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Biomedical subjects

H Anderson

Publications and source records attributed to H Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode.

OBJECTIVES: This study was designed to analyze the incidence and determinants of complications and long-term survival in sinus node disease treated with atrial pacing. BACKGROUND: Knowledge of the natural history of sinus node disease treated with different pacing modes is imperfect, and controversy exists regarding the optimal pacemaker therapy. METHODS: A consecutive series of 213 patients with sinus node disease initially treated with atrial pacing was studied for a median follow-up period of 60 months. The end points studied were permanent atrial fibrillation, high grade atrioventricular (AV) block, P wave undersensing, pacing mode change, reoperation and death. Several prognostic factors were evaluated statistically and the survival rate was compared with that of a matched general population. RESULTS: The incidence rate of permanent atrial fibrillation during follow-up was 7% (1.4%/year). The risk of this arrhythmia increased substantially with age greater than or equal to 70 years at pacemaker implantation. Only 2 of the 15 patients who developed permanent atrial fibrillation required ventricular pacing. High grade AV block occurred in 8.5% (1.8%/year) and its incidence was much greater in patients with complete bundle branch block or bifascicular block (35%) than in patients without such conduction disturbances (6%). A change to ventricular or dual-chamber stimulation was necessary in 14% of all patients, primarily because of early lead dislodgment or high grade AV block. Surgical intervention with maintenance of atrial pacing was required in 7% of patients. The survival rates of 97% at 1 year, 89% at 5 years and 72% at 10 years did not differ significantly from those of a matched general population. CONCLUSIONS: In sinus node disease, atrial pacing can be successfully applied during long-term follow-up. Patients with complete bundle branch or bifascicular block in addition to sinus node disease should initially receive a dual-chamber pacemaker, but routine application of dual-chamber stimulation does not appear to be warranted.

Adolescent↗
PubMed1992

Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor.

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis.

The incidence and risk of septic complications in 382 patients treated for small cell lung cancer with combination chemotherapy at a single centre have been analysed. Full protocol doses were employed throughout with no dose reduction after episodes of severe or life-threatening sepsis (SLTS). 50 (13%) patients experienced 66 episodes of SLTS associated with 1978 cycles of chemotherapy (3.2% cycles affected). 20 (5.2%) patients died due to sepsis (SD) of whom only 4 had experienced SLTS with a previous cycle of treatment. The others died as a result of their first septic episode. A model comprising four variables, age (< or = 50 or > 50 years), Karnofsky performance status (KP < or = 50 or > 50), treatment (two- or three-drug regimen) and previous sepsis (SLTS or no SLTS with previous cycles) was found to satisfactorily describe the incidence of SLTS and SD in the study population and once validated in another patient groups this model should allow identification of high-risk individuals before treatment starts. If so, we propose that high-risk patients (age > 50 years, KP < or = 50, treatment with three-drug regimen) receive 50% of protocol doses in the first cycle of treatment with escalation to 75% and eventually 100% doses in subsequent cycles if sepsis does not supervene. Those with one or two risk factors present run a relatively low risk of SLTS or SD and we consider that full-dose chemotherapy should be used throughout in these individuals.

Age Factors↗
PubMed1992

Chromosome abnormalities are associated with unfavorable outcome in prostatic cancer patients.

Potential clinico-cytogenetic correlations were assessed in 57 patients with prostatic cancer in whom cytogenetic analysis of the primary tumor had been successful. Clonal karyotypic abnormalities were found in 15 tumours, 18 had normal karyotypes with nonclonal structural abnormalities and 24 had normal karyotypes only. The study began in January 1987 and all patients were monitored regularly until death or through September 1990 (median followup from diagnosis 2.6 years and from surgery 1.3 years). Survival curves were estimated by the Kaplan-Meier method, and the log rank test was used in univariate analyses of possible prognostic factors. The patients with clonal karyotypic abnormalities had shorter survival times (1.3 years) than those with normal karyotypes (greater than 3 years). The difference in survival after surgery was statistically significant (p less than 0.05) when all causes of death and when death from prostatic cancer alone were considered. The Cox proportional hazards regression model was used to evaluate the additional prognostic information of chromosomal changes in excess of that attributable to other well known prognostic factors, such as tumor stage and differentiation, acid and alkaline phosphatases, and performance status. In this analysis there also was a tendency for patients with clonal chromosome aberrations to have an unfavorable outcome but the association was not significantly (p = 0.13), possibly due to the rather small number of patients and short followup. Thus, our study suggests that the presence of clonal karyotypic changes in the tumor cells is associated with an unfavorable outcome in prostatic cancer patients.

