Biomedical subjects

J Yuen

Publications and source records attributed to J Yuen.

At least 55 records · Page 3Linked to original sources

PubMed1996

Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy--long-term follow-up of a Swedish cohort.

We analyzed cancer incidence and mortality in a cohort of 22,597 Swedish women who were prescribed replacement hormones. After 13 years of follow-up in national registries, 2,330 incident cancer cases and 848 cancer deaths were observed. Overall, our results were reassuring since incidence rate ratios (SIRs) for 16 cancer sites and mortality ratios (SMRs) for all 10 examined sites were at, or lower than, unity. However, we found that exposure to an estrogen-progestin combined brand was associated with an increasing relative risk of breast cancer with follow-up time, the SIR reaching 1.4 (95% CI 1.1-1.8) after 10 years of follow-up. The relative risk of endometrial cancer was substantially increased, with the highest SIR of 5.0 (95% CI 1.6-5.9) in women prescribed estrogens alone, whereas those given an estrogen-progestin combination showed no elevation in risk. The risk estimates for liver and biliary tract cancers and for colon cancer were reduced by about 40%, notably in women prescribed the estradiol-progestin compound. Further detailed analyses revealed no evidence of adverse or protective effects on the risk of ovarian, uterine cervical, vulvar/vaginal, rectal, pancreatic, renal, lung, thyroid and other endocrine cancers, brain tumors, malignant melanoma or other skin cancers. Hormone replacement therapy was not associated with an increase in mortality for any cancer site, at this time of follow-up. For breast and endometrial cancers, SMRs were below baseline but tended to increase with follow-up time. We conclude that hormone replacement increases the endometrial-cancer risk after unopposed estrogens and the breast-cancer risk-notably after estrogen-progestin combined therapy-and tentatively suggest that it exerts a protective effect against colon and liver cancer risks.

Aged↗

PubMed1996

Risk of pancreatic and periampullar cancer following cholecystectomy: a population-based cohort study.

An increased risk of pancreatic cancer following cholecystectomy has been reported in some studies but not in others. In order to settle this question, a population-based cohort consisting of 62,615 patients who had undergone cholecystectomy was followed up for the occurrence of pancreatic and periampullar cancer up to 23 years. After excluding the first year after operation, there were 261 pancreatic cancers vs 216.8 expected [standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI) = 1.06-1.37]; and 11 periampullar cancers vs 7.2 expected (SIR = 1.52; 95% CI = 0.76-2.72). The increased risk of pancreatic cancer was most prominent up to four years after operation, but was also significantly increased 15 years or more after operation (SIR = 1.35; 95% CI = 1.00-1.78). We conclude that there is a modest excess risk of pancreatic and periampullar cancer following cholecystectomy, most prominent up to four years after operation, but that also exists 15 years or more after operation.

Ampulla of Vater↗

PubMed1996

Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in monitoring of therapy.

CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of nasopharyngeal carcinoma and 19 patients who developed distant metastases. A reference range of < 2 U/ml for our local Chinese population was established in 55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients had significantly higher marker levels than the healthy controls and the mean level increased with advancing stage. However, the low percentage of elevation in early stages means that the marker is not useful for screening. The overall percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of the nasopharynx is comparable to that of squamous cell carcinoma of the lungs, suggesting that the expression of CYFRA 21-1 is related to the cell type rather than the tissue type of the carcinoma, 46 (95.8%) of 48 patients with metastatic nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely high percentage implies that it is very unlikely for a patient with a normal value to have distant metastasis. This may permit major economies in radiological screening for distant metastasis. Preliminary results from serial measurement of the marker indicated its potential for monitoring response to treatment and for early detection of distant metastasis.

Biomarkers, Tumor↗

PubMed1996

Isoelectric focusing of alphafetoprotein in patients with hepatocellular carcinoma--frequency of specific banding patterns at non-diagnostic serum levels.

