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Biomedical subjects

B Carr

Publications and source records attributed to B Carr.

At least 19 recordsLinked to original sources

Residential summer camp for children with end-stage renal disease.

Residential summer camps exist for children with all varieties of chronic illness with the goal of improving their quality of life. This paper describes the development and implementation of a summer camp for children 9-18 years old who receive long-term peritoneal dialysis or who have received a kidney transplant. Thirty-five to forty children regularly participate in activities such as water olympics, survival hikes and campouts while continuing to receive their medical needs from trained personnel. A study to evaluate the impact of a summer camp revealed less patient hopelessness and improved self-esteem following the 1-week camping experience. Attendance at camp provided the medical staff with a unique perspective of childhood illness, while the period of respite for the parents was uniformly welcomed and may contribute to the prevention of parent burnout. It is hoped that the success of this camp and others like it will lead to the development of similar experiences for other children with chronic disease.

Adolescent

Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation.

The growth rates of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLTX) were estimated by calculating the tumor doubling time (TDT) in 20 patients. The mean TDT, calculated by multiple measurement of tumor size, was 44.3 +/- 11.3 days (mean +/- standard error) in 12 patients with pulmonary metastasis (range, 10 to 161 days) and 37.6 +/- 8.9 days (range, 7 to 65 days) in 5 patients with liver allograft recurrence. The TDT as estimated by serum alpha-fetoprotein (AFP) levels in 6 patients was 37.3 +/- 10.0 days (range, 12 to 84 days). The mean TDT obtained from 5 control subjects with HCC who were treated with liver resection (without immunosuppression) was 273.8 +/- 79.1 days (range, 82 to 560 days). The disease-free period and survival time after OLTX both correlated well with the TDT (r = 0.546 and r = 0.701, respectively). The patients with fibrolamellar HCC had a greater TDT and a longer survival time than those with nonfibrolamellar HCC. Despite a wide range of TDT in patients who received transplants, their recurrent HCC tumors grew significantly faster than those of patients with the same disease who did not receive transplants. The factors involved in this accelerated growth rate may include the use of immunosuppressive drugs and the consequent suppression of host immunity against the growth of micrometastasis.

Carcinoma, Hepatocellular

Prospective hospital study of community acquired lower respiratory tract infection in the elderly.

A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital.

Aged

Hepatic resection versus transplantation for hepatocellular carcinoma.

During the 10-year period (1980 to 1989), 76 patients with hepatocellular carcinoma (HCC) were treated by subtotal hepatic resection (HX) and 105 patients by orthotopic liver transplantation (TX) under cyclosporine-steroid therapy. Overall 1- to 5-year survival rates of the HX group were 71.1%, 55.0%, 47.2%, 37.2%, and 32.9%, respectively, and those of the TX group were 65.7%, 49.0%, 39.2%, 35.6%, and 35.6%, respectively. The survival rates after HX and after TX correlated well with pTNM stages and were similar in each stage between the two groups. However, when HCC was associated with cirrhosis of the liver, the survival rates after TX were significantly better than those after HX at each stage of pTNM classification. The tumor-recurrence rate was high both after HX (50%) and TX (43%), particularly in advanced stages of pTNM classification (60% or more). Twelve patients after HX and 13 patients after TX lived more than 5 years during this 10-year period. Fibrolamellar HCC and early stages of HCC were highly represented among the long-term survivors. Further improvement in survival rates depends on nonsurgical anti-cancer therapy before and/or after surgical removal of HCC.

Adolescent

Cardioversion of atrial fibrillation of recent onset with flecainide.

Twenty-eight patients with atrial fibrillation of less than 1 month's duration were given a single intravenous bolus of flecainide (2 mg/kg). Nineteen patients (68%) were successfully converted to sinus rhythm. Of the 19 patients with atrial fibrillation of less than 72 hours duration, 18 (95%) were successfully converted. Failure to cardiovert was associated with cardiomegaly on chest X-ray and larger left atrial diameter measured echocardiographically. Of the 9 patients who failed to convert, 2 had biochemical evidence of thyrotoxicosis and chronic obstructive pulmonary disease. Of the 19 patients successfully cardioverted, the atrial fibrillation complicated acute myocardial infarction in 3 cases and a pulmonary embolism in one. Six cases occurred post-operatively and in 3 out of 6 the patient was ventilated. No side effects were observed. The use of intravenous flecainide should avoid the need for electrical DC conversion even in sick patients. Failure of conversion is associated with covert underlying predisposing factors and duration of atrial fibrillation of more than 72 hours.