Adenocarcinoma↗
PubMed1992

Response after withdrawal of tamoxifen and progestogens in advanced breast cancer.

Tumor response after withdrawal of endocrine therapy for advanced breast cancer with estrogens and androgens is well described. There have been few reports of withdrawal responses (WRs) after cessation of treatment with the newer antiestrogens and progestogens. We assessed WR in women after cessation of adjuvant therapy at first relapse, and after progression on first, second or third line endocrine therapy for advanced disease. One of seven patients (14%) responded after cessation of tamoxifen adjuvant therapy at relapse. Sixty-five of 72 patients were evaluable for WR after cessation of tamoxifen as first line therapy for advanced disease. There were five partial responses (8%) and 14 (22%) 'no change' with a median duration of WR of 10 months (range 3-40 months). WR were seen mainly in soft tissue disease but there were two responses in lung and two in bone. Four of 21 (19%) patients had a WR after cessation of norethisterone acetate (3) and tamoxifen (1), all used as second line therapy. WR are therefore demonstrable after cessation of tamoxifen and norethisterone acetate with durations of response similar to those found with additive therapy. Assessment of WR may represent a way of prolonging the overall response duration in patients with relatively indolent metastatic breast cancer, particularly in soft tissues.

Adult↗
PubMed1992

2-Mercaptoethanol influences the in vitro function of bovine peripheral blood mononuclear cells.

The effects of 2-mercaptoethanol (2-ME) on some in vitro functions of bovine peripheral blood mononuclear cells (PBMC) were examined. It was shown that 2-ME enhanced, in a dose-dependent manner, the production of antibodies to bovine coronavirus. In this test the optimal concentration of 2-ME was 50 microM. This molarity of 2-ME was also optimal for the pokeweed mitogen (PWM)-induced proliferation of PBMC obtained from the 7 cattle tested. Similarly, the spontaneous proliferation of PBMC from 4 out of these cattle was enhanced. Thus, 2-ME evoked an increase (up to 2.5 times) or a decrease (at most 10 times) of the quota between the PWM-induced and the spontaneous proliferation (stimulation index). In general, the presence of 50 microM 2-ME enhanced the in vitro production of interferon by bovine PBMC. On the contrary, the highest proliferative response of PBMC to stimulation with bovine virus diarrhoea virus was achieved in cultures without 2-ME or in cultures with 0.5 or 5 microM 2-ME. Since the effects of 2-ME varied, for different tests as well as for cattle tested, attention should be paid to the use of 2-ME in cultures of bovine PBMC.

Animals↗
PubMed1992

Effects of amino acid dialysate on appetite in CAPD patients.

The use of amino acid (AA) dialysate in CAPD patients may have theoretical disadvantages, since protein ingestion is known to suppress food intake in humans disproportionately to its energy value. Therefore we measured subjective appetite and food intake of CAPD patients in a cross-over study of 16 subjects (age 22-75 years, BMI 19-31, > 3 months on CAPD, non-diabetic and not protein malnourished). They received, in random order, either 4 weeks of dextrose only (their usual treatment), or one AA (1%) exchange replacing the first dextrose exchange each day. Subjective measurements of food intake (3 day food record) and quantitative measurements of lunch time food intake were obtained during a morning dextrose exchange after 28 days of each regimen. Except for a reduction in feelings of fullness during the AA treatment, there were no effects on feelings of hunger/satiety, food appeal, lunch-time food intake, or on 3-day food intake. We conclude that the use of a daily AA (1%) dialysate for 4 weeks does not affect subjective appetite or food intake of CAPD patients. There may even be a beneficial effect as the feeling of fullness decreased with the AA treatment.