Serum levels of alphafetoprotein are raised in 60-80% of patients with hepatocellular carcinoma. Although widely used as a serum marker, frequent false-positive results in patients with benign liver disease, result in poor specificity. This occurs particularly when levels of alphafetoprotein fall between 50-500 ng ml-1, the so-called 'grey area'. Recent reports suggest that isoelectric focusing of alphafetoprotein demonstrates certain bands that are more specific for hepatocellular carcinoma. Our aim was to determine whether the apparent specificity of this new approach is gained at the expense of decreased sensitivity. Sera from 110 patients with a 'non-diagnostic' serum alphafetoprotein level (50-500 ng ml-1) were examined by isoelectric focusing and quantified by densitometric scanning. Ten patients with chronic liver disease and a raised serum alphafetoprotein level (50-500 ng ml-1), but with no evidence of hepatocellular carcinoma, were also studied. Isoelectric focusing revealed characteristic hepatocellular carcinoma bands (bands +II and +III) in 96% patients overall, and 100% of those with levels of total alphafetoprotein greater than 100 ng ml-1. No such bands were seen among ten subjects with cirrhosis but without hepatocellular carcinoma. Bands that are characteristic of hepatocellular carcinoma (bands +II or +III) are seen in the great majority of hepatocellular carcinoma patients; their absence makes a diagnosis of hepatocellular carcinoma extremely unlikely.

Carcinoma, Hepatocellular↗

PubMed1996

Second primary cancers in patients with cutaneous malignant melanoma: a population-based study in Sweden.

To quantify the risk of second primary cancers among patients with cutaneous malignant melanoma, we studied 20,354 patients in the Swedish Cancer Register during 1958-88. A second primary cancer was reported in 1605 patients, compared with an expected number of 1109.5 [standardised incidence ratio (SIR) = 1.45, 95% confidence interval (CI) = 1.38-1.52]. The highest risk was found among patients younger than 60 years. The greatest risk was seen during the first year after diagnosis (SIR = 1.91, CI = 1.69-2.14), but even after long-term follow-up--15 years or more--the risk was still significantly elevated (SIR = 1.56, CI = 1.35-1.79). The strongest association was found for a second primary malignant melanoma (men, SIR = 10.0, CI = 8.26-12.00; women, SIR = 8.66, CI = 7.22-10.30) and non-melanoma skin cancer (men, SIR = 3.58, CI = 2.85-4.44; women, SIR = 2.41, CI = 1.71-3.29). The risk of second cancers associated with tissues of neuroectodermal origin was increased, especially tumours of the nervous system (men, SIR = 1.73, CI = 1.10-2.60; women, SIR = 2.03, CI = 1.45-2.78). The SIR of second cancers involving the immune system was also increased. An excess risk of endometrial cancer was seen (SIR = 1.41, CI = 1.03-1.88), but no significant associations existed for cancers of the breast, ovary, testis or other endocrine glands. Among tumours of the digestive tract, only colon cancer in men had a significantly increased SIR (1.33, CI = 1.00-1.74).

Age Factors↗

PubMed1996

The accuracy of skin self-examination for atypical nevi.

We conducted a validation study to assess laypersons' ability to self-report atypical nevi. Study subjects were drawn from a large population-based cohort of middle-aged Swedish women who had responded to a previous health survey. The health survey questionnaire included color photographs of atypical nevi. Respondents were asked to examine their lower extremities for similar lesions. We invited 500 survey respondents to participate in a physician-conducted skin examination; 400 (80%) subjects agreed. We compared the results of skin self-examination for atypical nevi to the results of the physician-conducted skin examination. Using methods developed for this study, we estimated sensitivity as 29% and specificity as 85%. Positive predictive value was 20%; negative predictive value was 90%. We estimated that 12% of Swedish women have atypical nevi on the lower extremities. Although these findings suggest poor accuracy of skin self-examination for atypical nevi, our results may have been adversely affected by limiting self-examination to the legs and by the severity of atypical nevi shown in the comparison photographs used by survey respondents.

Adult↗

PubMed1996

Primary mediastinal malignant germ cell tumour. Single institution experience in Chinese patients and correlation with specific alpha-fetoprotein bends.