Adult

Abnormal prothrombin (DES-gamma-carboxy prothrombin) in hepatocellular carcinoma.

Des-gamma-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured by an enzyme immunoassay (E-1023) using anti-DCP monoclonal antibody in 92 patients with various hepatobiliary diseases. Thirty-six of the 38 patients (94.7%) with hepatocellular carcinoma (HCC) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml, but only 18 of the 35 patients (51.4%) had AFP greater than 100 ng/ml (suspicious levels for HCC). There was no correlation between plasma or serum DCP and serum alpha-fetoprotein (AFP) levels. Serum alpha fetoprotein was elevated (above 20 ng/ml) in 23 of the 35 patients (65.7%), and DCP was elevated in all of the remaining 12 patients with normal AFP. DCP levels returned to normal levels following curative hepatic resection or orthotopic liver transplantation for HCC. DCP is a useful tumor marker in the diagnosis and postoperative monitoring of patients with HCC.

Biomarkers

Liver transplantation for alcoholic liver disease, viral hepatitis, and hepatic neoplasms.

In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care.

Adult

Treatment of metastatic malignant melanoma with trimetrexate: a phase II study.

Trimetrexate glucuronate, a nonclassical antifolate, was administered to 14 patients with recurrent and progressive metastatic malignant melanoma. Thirteen patients were evaluable for response and toxicity. Five patients had received prior treatment consisting of immunotherapy (one patient), immunotherapy plus radiotherapy (one patient), radiotherapy (one patient), chemotherapy (one patient), or radiotherapy and chemotherapy (one patient). The starting dose of trimetrexate was 8 mg/m2 given as an intravenous bolus daily for 5 consecutive days of a 21-day cycle. Subsequent cycles of therapy were escalated by 25% based on individual patient tolerance. A median of two courses of trimetrexate was administered (range 1-4). No patient demonstrated a measurable objective response to this treatment regimen. Trimetrexate was well-tolerated; toxicity was mild and consisted primarily of myelosuppression or nausea and vomiting. At the dose level and schedule used in this study, trimetrexate was not effective for the treatment of disseminated malignant melanoma.

Adult

3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.

Adult

A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm.

Cryopreserved sperm have lowered fertility when compared with fresh sperm in artificial insemination by donor programs. The purpose of this study was to compare pregnancy rates following intrauterine insemination (IUI) and intracervical insemination (ICI) with cryopreserved sperm in a prospective trial using the patient as her own control. A total of 154 patients were randomized into alternating treatment cycles and underwent 238 cycles of IUI and 229 cycles of ICI. The pregnancy rate per treatment cycle was 9.7% following IUI and 3.9% following ICI. Treatment outcome was influenced by patient age, ovulatory status, and endometriosis. Pregnancy success correlated well with the post-thaw survival of sperm and the number of motile cells inseminated. In spite of having normal semen parameters, some donors were found to have markedly reduced sperm fecundity. We conclude that IUI with cryopreserved sperm can be an effective treatment for couples with infertility, genetic indications, or other reasons.

Adult

Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy.

Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

Adenocarcinoma

Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration.

Heparin-binding growth factor type 1 (HBGF-1; sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. HBGF-1 alone (half-maximal effect at 60 pM) stimulated hepatocyte DNA synthesis and bound to a high-affinity receptor (Kd = 62 pM; 5000 per cell). Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. HBGF-1 reduced the inhibitory effect of transforming growth factor type beta (TGF-beta) on the EGF stimulus. Nanomolar levels of HBGF-1 decreased the EGF stimulus. An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-alpha, and nonparenchymal-cell-derived TGF-beta in the regenerating liver. Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-alpha stimulus. It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-beta. An EGF/TGF-alpha-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-beta may serve to limit hepatocyte proliferation.

Animals