Adult↗
PubMed1991

A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4.

The authors undertook a controlled, prospective, randomized study of 171 patients with supratentorial astrocytoma grades 3 and/or 4 (classified according to Kernohan). All patients were given chemotherapy consisting of procarbazine, vincristine, and lomustine (CCNU) (PVC). Half of the patients received whole-brain irradiation (RT) to a dose of 5800 cGy in the tumor-bearing hemisphere and 5000 cGy in the contralateral hemisphere. After diagnosis of progressive tumor growth, patients received individual treatment. The endpoint of the study was time to progression, but cases were followed until the patients died. Median time to progression (MTP) for the whole randomized population was 21 weeks. Median survival time (MST) was 53 weeks; 18% of patients survived for 2 years or longer. Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP (81 weeks) and MST (124 weeks) than all other patients. For patients less than 50 years of age treated with PVC alone, MTP was 21 weeks and MST was 66 weeks. For patients more than 50 years of age treated with PVC plus RT, MTP was 23 weeks and MST was 51 weeks; in the PVC group, MTP was 17 weeks and MST was 39 weeks. Age, Karnofsky index, areas of Grade 2, and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses. Patients less than 50 years of age treated with PVC plus RT had significantly longer survival (P = 0.037) when correcting for these factors in a multi-variate analysis.

Adult↗
PubMed1991

A randomised study of adjuvant MVPP chemotherapy after mantle radiotherapy in pathologically staged IA-IIB Hodgkin's disease: 10-year follow-up.

One hundred fifteen untreated patients with supra-diaphragmatic, pathologically staged (PS) IA-IIB Hodgkin's disease (HD) were entered into a randomised study comparing treatment using mantle radiotherapy followed by adjuvant treatment with mustine, vinblastine, prednisolone, and procarbazine (MVPP) with mantle radiotherapy alone. Fifty-six patients were randomised to receive radiotherapy alone (RT) and 59 to radiotherapy followed by six cycles of adjuvant MVPP (RT + MVPP). One hundred fourteen patients achieved a complete remission (CR) with radiotherapy. One patient achieved a partial remission. The overall 10-year survival after correction for intercurrent death was 92% with no difference between the two treatment groups (90% for RT alone and 95% for RT + MVPP P = 0.66). There were 9 (8%) deaths from HD (5 patients had received RT alone), and 10 (9%) intercurrent deaths. Eight (7%) patients have developed a second malignancy, and two of them are alive. No patient has developed secondary acute myelogenous leukaemia. The 10-year relapse-free survival (RFS) was 79% overall, 67% in the RT group, and 91% in the RT + MVPP group (P = 0.0004). There were 25 relapses; 20 patients had received RT alone and 5 had received adjuvant MVPP. Of the relapsed patients, 13 (52%) have received successful salvage therapy and are in CR. In the RT alone group, 45 (80%) patients are alive in CR, 5 (9%) died of HD, and 6 (11%) died of intercurrent causes. In the adjuvant MVPP group, 51 (86%) are alive in CR, 4 (7%) died of HD, and 4 (7%) died of intercurrent causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Recombinant human GM-CSF in small cell lung cancer: a phase I/II study.

