histamine were reduced by pretreatment with mepyramine (1 mg/kg i.p.), a well known histamine H1 receptor antagonist, and were mimicked by a local injection of impromidine (1 microgram in 1 microliter), a potent histamine H2 receptor agonist. Microinjections of mepyramine alone (120 micrograms in 1 microliter) caused an increase in slow wave sleep. These results suggest that preoptic histaminergic innervation is involved in sleep-wake control and that the action might be mediated via both H1 and H2 receptors.

Animals↗

PubMed1994

Factors contributing to the prognostic significance of bone marrow involvement in childhood non-Hodgkin lymphoma.

To evaluate the clinical characteristics and treatment outcome of childhood non-Hodgkin lymphoma (NHL) cases with bone marrow involvement, we studied 13 lymphoblastic, 15 small noncleaved cell, and 8 large cell cases with tumor cells in their marrow. They represented 16%, 11%, and 9% of consecutive NHL cases with these respective histologic subtypes. The treatment outcome differed significantly according to histologic subtype--the 5-year event-free survivals (EFS +/- SE) for large cell NHL, small non-cleaved cell NHL, and lymphoblastic NHL cases were 11 +/- 8%, 40 +/- 20%, and 62 +/- 15%, respectively. Increased serum lactate dehydrogenase (LDH) levels (> 500 U/L) were associated with a poorer EFS (5-year EFS, 0% vs. 50 +/- 10%; P < 0.001). Children < or = 5 years of age had a poorer EFS survival than older children (5-year EFS, 14 +/- 9% vs. 44 +/- 10%; P = 0.03). The degree of bone marrow involvement (< 5% vs. > or = 5%) and race were not significantly associated with treatment outcome. Although intensive chemotherapy has substantially improved survival for patients with advanced stage lymphoblastic or small noncleaved cell lymphoma, patients with large cell NHL and associated marrow involvement continue to have a dismal outcome and require novel or more intensive therapy.

Adolescent↗

PubMed1994

An assessment of immunoreactive epidermal growth factor in urine of patients with urological diseases.

To examine the excretion of urinary epidermal growth factor (EGF) in urological diseases and the relationship of EGF urine levels with transitional cell carcinoma (TCC), we measured the concentration of EGF by radioimmunoassay. The series comprised patients with active TCC (n = 52), others in tumor-free status (n = 29) and with non-neoplastic inflammatory diseases (n = 43), and normal controls (n = 50). Urinary EGF values were lower in patients with urological diseases of different etiologies than in normal controls (P < 0.005). Mean EGF levels of patients who had previous bladder tumor resection (n = 21) were not statistically different from normal controls (P = 0.2). For patients with active TCC, EGF urine levels showed a significant inverse relationship to increasing tumor grade (P = 0.02). In addition, subjects who had received nephrectomy for pelvic carcinoma (n = 8) showed significantly lower mean EGF values than those with intact kidneys (n = 21), irrespective of sex (P < 0.05). Immunostaining of EGF on non-neoplastic kidney (n = 9) revealed reactivity in the distal convoluted tubules and thick ascending limbs of Henle. Our results suggest that the kidney is the major source of urinary EGF. Its excretion in urine is decreased in both inflammatory and neoplastic diseases of the urinary tract. EGF may play an important part in the biological activity of TCC. Further study is indicated to investigate the monitoring of EGF urine levels as a marker of recurrence for EGF receptor-positive TCC.

Adult↗

PubMed1994

Thiopurine methyltransferase activity in American white subjects and black subjects.

BACKGROUND: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including 6-mercaptopurine. TPMT exhibits genetic polymorphism in white populations, with 89% of individuals having high TPMT activity, 11% having intermediate activity, and one in 300 having extremely low or absent activity. TPMT activity is inversely correlated with formation of active 6-mercaptopurine metabolites (thioguanine nucleotides), thereby influencing 6-mercaptopurine toxicity and efficacy. METHODS: To investigate ethnic and gender differences in TPMT, we measured erythrocyte TPMT activity in 209 white healthy subjects and 196 black healthy subjects (202 women and 303 men). RESULTS: The black population had lower TPMT activity than the white population (median, 14.4 versus 16.8 units/ml packed erythrocytes; p < 0.001). Maximum likelihood estimation of TPMT activity distribution identified 91.9% and 93.9% with high activity and 7.7% and 6.1% with intermediate activity in the white and black groups, respectively. CONCLUSIONS: These data indicate that TPMT activity is similarly polymorphic in American black subjects and white subjects, although median TPMT activity is approximately 17% lower in black subjects.

