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Biomedical subjects

J Lynch

Publications and source records attributed to J Lynch.

At least 73 records · Page 4Linked to original sources

Therapeutic strategies for localized prostate cancer I: surgery, ultrasound, adjuvant and neoadjuvant therapy.

Over the past decade, because of the introduction and widespread availability of prostate-specific antigen determinations, carcinoma of the prostate that is localized and potentially curable has been diagnosed in an increasing number of men. Advances in surgical management with preservation of the neurovascular bundles, in addition to hormone therapy, have added to the success and improved quality of life of patients undergoing treatment. New forms of treatment (including laparoscopic prostatectomy and high-intensity focused ultrasound) are advances that are continuing to be developed and that may have a significant role in the management of this disease. With further investigation and technologic advancement, it is anticipated that more and more men with localized disease will be identified and cured, with preservation of sexual and urinary function.

Journal Article↗

Relation between income inequality and mortality: empirical demonstration.

OBJECTIVE: To assess the extent to which observed associations at population level between income inequality and mortality are statistical artefacts. DESIGN: Indirect "what if" simulation by using observed risks of mortality at individual level as a function of income to construct hypothetical state level mortality specific for age and sex as if the statistical artefact argument were 100% correct. SETTING: Data from the 1990 census for the 50 US states plus Washington, DC, were used for population distributions by age, sex, state, and income range; data disaggregated by age, sex, and state from the Centers for Disease Control and Prevention were used for mortality; and regressions from the national longitudinal mortality study were used for the individual level relation between income and risk of mortality. RESULTS: Hypothetical mortality, while correlated with inequality (as implied by the logic of the statistical artefact argument), showed a weaker association with states' levels of income inequality than the observed mortality. CONCLUSIONS: The observed associations in the United States at the state level between income inequality and mortality cannot be entirely or substantially explained as statistical artefacts of an underlying individual level relation between income and mortality. There remains an important association between income inequality and mortality at state level over and above anything that could be accounted for by any statistical artefact. This result reinforces the need to consider a broad range of factors, including the social milieu, as fundamental determinants of health.

Adult↗

Failure to diagnose hereditary colorectal cancer and its medicolegal implications: a hereditary nonpolyposis colorectal cancer case.

PURPOSE: We describe a patient who had precancerous colonic symptoms and a positive family history of multiple occurrences of early-onset colorectal cancer in her first-degree and second-degree relatives consistent with hereditary nonpolyposis colorectal cancer. Hereditary nonpolyposis colorectal cancer diagnosis had not been made before her diagnosis of carcinoma of the cecum with liver metastasis. She died at age 20, leading to litigation. Controversies about standards of care, their malpractice implications, and pertinent legal issues are discussed. METHODS: Review of the medical and family history was made by the expert witness (HTL) with appropriate documentation of the chronology of symptoms, as derived from depositions. These documents revealed that the patient's mother had repeatedly discussed with the caregivers her concern about the family history of colon cancer and the need for appropriate surveillance. RESULTS: The patient's colonic symptoms progressed for a period of three years. Flexible sigmoidoscopy was performed by a nonphysician. The physician who ordered the procedure considered this appropriate because isolated polyps were reported in the patient's father and paternal uncle, which apparently led him to believe that the diagnosis was familial adenomatous polyposis. During litigation procedures, a pedigree was constructed and found to be consistent with hereditary nonpolyposis colorectal cancer. The case was settled in favor of the plaintiff before trial. CONCLUSION: It is essential to understand the natural history of hereditary nonpolyposis colorectal cancer, inclusive of the need for surveillance colonoscopy in patients at increased risk by virtue of their position in their family pedigree.

Adenomatous Polyposis Coli↗

Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis.

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by formation of multiple schwannomas and meningiomas due to inactivating mutations in the NF2 tumor suppressor gene on chromosome 22. We describe a polymorphism in the 3' untranslated region of the NF2 gene that is informative in about one-third of individuals. This polymorphism permitted an assessment of the relative expression of NF2 transcripts in lymphoblastoid cell RNA from 22 unrelated NF2 patients heterozygous for a germline NF2 mutation, along with 6 schwannomatosis patients, and 14 unaffected controls. Unequal allelic expression (1.8- to 20-fold) was detected in 15 of the NF2 cases, but in none of the schwannomatosis or control individuals. Underexpression of the NF2 mutant allele was documented for all 6 nonsense or frameshift mutations, 3 of 6 splice mutations, and 1 of 4 missense mutations, which, unexpectedly, was shown to alter the NF2 transcript and create a premature stop codon. In contrast, equal expression or slight overexpression of NF2 mutant alleles was observed for 2 in-frame deletions, 2 splice alterations, and 3 missense mutations. In the remaining 5 cases, the allele representing the mutant transcript was not known. Thus, truncating NF2 mutations, which are the most frequent alterations in NF2 patients and NF2-associated tumors, were associated with underexpression of the mutant allele, whereas the less common in-frame alterations usually showed normal or slight overexpression of the mutant transcript.

