Biomedical subjects

P Cane

Publications and source records attributed to P Cane.

17 recordsLinked to original sources

PubMed2001

Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1.

Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resistant mutations in a significant number of patients. The virological and biochemical responses of 8 patients coinfected with HBV/HIV-1 treated with both lamivudine and famciclovir were studied. Patients exhibiting HBV viral rebound at 1 year were analyzed for the emergence of HBV polymerase mutations. Only 1 patient had no prior exposure to lamivudine. Addition of famciclovir to the treatment regimen resulted in a median fall in HBV DNA level of 0.33 log(10) at 3 months and an overall rise in HBV DNA level of 3 log(10) at 12 months. The only patient in whom durable viral suppression and HBV e antigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-associated mutations in 6 of 7 patients with viral rebound. Sequential nucleoside analogue therapy is unlikely to be successful in achieving long-term suppression of HBV replication, and combination therapy should be considered at treatment initiation.

2-Aminopurine↗

PubMed2001

Variation in vaginal breech delivery rates by hospital type.

OBJECTIVE: To relate vaginal breech delivery rates to the following hospital types: public, health maintenance organization, private teaching, or private nonteaching. METHODS: In a retrospective study using administrative discharge data from Los Angeles County, California, we calculated the vaginal breech delivery rates of singleton breech deliveries during calendar years 1988 and 1991. RESULTS: Ten thousand four hundred breech deliveries were identified, 8988 (86.4%) term and 1412 (13.6%) preterm. Twelve percent (1252 of 10,400) were vaginal deliveries (10.1% term and 24.5% preterm). Term vaginal breech deliveries varied by hospital type and were more frequent in public hospitals (28.4%, 95% confidence interval [CI] 26.1%, 30.7%) and less frequent in private nonteaching hospitals (5.4%, 95% CI 4.8%, 5.9%). Term vaginal deliveries were 2.4 to 11.3 times more likely among black women and 1.3 to 6.3 times more likely for Hispanic women across all hospital types, compared with white women in private nonteaching hospitals. There was no difference in the proportion of preterm vaginal breech deliveries by hospital type (mean 24.5%). However, with the exception of public hospitals, the proportion of vaginal breech deliveries for both term and preterm deliveries varied significantly by ethnicity. CONCLUSION: The use of vaginal breech delivery varied by hospital type and patient ethnicity. Within private teaching and nonteaching hospitals, vaginal breech delivery was more likely for black women than for women of other ethnic groups. Further study is needed to understand the hospital policies or organizational factors, as well as the patient-related sociocultural and clinical factors, that contribute to those differences.

Adult↗

PubMed2001

Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir.

BACKGROUND: Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure. CASE REPORT: A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the development of graft failure. OUTCOME: A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved. CONCLUSION: The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.

Acute Disease↗

PubMed2000

Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient.

BACKGROUND: In many transplant centres lamivudine is an important component of prophylaxis against, and treatment of, hepatitis B virus (HBV) graft infection. Drug resistant HBV species with specific polymerase mutations may emerge during lamivudine treatment. AIMS: To examine the clinical consequences of graft infection by lamivudine resistant virus. METHODS: The clinical course of four liver transplant patients who developed graft infection with lamivudine resistant virus was reviewed. The response of HBV infection to reduction of immunosuppression and to manipulation of antiviral therapy was assessed. For each patient, serum viral titre was measured and the viral polymerase gene was sequenced at multiple time points. RESULTS: High serum titres were observed following emergence of the lamivudine resistant species. Wild type HBV re-emerged as the dominant serum species after lamivudine withdrawal. All patients developed liver failure, and onset of liver dysfunction was observed when resistant virus was the dominant serum species. In three patients, liver recovery was observed when immunosuppression was stopped and when alternative antivirals were given. Wild type virus appeared to respond to ganciclovir, and to reintroduction of lamivudine. For one patient, introduction of famciclovir was associated with clinical, virological, and histological response. CONCLUSIONS: Failure of lamivudine prophylaxis may identify patients at special risk for the development of severe graft infection. Treatment of graft reinfection should include reduction of immunosuppression, and systematic exposure to alternative antivirals. Viral quantitation and genetic sequencing are essential components of therapeutic monitoring.