Ten Chinese patients were reviewed, all with mediastinal germ cell tumours and treated in our centre during the past 8 years. Three patients with pure seminomas were given chemotherapy with or without radiotherapy. AB achieved complete remission with no relapse. Seven patients with non-seminomatous germ cell tumours (NSGCT) were given chemotherapy, with or without surgery. Two patients with rapid decay of alpha-fetoprotein (AFP) levels (half-life less than or equal to 7.2 days) during chemotherapy achieved complete remission with no relapse. Five patients with prolonged decay of AFP levels (half-life > 7.2 days) failed to achieve complete remission with initial chemotherapy and all but one patient died between 5 and 9 months later. One patient developed acute megakaryocytic leukaemia. Using isoelectric focusing, AFP bands specific to NSGCT were quantified, and comparison was made with the total AFP in five cases. In each case the change in NSGCT-specific AFP concentration in response to therapy closely paralleled that of total AFP. Estimation of NSGCT-specific AFP offers no apparent advantage in monitoring disease response or progression.

Adult↗

PubMed1996

Cigarette smoking and breast cancer.

A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

Age Factors↗

PubMed1995

The risk of esophageal cancer in patients with achalasia. A population-based study.

OBJECTIVE: To determine more precise and accurate cancer risk estimates for achalasia that could be used to plan surveillance. DESIGN: Cohort. SETTING: Swedish population. PARTICIPANTS: All patients with achalasia listed in the population-based Swedish Inpatient Register from 1964 through 1989. MAIN OUTCOME MEASURES: The observed number of cancers in the cohort was compared with expected numbers of cancers (standardized incidence ratio [SIR]) for each 5-year age group and calendar year of observation, calculated using data from the Swedish Cancer Registry. RESULTS: A total of 1062 patients with achalasia accumulated 9864 years of follow-up. The mean age at entry was 57.2 years, and the mean age at cancer diagnosis was 71.0 years. Esophageal cancer occurred in 24 patients. The risk of esophageal cancer in the first year after achalasia diagnosis was extremely high (SIR, 126.3; 95% confidence interval [CI], 63.0 to 226.1) as a consequence of prevalent cancers leading to distal esophageal obstruction simulating achalasia. During years 1 to 24, the risk was increased more than 16-fold (SIR, 16.6; 95% CI, 8.8 to 28.3). Annual surveillance after the first year would require 406 endoscopic examinations in men and 2220 in women to detect one cancer. CONCLUSIONS: Patients with achalasia are at markedly increased risk of developing esophageal cancer. A substantial number of surveillance examinations might be required to screen for cancers, especially in women. It is not known whether surveillance will result in improved survival.

Adult↗

PubMed1995

Evidence of an association between non-Hodgkin's lymphoma and skin cancer.

OBJECTIVE: To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkin's lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non-Hodgkin's lymphoma and skin cancer was studied. DESIGN: Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. SETTING: Denmark (1943-89) and Sweden (1958-89). SUBJECTS: Four population based cohorts identified in the nationwide cancer registries (34,641 people with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukaemia, 34,989 with malignant melanoma, 25,980 with squamous cell skin cancer). A total of 562,085 person years were accrued for the analysis. MAIN OUTCOME MEASURES: The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. RESULTS: The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non-Hodgkin's lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non-Hodgkin's lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. CONCLUSIONS: The occurrence of non-Hodgkin's lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkin's lymphoma in recent decades.

Age of Onset↗

PubMed1995

Germ cell tumors express a specific alpha-fetoprotein variant detectable by isoelectric focusing.