Alleles↗

Bacterial vaginosis and past chlamydial infection are strongly and independently associated with tubal infertility but do not affect in vitro fertilization success rates.

OBJECTIVE: To determine the incidence of active vaginal infection in women undergoing IVF, relate it to the cause of infertility, and investigate a relation with the outcome of fresh ET. DESIGN: Cross-sectional study. SETTING: Tertiary care infertility referral center. PATIENT(S): Two hundred eighty-six women who underwent 344 oocyte recovery procedures for IVF cycles between March 1997 and January 1998. INTERVENTION(S): High vaginal swab specimens and endocervical swab specimens were obtained and ELISA serology was performed for detection of Chlamydia species on samples taken immediately before oocyte recovery. The results were related to the cause of infertility and the outcome parameters. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Seropositivity for Chlamydia species and the presence of bacterial vaginosis both were strongly and independently associated with tubal disease. There was no difference in pregnancy rates in any of the groups regardless of their serologic status for chlamydial infection or current infection with bacterial vaginosis. CONCLUSION(S): This study provides further evidence of the pelvic pathogenicity of bacterial vaginosis. However, it shows that women who have bacterial vaginosis or who have been treated for chlamydial infection in the past achieve pregnancy rates with IVF treatment similar to those of women who have no evidence of such infections.

Adult↗

An update on DNA-based BRCA1/BRCA2 genetic counseling in hereditary breast cancer.

The identification of BRCA1 and BRCA2 mutations has enabled physicians to identify persons at high risk for carcinoma of the breast and ovary in hereditary breast-ovarian cancer (HBOC) families. Many physicians have limited knowledge about the effective translation of these new discoveries into clinical practice settings. This problem is further confounded by the limited number of genetic counselors who have experience with cancer genetics. Genetic counseling about DNA test results was provided to 420 patients from 37 HBC/HBOC families. Descriptive data were collected and recorded about their responses to questions posed immediately before and after test results were disclosed. Findings disclosed a significant tendency of patients to overestimate rather than underestimate their risk (P < .001) prior to receiving results. The chief reason for declining to receive results was fear of insurance discrimination. The primary reason that patients sought test results was for their children. Most women reported that, if testing identified them as mutation carriers, they would consider lifetime surveillance and prophylactic surgery. Responses to DNA test results were varied and often unpredictable. Counseling by an appropriately educated and skilled professional is essential to assist people in making decisions regarding testing and health management.

Adult↗

Male breast cancer in the hereditary nonpolyposis colorectal cancer syndrome.

A male member of a large HNPCC kindred, affected by primary malignancies of the breast and colon, was identified. This individual was found to harbor a germline mutation of the MLH1 mismatch repair gene previously shown to segregate with disease in this kindred. The breast tumor exhibited somatic reduction to homozygosity for the MLH1 mutation, and microsatellite instability was evident in the breast tumor. We conclude that hereditary male breast cancer can occur as an integral tumor in the HNPCC syndrome.

Aged↗

Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement.

UNLABELLED: We assessed the analgesic efficacy of postoperative epidural ropivacaine 0.1% with and without sufentanil 1 microgram/mL in this prospective, randomized, single-blinded study of 30 ASA physical status I-III patients undergoing elective total hip replacement. Lumbar epidural block using 0.75% ropivacaine was combined with either propofol sedation or general anesthesia for surgery. After surgery, the epidural infusion was commenced. Fifteen patients in each group received either an epidural infusion of 0.1% ropivacaine with 1 microgram/mL sufentanil (R + S) or 0.1% ropivacaine without sufentanil (R) at a rate of 5-9 mL/h. All patients had access to i.v. piritramide via a patient-controlled analgesia device. The R + S group consumed six times less piritramide over a 48-h infusion period than the R group (median 12.7 vs 73.0 mg; P < 0.001). Motor block was negligible for the study duration in both groups. Patient satisfaction was excellent. The incidence of adverse events, such as nausea, was similar. We conclude that a continuous epidural infusion of 0.1% ropivacaine with 1 microgram/mL sufentanil is more effective than ropivacaine alone in treating pain after elective hip replacement without motor block. IMPLICATIONS: This is the first randomized study comparing the efficacy of the epidural combination of ropivacaine 0.1% and sufentanil 1 microgram/mL versus plain ropivacaine 0.1% in treating pain after hip replacement. We found that ropivacaine 0.1% and sufentanil 1 microgram/mL led to a sixfold reduction in opioid requirements after total hip replacement by producing a negligible motor block.

Adult↗

Lung transplantation: a decade of experience.