Adult↗

PubMed2000

Additive antiviral effects of lamivudine and alpha-interferon in chronic hepatitis B infection.

alpha-Interferon has limited efficacy against chronic hepatitis B virus (HBV) infection. Nucleoside analogues may confer greater benefits, however, it is likely that combination therapies will be required for effective control of this infection. We investigated the antiviral effect of lamivudine and interferon therapy in eight patients with high HBV-DNA levels. Six patients received lamivudine/interferon combination therapy followed, after a 6-month drug-free period, with lamivudine monotherapy. Mean HBV viral load (copies/ml) reduction was significantly greater after 4 months of combination therapy (4.3 x 10(3)) compared to an equivalent period of lamivudine monotherapy (2.9 x 10(2)) (P=0.03). Two patients were given 6 months of lamivudine/interferon combination therapy followed immediately by lamivudine monotherapy. Cessation of interferon in these patients led to a rapid 1-2 log10 increase in HBV viral load. These findings suggest that alpha-interferon has a direct antiviral effect on chronic HBV infection, which may be additive to, or synergistic with lamivudine.

Antiviral Agents↗

PubMed1999

Vaginal birth after cesarean and uterine rupture rates in California.

OBJECTIVE: To describe attempted and successful vaginal birth after cesarean (VBAC) rates and uterine rupture rates for women with and without prior cesareans, and compare delivery outcomes in hospitals with different attempted VBAC rates. METHODS: We used California hospital discharge summary data for 1995 to calculate attempted and successful VBAC rates and uterine rupture rates. We used multivariate logistic regression models to evaluate and adjust for age, ethnicity, and payment source. We report the relative risk (RR), attributable fraction, and 95% confidence intervals (CIs) for uterine rupture. RESULTS: There were 536,785 delivery discharges during 1995. The cesarean rate was 20.8%, and 12.5% of women had histories of cesareans. Of women with histories of cesareans, 61.4% attempted VBAC and 34.8% were successful. There were 392 uterine ruptures (0.07%). Women with prior cesareans were 16.98 (95% CI 13.51, 21.43) times more likely to experience uterine rupture, attributable fraction 66% (95% CI 60%, 73%). Among women with prior cesareans, those who attempted VBAC were 1.88 (95% CI 1.45, 2.44) times as likely to have uterine rupture, attributable fraction 34% (95% CI 21%, 46%). Women who delivered in hospitals with high attempted VBAC rates were less likely to have cesarean deliveries, more likely to have successful VBACs, and more likely to experience uterine ruptures. CONCLUSION: Uterine rupture occurs at a low rate in women with and without prior cesarean delivery. Risk of rupture is increased among women with prior cesarean delivery and among those who attempt VBAC.

Adult↗

PubMed1999

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation.

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Antiviral Agents↗

PubMed1998

Hysterectomy in a decade of change: more than a weighty matter.

Objective: Hysterectomy is the second most common surgical procedure performed in the United States. Interest to decrease use of hysterectomy has focused on developing explicit criteria for surgery, peer review and second opinion, as well as changing reimbursement incentives. The purpose of this study is to describe the change in the number of hysterectomies, the indications for hysterectomies, and the histopathology of hysterectomy specimens over the last 10 years at one private, nonprofit, academic, community hospital that does not have a formal system for monitoring hysterectomy use.Methods: Retrospective study utilizing administrative data matched with pathology reports for nonmalignant hysterectomies performed in 1985, 1990, and 1995. Uterine weight and histopathologic diagnoses were recorded. When pathology reports were unavailable, cases were reviewed to determine if the indication was related to prolapse or urinary incontinence. Outcome measures included number of procedures performed, indications for procedures and uterine pathology (uterine weight, histopathology). We utilized the Cochran-Mantel-Haenszel chi(2) and the Kruskal-Wallis rank sum statistic (P <.05).Results: The number of hysterectomies declined from 631 in 1985 to 461 in 1995 (P =.007). The median uterine weight increased (P =.0007), and there was a decrease in the number of specimens with absent histopathology, decreasing from 6% in 1985 to 3% in 1995 (P =.013). This difference was explained by changes in the number of procedures performed on patients with private insurance and HMO reimbursement (P =.018).Conclusions: While the proportion of surgeries performed for specific indications did not change, the number of hysterectomies performed decreased, and there were fewer normal specimens.

