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Biomedical subjects

G Farr

Publications and source records attributed to G Farr.

At least 19 recordsLinked to original sources

Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group.

Hepatitis B after liver transplantation is often fatal, and no proven medical therapy exists for this condition. We chose to study the potential efficacy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty-two patients with chronic hepatitis B after liver transplantation were treated in an open label, multicenter study. Each had detectable hepatitis B virus (HBV) DNA in serum and 45 (87%) had detectable serum hepatitis B e antigen before treatment. Patients were treated for 52 weeks with lamivudine (100 mg daily). The primary endpoint was undetectability of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and improvement in liver histology. After treatment, 60% of patients had undetectable HBV DNA by solution hybridization assay, 14 (31%) of the initially positive patients lost hepatitis B e antigen; hepatitis B surface antigen was undetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded histological assessments showed improvement in the histological activity index (P =.007 for periportal necrosis,.001 for lobular necrosis, and.013 for portal inflammation). YMDD variants of HBV, potentially associated with drug resistance, were detected in 14 (27%) of the patients. Repeat liver biopsies in 7 patients with the mutated virus were unchanged in 2, improved in 2, and worse in 3. We conclude that lamivudine is a potentially effective therapy for hepatitis B after liver transplantation.

Adult

Hepatic manifestations of familial patent ductus venosus in adults.

BACKGROUND: The ductus venosus connects the umbilical vein to the inferior vena cava during fetal life and subsequently closes rapidly after birth. It is known as patent ductus venosus when it remains patent in adulthood. PATIENTS: A 43 year old man with a history of panhypopituitarism presented with recurrent bouts of pedal oedema associated with fatigue, hypoalbuminaemia, and elevated prothrombin time. An ultrasound examination of his abdomen with Doppler revealed notable attenuation of the main portal vein with diminished intrahepatic branches; a computed tomography scan with angiography revealed a large collateral vein within the liver consistent with a patent ductus venosus. Sequential liver biopsies showed a considerable reduction in the calibre and number of the portal veins. His younger brother, who was diagnosed with alcohol related cirrhosis, suffered from intermittent bouts of encephalopathy and was found to have the same vascular lesion. A third brother was found to have a patent ductus venosus as well as two large hepatic masses consistent with focal nodular hyperplasia. CONCLUSION: The syndrome of familial patent ductus venosus has only previously been described in three infant brothers who presented with hepatic encephalopathy and fatty degeneration of the liver. This report documents three brothers with a patent ductus venosus presenting in adulthood with different manifestations of liver disease. The presence of the same vascular anomaly in three brothers is highly suggestive of a recessive genetic trait with an anatomical manifestation of patent ductus venosus.

Adult

Twelve-month comparative multicenter study of the TCu 380A and ML 250 intrauterine devices in Bangkok, Thailand.

The long-term effectiveness of the copper-bearing intrauterine device (IUD) has been documented. This paper reports 12-month results from a multiyear comparative study of the Copper T (TCu) 380A and Multiload (ML) 250 IUD in Bangkok, Thailand, among 1396 women. Continuation of the assigned IUD was relatively high after 12 months of use, with continuation rates of 90.17 and 87.54 per 100 women, respectively. Whereas the accidental pregnancy rate was higher for the ML 250 IUD than for the TCu 380A IUD (1.0 and 0.2 per 100 women, respectively), this difference was not considered statistically significant (p < 0.69). The rate of IUD expulsion was significantly higher among women using the ML 250 IUD than for women using the TCu 380A IUD (4.61 and 2.40 per 100 women, respectively, p = 0.05).

Adult

Non-physician insertion of IUDs: clinical outcomes among TCu380A insertions in three developing-country clinics.

Insertion of IUDs by trained non-physicians is increasing. This secondary analysis of TCu380A IUD acceptors collected at clinics in Nigeria, Turkey and Mexico involved 367 women; 193 insertions were performed by physicians and 174 by non-physicians. Women having their IUD inserted by a non-physician were more likely to experience a pain-free insertion, but also likelier to have the IUD removed for bleeding and pain or to experience an expulsion than women who had their IUD inserted by a physician. Early discontinuation rates were similar between the two groups. Overall continuation rates were statistically higher for IUDs inserted by physicians only at the Mexico site. Trained non-physicians can probably safely insert the TCu380A IUD. Appropriate competency-based training is required to limit the number of expulsions and removals for bleeding and pain by non-physicians.