BACKGROUND: Many nonseminomatous germ cell tumors (NSGCTs) express elevated levels of serum alpha-fetoprotein (AFP), which is widely used for diagnosis and monitoring therapy. Alpha-fetoprotein is also expressed in patients with hepatocellular carcinoma (HCC). In these sera, several variants, some highly specific, recently have been detected by isoelectric focusing. METHODS: Sera were collected from nine patients with NSGCTs, five pregnant women, and five patients with HCC. After isoelectric focusing, the proteins were transferred to nitrocellulose membrane by blotting and incubated with polyclonal rabbit antihuman AFP conjugated with horseradish peroxidase. The enhanced chemiluminescence detection system and Hyperfilm-ECL were used to render the protein bands visible and each was quantified as a percentage of the total AFP using a densitometer. RESULTS: Isoelectric focusing of serum alpha-fetoprotein from the patients with NSGCTs (four testicular, five mediastinal) revealed a consistent pattern characterized by a specific band (band +III). A second band (band +II) that is also seen in sera from patients with hepatocellular carcinoma was present in all patients. The overall pattern was distinct from that of AFP from HCC and that produced during late pregnancy. The two characteristic bands (AFP +II and +III) were responsible for the great majority of total AFP in these patients; estimation of serial sera in patients undergoing treatment showed that total and "malignant" AFP changed in parallel. Banding patterns, apart from one patient, were identical in patients with testicular and mediastinal NSGCTs. CONCLUSION: NSGCTs tumors express a highly consistent and specific pattern of AFP variants. More detailed analysis of AFP patterns in larger numbers of patients may provide further insight into the cellular heterogeneity of germ cell tumors.

Adolescent↗

PubMed1995

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells.

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

Amino Acid Oxidoreductases↗

PubMed1994

Risk factors for oesophageal cancer in northeast China.

A hospital-based case-control study of oesophageal cancer was carried out in the Heilongjiang Province, a low-risk area for oesophageal cancer in China. From May 1985 to May 1989, 196 histologically confirmed cases and 392 controls with other (non-neoplastic) diseases were personally interviewed in the wards of 5 major hospitals. Information was obtained about usual consumption in the early 1980s of 32 major contributors to the diet in the province, socio-demographic status, smoking and alcohol consumption. Odds ratios (OR) were obtained from logistic regression models, and confounding was controlled by means of multivariate models. Smoking and alcohol consumption were major risk factors for oesophageal cancer in this population. Smokers of handmade cigarettes exhibited a particularly high risk. A near multiplicative synergism was found between smoking and alcohol consumption. There was a significant inverse dose-risk trend for combined consumption of vegetables and fruits; a 300-g increase per day lowered risk by 35%. Vitamin C intake was negatively associated with risk; a 100-mg increase per day lowered risk by 39%. Our data suggest a modifying effect of vitamin C and beta-carotene on risk associated with smoking, but the power of analyses was low. Salt, salt-preserved foods and pickled vegetables were not associated with increased risk. High temperature of meals and drinks was a strong risk indicator in this population. The strength of tea and overall tea consumption were independent determinants of the risk.

Adult↗

PubMed1994

A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia: exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix.

We have identified a large family with a dominantly inherited chondrodysplasia characterized by a waddling gait, short limbs, and early onset osteoarthritis. The radiographic presentation resembles pseudoachondroplasia in childhood and multiple epiphyseal dysplasia in adults. Electron microscopic examination of cartilage reveals accumulation of material within the rough endoplasmic reticulum similar to that seen in pseudoachondroplasia and the Fairbank type of multiple epiphyseal dysplasia. By linkage analysis, we have excluded the genes for aggrecan, decorin, hexabrachion (tenascin), type II procollagen, the alpha 1 chain of type XI procollagen, the alpha 1 chain of type IX procollagen, and link protein, candidate genes that encode structural components of the cartilage extracellular matrix, as the disease locus for this disorder.

Abnormalities, Multiple↗

PubMed1994

Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study.

BACKGROUND/AIMS: The risk of colorectal cancer increases in patients with ulcerative colitis, most markedly among young patients and/or those with extensive disease at onset. However, it is unknown whether individual risk can be predicted more precisely and whether cancer risk can be reduced by long-term treatment with sulfasalazine. METHODS: In a population-based cohort of 3112 patients with ulcerative colitis, we compared 102 cases of colorectal cancer and 196 matched controls without cancer. Hospital records were used to abstract information on pharmacological therapy, disease activity, and extraintestinal manifestations. The relative risk (RR) of cancer was estimated by conditional logistic regression. RESULTS: Pharmacological therapy, especially sulfasalazine, lasting at least 3 months was associated with a significant protective effect (RR, 0.38; 95% confidence interval [CI], 0.20-0.69) independent of disease activity. There was also a tendency to an independent protective effect for cigarette smoking (RR, 0.15; 95% CI, 0.02-1.25) and higher disease activity (RR, 0.80; 95% CI, 0.49-1.33). CONCLUSIONS: The risk of colorectal cancer among patients with ulcerative colitis can be reduced through pharmacological therapy. This finding is consistent with the reports of a protective effect of aspirin among individuals in the general population.