Journal Article↗

PubMed1998

The clinical spectrum of respiratory syncytial virus disease in The Gambia.

BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections in early childhood in industrialized countries, but less is known about RSV infection in developing countries. METHODS: Four outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia, West Africa, were studied. RSV was sought by immunofluorescent staining of nasopharyngeal aspirate samples among young children who presented with respiratory infections at three hospitals in the Western Region of the country. RESULTS: Five hundred seventy-four children with RSV infection were identified. The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months, respectively. Sixty-two percent of children <6 months old were boys. Thirteen children (2.4%) had conditions considered to increase the risk of severe RSV infection. On physical examination crepitations were heard in 80% of the children admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%) children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%) were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2 Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV Subgroup A, respectively. CONCLUSIONS: RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It poses a significant burden on the health system, especially through the demand for supplementary oxygen. The clinical spectrum of RSV disease in The Gambia is similar to that seen in developed countries; concomitant bacterial infections are uncommon.

Developing Countries↗

PubMed1995

Tumor marker trends in asymptomatic women at risk for ovarian cancer: relevance for ovarian cancer screening.

The purpose of our study was to examine single and serial determinations of five biomarkers in asymptomatic women at risk for epithelial ovarian cancer to define median values and trends in a cancer-free cohort. Women were enrolled in the Gilda Radner Ovarian Cancer Detection program at Cedars-Sinai Medical Center, Los Angeles, California from July 1, 1991, to July 1, 1993. Biomarkers studied include CA-125, LASA, DM-70K, UGP, and HER-2. Biomarker values that were analyzed included those obtained on the first patient visit and in a subset of values evaluated at 6-month follow-ups. A total of 590 women were included in the study; 425 were premenopausal and 165 were postmenopausal. No one in this study group has developed ovarian cancer within a 12-month follow-up period. Postmenopausal women had significantly lower values for CA-125 (12 vs 19 U/ml, P = 0.0001) and higher values of LASA (16.6 vs 15.4 mg/dl, P = 0.0001), DM/70K (11 vs 0 U/ml, P < 0.001), UGP (3.3 vs 0.3 U/ml, P < 0.001), and HER-2 (12 vs 11 U/ml, P = 0.009) than premenopausal women. Less than 5% of the women had elevated tumor marker values on both screens except for CA-125, where 15% of women studied had two consecutive visits with elevated values (> 35 U/ml). Two women demonstrated an exponential rise in CA-125 between visits. Premenopausal women differ in median biomarker values compared to postmenopausal women. Elevations in single tumor markers, combinations of markers, and exponential increases of markers have all produced false-positive results for ovarian cancer within the 12-month follow-up period. Exponential increases produced the smallest false positive rate (n = 2), but further study and follow-up are needed to determine the efficacy of these tests in ovarian cancer screening.

Adult↗

PubMed1993

Whole-body positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose can detect recurrent ovarian carcinoma.

The existing means of detecting recurrent ovarian carcinoma are notoriously poor. Positron emission tomography (PET) is a form of computer-assisted imaging which produces images reflective of the biochemistry of the tissues rather than their physical characteristics. PET imaging with the positron emitting glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) exploits the accelerated rate of glycolysis characteristic of malignant tissue to image tumors. To begin to study PET's ability to diagnose recurrent ovarian cancer, whole-body PET FDG scanning was performed on 13 patients prior to planned surgical exploration. Seven patients were suspected of having recurrence based upon clinical findings, and 6 patients were clinically free of disease. In all 6 of the patients with suspected recurrence who subsequently underwent surgery, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings. Both intraperitoneal and extraperitoneal lesions were detected by PET. All 6 patients judged clinically free of disease had negative PET scans, but in 5 of these microscopic foci of residual tumor were found at surgery. Although PET FDG cannot replace surgery in the detection of microscopic recurrence, it can accurately detect tumors greater than 1.0 cm in diameter.