Adolescent↗

PubMed1994

Red cells, HLA and platelet antibody formation in patients with multiple transfusions.

Totally 436 Chinese patients having received multiple transfusions of red cells and platelets on more than three occasions were screened for red cell antibodies. Twenty-six (6%) of them were positive. Anti-E, -Mia, and -c were the common alloantibodies. Nine patients were immunized during the period of regular transfusions, with a newly immunized rate of 2% (9/436). Among 436 patients, 387 were screened for HLA antibodies by lymphocytotoxicity test (LCT). The overall positive rate was 35%. Most of the antibodies identified were against the high-frequency HLA antigens in the Chinese population. About 10% of the LCT-positive cases reverted to negative state during the follow-up period. After chloroquine stripping of the target platelets, mixed passive hemagglutination assay was used to detect platelet antibodies other than HLA antibody. Fifty-eight of 161 cases (36%) were positive for platelet antibodies, but half of them disappeared within 1 month. Nineteen of the 58 patients had sepsis and 2 had jaundice. These findings suggested that HLA and platelet antibodies are common among Chinese, though their clinical significance and the role in platelet damage are doubtful.

Antibody Specificity↗

PubMed1994

Effects of chemoimmunotherapy with and without surgery in murine MBT-2 bladder tumor.

Using C3H/He JCr mice bearing the syngeneic MBT-2 bladder tumor, it was found that cyclophosphamide (CYC 100 mg/kg i.p.) treatment, 1 day before and 2 weeks after surgery, followed by postoperative autologous tumor vaccine immunization can be an effective adjuvant anticancer therapy. The short-term exogeneous addition of low dose Il-2 administration to the protocol provided no further benefit. Suppression of tumor growth was observed in a classical Winn assay when splenocytes were obtained on day 23 from mice receiving this effective adjuvant therapy with surgery on day 8. Splenocytes from tumor-bearing mice (TBM) treated with CYC were augmented in terms of their proliferative response to concanavalin A during the first 2 weeks after CYC treatment. Studies using 3-day TBM established that significant suppression of tumor growth and prolonged survivals were dependent upon CYC treatment being combined with tumor vaccine and/or interleukin-2; single agent treatments were ineffective.

Animals↗

PubMed1994

Urinary cytodiagnosis: can it have a different prognostic implication than a diagnostic test?

In order to assess the clinical implications of the cytology of voided urine we analyzed 65 patients among 147 cases of transitional cell carcinoma (TCC) in relation to the cytohistologic correlation and prognostic significance. Urinary cytology detected 42.6% of bladder tumors, 59% of renal pelvic tumors, and 35.3% of ureteral carcinomas. None of the 3 cases of grade-1 upper urinary tract tumors was detected by preoperative urinary cytology. Tumors with positive cytology were associated with epidermal growth factor receptor expression (p = 0.0009) and a higher fraction of tumor proliferation as defined by Ki-67 immunohistochemistry (p = 0.0038). Anaplastic tumor cells in urine correlated fairly well with muscular invasion (p = 0.018) and the DNA aneuploidy of the tumor (p = 0.0038). Tumors with muscular invasion were more likely to be detected by cytologic examination (p = 0.013). In urinary bladder carcinoma (n = 107), patients with positive cytology had a higher incidence of tumor recurrence (p = 0.004), and had an unfavorable prognosis (p = 0.0001) with a median follow-up of 46 months. In Ta-T1 tumors (n = 87), urinary cytology had prognostic value in terms of risk of recurrence (p = 0.0001), and poor patient outcome (p = 0.0001). Our data suggest that urinary cytology can offer important biological information on TCC and may be used as a simple and effective short-term prognostic indicator.