Adult

Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results.

OBJECT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. METHODS: The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. CONCLUSIONS: The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.

Adult

Safety, functionality and acceptability of a prototype polyurethane condom.

Male condoms made from synthetic materials offer an alternative to latex condoms that may be more acceptable to users, thereby potentially resulting in more protected acts of intercourse. A prospective, noncomparative clinical study was conducted to evaluate the safety of using certain polyurethane materials to make condoms. Fifty-one healthy, contracepting, mutually monogamous couples were recruited between June 30 and November 24, 1993 to use a prototype roll-on polyurethane condom developed by Family Health International. Couples were to use the condoms for 10 consecutive acts of vaginal intercourse over a 4-week period. Baseline and postexposure genital examinations, including colposcopy for female participants, were performed. Fifty couples completed the study requirements and 517 acts of intercourse occurred using the condoms. Two adverse events were reported: irritation of introitus in a female participant and a small irritated erythematous lesion on a male participant's penis. Neither event was considered to be serious and both were resolved without treatment. Breakage and slippage rates were similar to those reported for latex condoms. These results suggest that polyurethane condoms represent a safe, functional and acceptable alternative to latex condoms.

Adult

Tissue factor pathway inhibitor protects the ischemic spinal cord.

Tissue factor pathway inhibitor (TFPI) is a novel agent that binds to tissue factor/VIIa complex and factor-Xa, thereby reducing the effect of tissue factor (TF) on inflammation and the extrinsic pathway of coagulation. We hypothesize that systemic treatment with TFPI may limit ischemia-reperfusion (IR) injury. Our experiment was designed to evaluate the effects of TFPI on IR in the spinal cord. Twenty-three adult New Zealand white rabbits had snare occlusion devices placed circumferentially around the aorta and tunneled to a subcutaneous position. Forty-eight hours later, in the fully awake state, the animals were treated with either TFPI (1 mg/kg bolus followed by a 1-hr infusion of 20 microgram/kg/min), or heparin (100 U/kg bolus) followed by a 1-hr infusion of 10 ml/kg/hr of PBS while controls received phosphate buffered saline (20 ml followed by a 1-hr infusion of 10 ml/kg/hr). The infrarenal aorta was occluded for 21 min in all groups via the snare device. Animals were observed for 3 days and neurologic recovery was graded by the Tarlov criteria. Results were evaluated as percent of animals with hindlimb recovery (Tarlov 3 and 4). At 24 hr postocclusion, 88% of the TFPI-treated animals had recovered neurologic function versus only 20% of heparin-treated animals and 10% of the phosphate buffered saline group (P=0.031 and 0.009, respectively). At 72 hr, 63% of the TFPI animals retained neurologic function versus 20% of heparin-treated animals and 10% of phosphate buffered saline-treated animals (P=0.032, TFPI versus phosphate buffered saline). The mechanism of action of TFPI is not completely understood, yet this drug may hold promise in the prevention of IR injury of the spinal cord.

Animals

Liver transplantation for hepatocellular carcinoma: one center's experience, 1987-1994.

A retrospective review was done to evaluate the detection of hepatocellular carcinoma preoperatively, using ultrasonography and alpha-fetoprotein in patients awaiting orthotopic liver transplantation. Sixteen of the 187 patients who underwent 209 orthotopic liver transplantations at the Ochsner Transplant Center from 1987 to 1994 were diagnosed with hepatocellular carcinoma, 3 preoperatively and 11 at the time of pathological inspection of the liver explant. Two developed metastatic hepatocellular carcinoma while awaiting orthotopic liver transplantation. Ultrasonography detected abnormalities in the region where hepatoma was identified in 5 of 11 (45%) patients with incidental hepatocellular carcinoma, in all 3 with overt hepatocellular carcinoma, and in neither of the 2 who developed metastatic hepatocellular carcinoma while awaiting orthotopic liver transplantation. Hepatocellular carcinoma was present in 5 of 23 (22%) patients with an alpha-fetoprotein greater than 20 ng/mL and in 3 of 10 (30%) with an alpha-fetoprotein greater than 50 ng/mL.

Carcinoma, Hepatocellular

Prolonged survival in fibrosing cholestatic hepatitis with long-term ganciclovir therapy.