Adult↗

PubMed1993

A multidisciplinary approach to the early detection of ovarian carcinoma: rationale, protocol design, and early results.

OBJECTIVE: This study was undertaken to determine the feasibility of currently available tests to detect ovarian cancer at a curable stage. By studying women at risk for the disease on the basis of their family histories of cancer, we hope to gain insight into the genetics and biologic characteristics of ovarian cancer. STUDY DESIGN: Asymptomatic women with a family history of cancer are interviewed by geneticists to obtain accurate pedigree and epidemiologic data. Screening tests including transvaginal ultrasonography, color Doppler imaging, CA 125 measurement, and other investigative biomarkers are performed between cycle days 3 and 8 and repeated biannually. RESULTS: A total of 597 women without symptoms were screened between July 1991 and June 1992. Cystic or complex adnexal masses were detected in 6.2% of patients. A pulsatile index value < 1.0 was measured in 80% of premenopausal patients and 24% of postmenopausal patients, whereas a resistance index value < 0.4 occurred in 12% of premenopausal and 3% of postmenopausal patients. A CA 125 level > 35 U/ml was found in 11.4% of the study participants. To date, one stage IA borderline ovarian tumor and one endometrial carcinoma have been found. CONCLUSIONS: Ovarian cancer screening needs to be investigated in a controlled fashion to determine means that will ultimately improve the survival from the disease.

Adult↗

PubMed1991

Search for the hypoglycemia receptor using the local irrigation approach.

To elucidate the loci for the putative glucoreceptors responding to hypoglycemia we introduced 'brain' and 'liver' clamps. Systemic hypoglycemia was induced by insulin infusion while the area of interest (ie. forebrain, hindbrain, portal-hepatic region) was maintained euglycemic via local glucose irrigation. Utilizing this approach, there appear to be no glucoreceptors residing exclusively in either the forebrain or hindbrain which are essential for the sympathoadrenal response to hypoglycemia. This is true for both moderate and severe hypoglycemic conditions. The possibility of a redundant glucoreceptor system within the brain, as suggested by a subsequent study, remains to be confirmed. The portal-hepatic glucoreceptors appear essential to engendering the full counterregulatory response. Establishing euglycemia across the portal-hepatic region inhibits the sympathoadrenal response to moderate hypoglycemia by over 40%. Further, despite prevailing hypoglycemia and significant elevations in counter-regulatory hormones, the liver demonstrated net glucose extraction during the liver clamp, suggestive of overriding neural input to the liver. Thus, the hepatic afferents appear to be very important for the counterregulatory response to hypoglycemia.

Animals↗

PubMed1991

Hypothermia is critical for survival during prolonged insulin-induced hypoglycemia in rats.

Hypothermia is a well-known concomitant of hypoglycemia in mammals. We tested the hypothesis that this hypothermia is an important adaptive response to hypoglycemia in 11 normal Sprague-Dawley rats. Twelve-hour fasted, conscious animals received primed, continuous insulin infusions for up to 8 hours. Plasma glucose was clamped between 30 and 40 mg/dL and core body temperature was monitored continuously during the insulin infusions. Five of the animals were maintained in a room temperature environment (22 to 24 degrees C) during the hypoglycemia; all became hypothermic (mean +/- SE nadir core temperature, 31 +/- 0.5 degrees C). Spontaneous activity was reduced in these animals, but they remained conscious and responsive to external stimuli. All five returned to normal behavior after euglycemia was restored at the end of the insulin infusions. In the remaining six animals, hypothermia was prevented during hypoglycemia by warming of the air in their cages (mean of hourly core temperatures, 37 +/- 0.1 degrees C). None of these animals survived more than 7 hours. The severity of the hypoglycemia was no greater in the euthermic than in the hypothermic group, as judged by the mean of individual nadir plasma glucose levels (25 +/- 1 v 24 +/- 1 mg/dl, respectively) and by the mean number of glucose values per animal that were less than 30 mg/dL (2 +/- 1 v 7 +/- 1). Plasma osmolality did not change significantly in either group during the period of hypoglycemia, suggesting that dehydration was not the cause of death in the euthermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1988

Response to deep hypoglycemia does not involve glucoreceptors in carotid perfused tissue.