Adult↗

PubMed1994

Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CD30 expression and its relationship to clinical features, immunophenotype, histotype, and outcome in childhood large-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: We reviewed 45 cases of large-cell NHL in children treated at St Jude Children's Research Hospital from 1975 to 1990 for whom there was sufficient tissue to perform immunophenotypic studies. All 45 were screened with a panel of antibodies to detect the presence of CD30 and T-cell and B-cell antigens. Cases were classified according to the National Cancer Institute (NCI) Working Formulation and the Kiel classification system. Clinical features, immunophenotype, pathologic classification, and treatment outcome were compared for CD30+ and CD30- cases. RESULTS: CD30 expression was documented in 18 cases (40%). These 13 boys and five girls had a median age of 13 years at diagnosis. Most (n = 14) had advanced-stage (III and IV) disease. Nodal disease was equally common in CD30+ and CD30- cases, whereas skin involvement was significantly more frequent in CD30+ cases (P = .007). There was no significant association of CD30 expression with histologic subtype according to the NCI Working Formulation, but CD30+ cases were more likely to be anaplastic by the Kiel classification (P < .001). All CD30+ cases had either T-cell or null-cell phenotype, while the majority of CD30- cases were B-cell phenotype (P < .001). Among patients with limited-stage disease, the mean +/- SE estimated 5-year event-free survival (EFS) was 75% +/- 22% for CD30+ cases and 92% +/- 9% for CD30- cases (P = .10); estimates for advanced-stage disease were 57% +/- 17% and 29% +/- 17%, respectively (P = .096). For patients with advanced-stage disease, CD30 expression was associated with a significantly better overall 5-year survival probability (84% +/- 12% v 27% +/- 16%, P = .0016). CONCLUSION: CD30 is frequently expressed in pediatric large-cell NHL and is significantly associated with T-cell or null-cell phenotype, anaplastic morphology, skin involvement, and better overall survival among advanced-stage patients.

Adolescent↗

PubMed1994

The change of penile blood thromboxane B2 and prostacyclin after intracavernous injection of vasoactive drugs for the treatment of arteriogenic impotence.

Penile hypercoagulability during erection may predispose to aging vascular changes and, eventually, arteriogenic impotence. The relationship of penile blood thromboxane B2 and 6-keto-prostaglandin F1 alpha in both psychogenically and arteriogenically impotent patients after intracavernosal treatment with papaverine plus phentolamine or prostaglandin E1 was evaluated. No significant change in penile blood thromboxane B2 was observed with treatment of these vasoactive drugs. On the other hand, penile blood 6-keto-prostaglandin F1 alpha was significantly increased with the injection of 30 mg of papaverine plus 0.5 mg of phentolamine, and of 20 micrograms prostaglandin E1. Furthermore, the prostacyclin-to-thromboxane A2 ratio for the patient who received papaverine plus phentolamine was significantly lower than that for the same individual receiving prostaglandin E1. Our preliminary findings suggest that penile blood prostacyclin may participate in the pathogenesis of arteriogenic impotence and priapism.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Large cell non-Hodgkin lymphoma of childhood: clinical characteristics and outcome.

Less is known about the clinical features and treatment outcome in pediatric large cell non-Hodgkin lymphoma (NHL) than the lymphoblastic and small noncleaved cell subtypes of NHL. To characterize presenting features and assess possible risk factors associated with this diagnosis, we analyzed data for 91 patients treated on a succession of multiagent regimens from 1975 to 1990. Five-year event-free survival (EFS) (+/- SE) was related to disease extent (St Jude system): stage I (n = 24), 95% +/- 5%; stage II (n = 20), 84% +/- 9%; stage III (n = 38), 50% +/- 10%; and stage IV (n = 9), 22% +/- 11%. Advanced stage disease, age < or = 5 years and serum LDH > 500 U/l were associated with poorer EFS in the univariate model (p < 0.001, 0.005, and 0.002, respectively). In the multivariate model, advanced stage and age retained prognostic significance (p = 0.001 and 0.02, respectively), but LDH did not. Among limited stage cases, age < or = 5 years was the only adverse risk feature (p = 0.016); treatment era (pre- vs. post-1979) was the only significant feature in patients with advanced disease (p = 0.004). Intrathoracic primaries were associated with a better outcome than other sites among the 38 stage III patients (p = 0.005). Only one of eight patients with bone marrow disease remains failure-free. The excellent results for limited stage pediatric large cell NHL permit consideration of treatment modifications to decrease toxicity; for cases with advanced disease, especially those with bone marrow involvement, novel therapeutic approaches are clearly needed.

Adolescent↗

PubMed1993

Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.

Animals↗

PubMed1993

Automatic lung nodule detection using profile matching and back-propagation neural network techniques.