A 45-yr-old man underwent liver transplantation for cirrhosis due to hepatitis B and developed recurrent infection. Serial liver biopsies revealed fibrosing cholestatic hepatitis, an entity that is associated with rapid graft failure, and this was treated with long-term intravenous ganciclovir therapy. The patient is alive and well 2 yr after transplantation, despite the presence of well-established cirrhosis and a marked accumulation of intrahepatic hepatitis B surface and core antigens. It is postulated that partial reduction of viral replication resulted in an incomplete syndrome in which rapid graft failure did not occur, but progressive fibrosis developed. Our case suggests that newer nucleoside analogues that provide a greater degree of inhibition to hepatitis B virus replication may greatly improve the outcome of patients with recurrent infection after liver transplantation.

Antiviral Agents

An evaluation of the copper-T 380A IUD's safety and efficacy at three African centers.

The use of intrauterine devices in Africa is low compared with other contraceptive methods such as oral contraceptives. This study, coordinated by Family Health International, evaluated the clinical performance (safety and efficacy) of the TCu 380A IUD in three African centers, respectively, in Cameroon, Egypt, and Nigeria from 1986-1989. The 12-month unintended pregnancy rates were low for all three centers, ranging from none to 1.6 per 100 women. The 12-month discontinuation rates for all reasons ranged from 8.8 to 26.9 per 100 women. Statistically significant differences were observed among clinics for discontinuation rates for bleeding and/or pain and for planned pregnancy. The overall performance of the TCu 380A IUDs was considered satisfactory. Thus, the limited use of IUD in Africa could be due to the lack of accessibility, lack of information about, and confidence in the method rather than to documented clinical performance.

Cameroon

Stereotactic core needle breast biopsy is an accurate diagnostic technique to assess nonpalpable mammographic abnormalities.

The minimally invasive technique of stereotactic core needle breast biopsy threatens to replace surgical excisional biopsy as the preferred method to diagnose most mammographic abnormalities. The goal of this study is to evaluate the ability of stereotactic core needle breast biopsy to accurately assess suspicious nonpalpable masses and calcifications on mammography. A prospective protocol was initiated which called for stereotactic core needle breast biopsy instead of traditional excisional biopsy to assess suspicious calcifications and masses noted on mammography. A minimum of five core biopsies are excised by a radiologist, histologic evaluation is performed by the department of pathology, and clinical correlation between the radiographic and pathologic findings is assessed by the surgeon. Malignant lesions are appropriately treated and clearly benign lesions are followed mammographically. During the initial 18 months after the protocol was activated, 451 patients were evaluated by stereotactic core needle breast biopsy. There were 367 benign cases documented by stereotactic core needle breast biopsy and 84 malignant cases. One benign stereotactic core needle breast biopsy case proved to be malignant at subsequent surgical biopsy and one malignant stereotactic core needle breast biopsy case could not be confirmed at subsequent surgical biopsy. The results of this study demonstrate that stereotactic core needle breast biopsy provides accurate histologic evaluation of mammographic abnormalities. A multidisciplinary approach to include radiologist, pathologist, and surgeon is critical to ensure a thorough and accurate assessment of nonpalpable breast lesions.

Biopsy, Needle

A homeobox gene essential for zebrafish notochord development.

The notochord is a midline mesodermal structure with an essential patterning function in all vertebrate embryos. Zebrafish floating head (flh) mutants lack a notochord, but develop with prechordal plate and other mesodermal derivatives, indicating that flh functions specifically in notochord development. We show that floating head is the zebrafish homologue of Xnot, a homeobox gene expressed in the amphibian organizer and notochord. We propose that flh regulates notochord precursor cell fate.

Amino Acid Sequence

Effectiveness of the non-spermicidal fit-free diaphragm.

Standard instructions for diaphragm use call for an individually sized latex diaphragm, used in conjunction with spermicide jelly. However, some investigators have reported that the diaphragm can be effective without a spermicide. A non-randomized trial designed to measure the contraceptive effectiveness of the diaphragm used without spermicide was conducted. A total of 110 self-selected women were enrolled to use a non-spermicide fit-free (60mm) diaphragm for a period of one year. They were advised to wear the diaphragm continuously, removing it once each day for washing but not within six hours after intercourse. Product-related problems related to insertion, retention and removal were few at both the 6- and 12-month follow-up visits, most commonly odor. The 12-month life table accidental pregnancy rate during typical use was 24.1 per 100 women (29.5 per 100 women without female barrier experience and 17.9 per 100 women with barrier experience). Over 85% of the women who returned for follow-up visits reported using the diaphragm during every act of intercourse. Until better data refute the traditional recommendations, users should be advised to add spermicide to fitted latex diaphragms.