In the present study we examined whether the magnified hormonal counter-regulatory response seen during deep hypoglycemia (40 mg/dl) could be attenuated by supplying the forebrain with glucose furnished through carotid infusion. Two protocols were performed in conscious dogs. In the first protocol we infused glucose bilaterally into the carotid circulation to produce a forebrain glycemia of 55 +/- 1 mg/dl (as reflected in the jugular vein), whereas systemic glycemia declined to 39 +/- 2 mg/dl. In the second protocol as a control we infused glucose into the systemic circulation at a rate matched to protocol 1 so that both systemic and jugular plasma glucose concentrations were equivalent to the systemic glucose concentrations in protocol 1 (jugular, 41 +/- 3 mg/dl; systemic, 40 +/- 2 mg/dl; P greater than 0.9). In spite of a substantial difference in forebrain glycemia (55 mg/dl compared with 41 mg/dl) there were no differences in the counter-regulatory responses of catecholamines or glucagon. In addition, through the use of radiolabeled microspheres, we defined the precise regions of the forebrain irrigated during bilateral intracarotid glucose infusions. The concentration of microspheres was high in the forebrain but very low in the hindbrain. Our results indicate that glucoreceptor cells in tissues perfused by carotid arteries may play a tautological role in the sympathetic response to hypoglycemia and imply that glucose-sensitive receptors must also be located elsewhere in the central nervous system or in the periphery.

Animals↗

PubMed1986

Putative hypothalamic glucoreceptors play no essential role in the response to moderate hypoglycemia.

The response to insulin-induced hypoglycemia includes increased plasma levels of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. This integrated response is thought to be mediated via sympathetic afferent pathways emanating from the ventromedial hypothalamus. However, the precise loci of the receptors that sense glucopenia are not known. In this study, we investigated the importance of putative forebrain glucoreceptors to the systemic response to hypoglycemia. Three protocols were performed. Protocol 1: the systemic response was observed in conscious dogs to hypoglycemia induced by infusion of insulin at a high rate (150 mU/min). Protocol 2: the effect of concomitant bilateral, intracarotid glucose infusion on the response to intravenous insulin was examined. Intracarotid glucose infusion rates were chosen to yield central euglycemia in the face of systemic hypoglycemia. Protocol 3: as a control for protocol 2, glucose was infused at low rates into the systemic circulation, yielding hypoglycemia in both central and systemic blood. When insulin was infused at 150 mU/min, without glucose replacement (protocol 1; N = 6), plasma insulin increased from 14 +/- 3 to 335 +/- 35 microU/ml at 60 min (P less than 0.001). Glucose fell from basal (104 +/- 3 mg/dl) to 38 +/- 3 mg/dl (P less than 0.001). Significant increases were observed in epinephrine (basal, B: 63 +/- 8; steady state, SS: 1762 +/- 582 pg/ml; P less than 0.007), norepinephrine (B: 209 +/- 33, SS: 650 +/- 133 pg/ml; P less than 0.01), and glucagon (B: 256 +/- 35, SS: 467 +/- 35 pg/ml; P less than 0.03). In addition, endogenous glucose production (Ra) increased from 72 +/- 4 to 108 +/- 9 mg/min (P less than 0.02) despite frank hyperinsulinemia. Infusion glucose into the carotid arteries at 204 +/- 10 mg/min (protocol 2; N = 7) during a 4-h systemic insulin infusion was sufficient to prevent jugular hypoglycemia [jugular glucose, Gj, B: 100 +/- 3, SS (90-160 min): 101 +/- 3 mg/dl; P greater than 0.70], but not peripheral hypoglycemia (Gp, B: 102 +/- 2, SS: 55 +/- 3 mg/dl; P less than 0.001). Despite carotid glucose replacement, counterregulatory responses were still observed in epinephrine (B: 98 +/- 14, SS: 466 +/- 127 pg/ml; P less than 0.04) and norepinephrine (B: 213 +/- 19, SS: 474 +/- 133 pg/ml; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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