The potential advantages of using digital techniques instead of film-based radiography have been discussed extensively for the past 10 years. A major future application of digital techniques is computer-assisted diagnosis: the use of computer techniques to assist the radiologist in the diagnostic process. One aspect of this assistance is computer-assisted detection. The detection of small lung nodule has been recognized as a clinically difficult task for many years. Most of the literature has indicated that the rate for finding lung nodules (size range from 3 mm to 15 mm) is only approximately 65%, in those cases in which the undetected nodules could be found retrospectively. In recent published research, image processing techniques, such as thresholding and morphological analysis, have been used to enhance true-positive detection. However, these methods still produce many false-positive detections. We have been investigating the use of neural networks to distinguish true-positives nodule detections among those areas of interest that are generated from a signal enhanced image. The initial results show that the trained neural networks program can increase true-positive detections and moderately reduce the number of false-positive detections. The program reported here can perform three modes of lung nodule detection: thresholding, profile matching analysis, and neural network. This program is fully automatic and has been implemented in a DEC 5000/200 (Digital Equipment Corp, Maynard, MA) workstation. The total processing time for all three methods is less than 35 seconds. In this report, key image processing techniques and neural network for the lung nodule detection are described and the results of this initial study are reported.

Algorithms↗

PubMed1993

Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans.

Debrisoquin hydroxylase (CYP2D6) is a cytochrome P450 enzyme that catalyzes the metabolism of > 30 commonly prescribed medications. Deficiency in CYP2D6 activity, inherited as an autosomal recessive trait, was found to be significantly less common in American blacks (1.9%) than whites (7.7%). To determine the genetic basis for this difference, inactivating CYP2D6 mutations were assessed by allele-specific PCR amplification and RFLP analyses of genomic DNA from 126 unrelated whites and 127 unrelated blacks. Blacks had a twofold lower frequency (8.5 versus 23%, P = 0.001) of the CYP2D6(B) mutation (point mutation at intron 3/exon 4 splice site), while complete deletion of the CYP2D6 gene (5.5% blacks, 2.4% whites), and the CYP2D6(A) mutation (single nucleotide deletion in exon 5; 0.24% blacks, 1.4% whites) were not different between the two groups. The prevalence of heterozygous genotypes was significantly lower in blacks (25 versus 42% of extensive metabolizers, P = 0.009), consistent with the observed prevalence of the deficient trait in blacks and whites. We conclude that the same CYP2D6 mutations lead to a loss of functional expression in blacks and whites, but American blacks have a lower prevalence of the deficient trait due to a lower frequency of the CYP2D6(B) mutation. This could explain racial differences in drug effects and disease risk.

Base Sequence↗

PubMed1993

Application of artificial neural networks for reduction of false-positive detections in digital chest radiographs.

A methodology based on the fuzzy set theory and the convolution neural network (CNN) architecture is proposed to tackle the problem of reducing false-positive rate in automatic lung nodule detection. The CNN which simulates human visual mechanism was trained by a supervised back-propagation algorithm based on fuzzy membership functions. The training and testing database consists of image blocks (each 32 x 32 pixels) of suspected lung nodule areas (nodule candidates) which were generated from our pre-scanning program [1]. A linguistic label was assigned to each nodule candidate of the training set, then the label was converted to a membership value through a pre-defined membership function and used as teaching signal (desired outputs) during the network learning. Before the nodule candidate was fed to the network input, it was pre-processed to reduce the complex background noise and the contrast discrepancy resulted from film development. During the network testing phase, a defuzzification process was applied to decipher the trained network's output triggered by the nodule candidate in the testing set. Finally, a Receiver Operating Characteristic (ROC) analysis was used to evaluate the CNN's performance based on the defuzzified output of the testing database. Preliminary results showed an average Az (the performance index) of 0.84 which is equivalent to 0.80 true-positive detection (sensitivity) with an average 2-3 false-positive detections per chest image.

Computer Simulation↗

PubMed1993

Adult type squamous papillomatosis of larynx with extension to trachea and bronchial tree: a report of two cases.

We describe 2 rare cases of adult type squamous papillomatosis of larynx with spread to the trachea and bronchial tree that occurred at the age of 72 and 42, respectively. They were treated with laser therapy for laryngeal and tracheal lesions; the first case also received surgical resection. However, due to the extent of papilloma involvement, the outcomes were completely different between both. The first patient had all lesions successfully removed by combined surgical resection and laser photoresection, and the patient remained asymptomatic up to 7 years after the operation. The second patient, however, had been bothered by recurrent tumors with associated repeated secondary infections, despite treatment, for 6 years and 3 months before his death.

Adult↗