Adult

Clinical performance of the TCu 380A and Lippes Loop IUDs in three developing countries.

The clinical performance of the Copper T 380A (TCu 380A) and the Lippes Loop intrauterine devices (IUDs) were evaluated for 12 months in a group of 710 women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at three collaborating research sites located in three developing countries. The gross cumulative life-table pregnancy rate of the TCu 380A IUD was found to be lower than that of the Lippes Loop IUD at 12 months (0.7 and 2.1 per women, respectively). Although this difference was not statistically significant (p = 0.25), it is similar to findings from other studies. The 12-month cumulative removal rate due to personal reasons was significantly different (1.4 and 0.0, respectively, p = 0.05). Statistically significant differences between the two study IUDs were not found with regard to IUD expulsion or IUD removal due to bleeding/pain, medical reasons, planned pregnancy or investigator's choice. A statistically significant difference (p = 0.03) was observed in the number of TCu 380A IUD users experiencing dysmenorrhea (26.1%) during the 12-month study period, compared to Lippes Loop IUD users (18.8%).

Adolescent

Contraceptive efficacy of the Copper T380A and the Multiload Cu250 IUD in three developing countries.

The clinical performance of the Copper T380A (TCu380A) and the Multiload 250 (MLCu250) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in three developing countries. The gross cumulative life-table pregnancy rate of the TCu380A IUD was significantly lower than the rate with the MLCu250 IUD at 12 months (0.5 and 1.2, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. TCu380A IUD users were more likely to report experiencing increased dysmenorrhea (p < 0.01) or intermenstrual pelvic pain (p < 0.01) than were MLCu250 IUD users. However, few of these users discontinued use of their assigned IUD because of having experienced menstrual bleeding disturbances or intermenstrual pelvic pain. These data indicate that the TCu380A IUD may be a better option than the MLCu250 IUD for women wishing to practice highly effective long-term birth control without having to resort to hormonal methods.

Adult

The non-contraceptive effects of the levonorgestrel-releasing intrauterine device.

Clinical trials have consistently shown that the IUD that releases 20 micrograms levonorgestrel daily (LNG-IUD-20) has a contraceptive efficacy comparable to, if not surpassing, the Copper T380 and the Multiload Copper-375 IUDs. The focus of this review is the device's non-contraceptive effects--the beneficial ones, such as reduction of menorrhagia, a therapeutic effect on dysmenorrhea, and prevention of ectopic pregnancy, as well as the deleterious ones, such as amenorrhea, spotting and irregular bleeding, hormonal side-effects, and functional ovarian cysts. Also discussed are the possibility of a preventive effect on pelvic inflammatory disease, the effects of the IUD on postpartum/lactating women, fertility return after removal and other safety issues. In general, the LNG-IUD-20's non-contraceptive benefits are substantive, carry important medical and public health implications, and far outweigh the device's deleterious effects, which are either medically mild or transient in nature, and can usually be managed satisfactorily by counseling. A better understanding of these effects, both beneficial and deleterious, of this hormone-releasing IUD should lead to more effective patient counseling, which, in turn, should improve user quality of life, minimize unnecessary removals, and maximize continuation of use.

Female

An analysis of the personal reasons for discontinuing IUD use.

The objective of this study was to evaluate possible factors associated with discontinuing use of TCu 380A IUDs due to personal reasons among 2748 users. Overall, a total of 88 subjects discontinued using the TCu 380A IUD within 12 months postinsertion for personal reasons. The most common reasons were planned pregnancy (32%) and husband or family opinion against IUD use (26%). The gross cumulative 12-month life table discontinuation rate for all personal reasons was 4.0 per 100 women. Having no education and/or living in a rural area were the sociodemographic characteristics associated with an increased risk of discontinuation for personal reasons. Effective and regular counseling about IUD use, especially among illiterate women, may help prevent IUD discontinuations related to personal reasons.

Attitude