Adolescent↗

PubMed1994

Season of birth and breast cancer risk in Sweden.

Recent research suggests that intrauterine exposures, perhaps factors that influence birth weight and other indicators of fetal growth, may affect future breast cancer risk. Because birth weight shows seasonal variation in Sweden, we assessed whether risk for breast cancer is associated with month of birth. The analyses included all 115,670 women, born between 1858 and 1968, who were reported to the Swedish Cancer Registry in 1958-89 as having breast cancer. Poisson regression models were used to examine the data. After adjustment for seasonality of number of live births in the population at risk, a significant seasonal pattern was identified for women born between 1880 and 1920. Women born in June had a 5% higher risk of breast cancer than those born in December. By contrast, there was no evidence of birth seasonality among 440,948 women with cancer at other sites. Exposures relevant to breast cancer risk later in life are unlikely to be related to month of birth. Thus, prenatal or early post-natal factors influence breast carcinogenesis, but the seasonal variation in these factors must have decreased over time.

Breast Neoplasms↗

PubMed1994

Localization and regulation of endothelial NO synthase mRNA expression in rat kidney.

Nitric oxide (NO) has effects on renal blood flow, glomerular filtration rate, renin secretion, and renal sodium excretion. Four isoforms of nitric oxide synthase (NOS) have been cloned to date. However, the molecular identity of NOS present in the renal vasculature is unknown. Endothelial NOS (NOS-III) is regulated both acutely by cell calcium and chronically by shear stress. To determine if renal blood vessels and the glomerulus express NOS-III mRNA, we used degenerate polymerase chain reaction (PCR) to clone a portion of rat NOS-III. We then assayed NOS-III mRNA in microdissected renal structures by reverse transcriptase-PCR. NOS-III mRNA was expressed at high levels in glomeruli, arcuate vessels, and interlobular artery/afferent arterioles. NOS-III mRNA was detected inconsistently in proximal tubules, thick ascending limbs, and cortical and inner medullary collecting ducts. Previous studies have shown that chronic oral treatment with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) decreases NO synthesis and causes hypertension. To determine if the systemic blockade occurs only by competitive inhibition, we determined the effect of L-NAME on glomerular NOS-III mRNA. L-NAME administration (5 days) decreased NOS-III mRNA in the glomerulus to 25 +/- 12% of control levels. We conclude that endothelial NOS-III mRNA is preferentially expressed in the glomerulus and renal vasculature, where it can modulate renal blood flow and glomerular filtration rate. Furthermore, glomerular NOS-III may be modulated at the level of mRNA abundance in vivo by systemic L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1994

Family-centered care: thriving in Hawaii under Part H.

Hawaii's system of prevention and early intervention embodies Part H principles that a child with a disability is first surrounded by a family, then by a community. Since 1986, families in Hawaii have been active in early intervention, first by persuading the governor to name the Department of Health as the lead agency, and then by writing much of the original grant application, interviewing and selecting staff members, and serving on the Hawaii Early Intervention Coordinating Council and its subcommittees. Families helped develop Hawaii's broad definition of the population to be served and were vocal advocates before the legislature to obtain funding for the program. Under Part H, Hawaii serves 6% of all children under the age of three, a larger percentage than any other state. Services focus on the family's needs as much as on the child's. The Individualized Family Support Plan (IFSP), developed jointly by the parents and professionals, recognizes families as the final decision-maker on the IFSP team. Families choose options that fit their needs. IFSP meetings are at times and places convenient to families and, to the extent feasible, in the family's native language. Care coordinators, of whom several are parents of children with special needs, monitor services to ensure that families receive quality care. Families receive (1) services at no cost, (2) preference when applying for positions in the Zero-to-Three Hawaii Project, and (3) compensation when serving in advisory or policy-making areas. In Hawaii, families are the center of early intervention services.

Audiology↗