OBJECTIVE: To review the 10-year clinical experience of a single institution's adult lung transplant program. METHODS: Since July 1988, 450 lung transplants have been performed in 443 patients. Recipient diagnoses included emphysema in 229 patients, cystic fibrosis in 70 patients, pulmonary fibrosis in 48 patients, pulmonary hypertension in 49 patients, and miscellaneous end-stage lung diseases in 47 patients. Single-lung transplant was performed in 157 cases, bilateral sequential lung transplant in 283 cases, en bloc double-lung transplant in 8 cases, and heart-lung transplant in 2 cases. Graft lungs were obtained from local donors in 24% of cases and from distant donors in 76% of cases. Ideal donors were used in 74% of cases; in 26%, the donor was classified as marginal based on objective criteria. RESULTS: Four hundred six (91.6%) lung transplant recipients survived to hospital discharge. There were 37 hospital deaths from cardiac events (n = 8), primary graft failure (n = 8), sepsis (n = 6), anastomotic dehiscence (n = 6), and other causes (n = 9). A diagnosis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) was made in 191 patients (42.5%). BOS has not been improved by any specific therapy. Rates of freedom from BOS at 1, 3, and 5 years after the transplant are 82%, 42%, and 25%. One-, 3-, and 5-year actuarial survival rate for the entire group are 83%, 70%, and 54%. There is no statistical difference in survival according to diagnosis or type of lung transplant. Recipient waiting time was 116 days in the first 90 patients and 634 days in the most recent 90 patients. CONCLUSIONS: Lung transplantation offers patients with end-stage lung disease acceptable prospects for 5-year survival. Chronic rejection and long waiting lists for donor lungs continue to be major problems facing lung transplant programs. The use of marginal and distant donors is a successful strategy in improving donor availability.

Adult↗

Intravenous titration with morphine for severe cancer pain: report of 28 cases.

BACKGROUND: In a multicenter study, 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization (WHO) were switched to oral slow-release morphine. METHODS: Patients received intravenous morphine through a patient-controlled pump (PCA) for the first 24 hours (bolus = 1 mg, lockout interval = 5 minutes, maximum dose = 12 mg/hour). From day 2 patients were treated with oral slow-release morphine. Daily doses were calculated from the requirements of the day before. Breakthrough pain was treated with PCA until stable doses were reached (<2 boluses/day) and then with oral immediate-release morphine solution. Pain intensity was reported in a diary four times a day, in addition to mood, activity, and quality of sleep once daily. RESULTS: Mean duration until adequate pain relief reported (<30 on a 101-step numerical scale; NRS) was 5 hours (range = 80-620 minutes). Mean pain intensity was reduced from 67 NRS to 22 NRS. Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14. Serious adverse events such as respiratory depression were not observed. Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction. Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good. CONCLUSIONS: Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain. Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration.

Administration, Oral↗

Income inequality, social cohesion, and class relations: a critique of Wilkinson's neo-Durkheimian research program.

Wilkinson's "income inequality and social cohesion" model has emerged as a leading research program in social epidemiology. Public health scholars and activists working toward the elimination of social inequalities in health can find several appealing features in Wilkinson's research. In particular, it provides a sociological alternative to former models that emphasize poverty, health behaviors, or the cultural aspects of social relations as determinants of population health. Wilkinson's model calls for social explanations, avoids the subjectivist legacy of U.S. functionalist sociology that is evident in "status" approaches to understanding social inequalities in health, and calls for broad policies of income redistribution. Nevertheless, Wilkinson's research program has characteristics that limit its explanatory power and its ability to inform social policies directed toward reducing social inequalities in health. The model ignores class relations, an approach that might help explain how income inequalities are generated and account for both relative and absolute deprivation. Furthermore, Wilkinson's model implies that social cohesion rather than political change is the major determinant of population health. Historical evidence suggests that class formation could determine both reductions in social inequalities and increases in social cohesion. Drawing on recent examples, the authors argue that an emphasis on social cohesion can be used to render communities responsible for their mortality and morbidity rates: a community-level version of "blaming the victim." Such use of social cohesion is related to current policy initiatives in the United States and Britain under the New Democrat and New Labor governments.

Community Health Planning↗

The social class determinants of income inequality and social cohesion.

The authors argue that Wilkinson's model omits important variables (social class) that make it vulnerable to biases due to model mis-specification. Furthermore, the culture of inequality hypothesis unnecessarily "psychopathologizes" the relatively deprived while omitting social determinants of disease related to production (environmental and occupational hazards) and the capacity of the relatively deprived for collective action. In addition, the hypothesis that being "disrespected" is a fundamental determinant of violence has already been refuted. Shying away from social mechanisms such as exploitation, workplace domination, or classist ideology might avoid conflict but reduce the income inequality model to a set of useful, but simple and wanting associations. Using a nonrecursive structural equation model that tests for reciprocal effects, the authors show that working-class position is negatively associated with social cohesion but positively associated with union membership. Thus, current indicators of social cohesion use middle-class standards for collective action that working-class communities are unlikely to meet. An erroneous characterization of working-class communities as noncohesive could be used to justify paternalistic or punitive social policies. These criticisms should not detract from an acknowledgment of Wilkinson's investigations as a leading empirical contribution to reviving social epidemiology at the end of the century.

Authoritarianism↗