Seventeen patients with small cell lung cancer were entered into a dose ranging phase I-II study using rhGM-CSF (Glaxo). In the phase I study patients received 50, 150, 300 or 500 micrograms/m2 GM-CSF for 10 days by daily subcutaneous injection. Full blood counts were performed thrice weekly. After 4 days off all therapy patients then received chemotherapy with doxorubicin 50 mg/m2 i.v. bolus, day 1, ifosfamide 5 g/m2 with mesna 5 g/m2 over 24 h by continuous infusion followed by mesna 3 g/m2, and etoposide 120 mg/m2 i.v. on days 1-3. A total of six courses of chemotherapy were given. In the phase II study patients received the same dose of GM-CSF as in the phase I. GM-CSF was given 24 h after the last dose of chemotherapy for 14 days. Full blood counts were checked thrice weekly and the incidence of infections noted. Patients were randomised to receive GM-CSF with either odd or even courses of chemotherapy. The leucocyte count rose from a mean of 8.7 to 21.6 x 10(9)/l at the 50 micrograms/m2 GM-CSF dosage and from 11.4 to 39.4 x 10(9)/l at the 500 micrograms/m2 dosage during the phase I study. Phase I toxicity was: bone pain in 65% of patients, rash in 47%, fever in 24%, lethargy in 12% and diarrhoea in 12%. In the phase II study the duration of neutropenia was less during the chemotherapy courses with GM-CSF (p = 0.04) but the number of infections was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Polychlorinated biphenyl congeners in blood of Wisconsin sport fish consumers.

As part of a study to evaluate the effect of chemical contaminants on Wisconsin sport fish consumers, measurements were made of polychlorinated biphenyl (PCB) congeners in human blood sera. A high resolution gas chromatography procedure was employed, with 13 individual congeners used as standards. Analytical recoveries and precision were greater than 90% and replicates were always within +/- 30%. Total concentrations, obtained by summing quantified congeners, ranged from 0.6 to 27.1 micrograms/L. Conventional packed column PCB analysis, conducted on a subset of samples, gave higher total PCB results. On a congener specific basis, congeners 153 (245-245), 138 (234-245), 180 (2345-245) and 118 (245-34) were found most often. These congeners have been reported to be prominent in other matrices. Of the congeners found, 118, 138, and possibly 180 are potentially the most toxic (based on current toxicological information).

Animals↗
PubMed1991

A randomised study of intravenous bolus versus continuous infusion of ifosfamide and doxorubicin with oral etoposide for small-cell lung cancer.

159 "poor risk" patients with previously untreated small cell lung cancer were entered into a randomised study of intravenous bolus versus continuous infusion chemotherapy with doxorubicin on weeks 1, 3, 5 and ifosfamide with mesna on weeks 2, 4, 6. Oral etoposide was given on days 1-5, 15-19, and 29-33. There was no difference in response rate or survival. However, patients treated with continuous infusion therapy had significantly less haematological toxicity (P = 0.0007), and less nausea and vomiting (P = 0.03).

Administration, Oral↗
PubMed1991

MMAF for advanced gastric cancer.

65 patients with metastatic gastric carcinoma were treated with a combination of methotrexate 1.5 g/m2 with 5-fluorouracil 1.5 g/m2 on day 1 and doxorubicin 30 mg/m2 with mitomycin 4 mg/m2 on day 14. Cycles of chemotherapy were repeated every 4 weeks. The overall response rate was 29% with 6% complete responses and 23% partial responses. Prognostic factors that individually affected response were Karnofsky performance (P less than 0.002), and site of the primary tumour (P less than 0.007). Multivariate analysis showed that only increasing Karnofsky performance (P = 0.01) and disease status (P less than 0.02) (patients with recurrent tumours responding better than patients with postoperative residual disease and those with inoperable disease) were important in predicting response to therapy. The overall median survival was 7 months. All 4 patients with a complete response are alive in remission at 13, 28, 48 and 52 months from the date of starting chemotherapy. Univariate analysis identified increasing Karnofsky performance (P less than 0.0001), response to chemotherapy (P less than 0.02) and higher serum albumin (P less than 0.03) as prognostic indicators for survival. Multivariate analysis, of pretreatment factors and day 14 full blood count showed that only Karnofsky performance (P less than 0.0001) and day 14 platelet count (P less than 0.03) were shown to predict survival, higher platelet values being associated with decreased survival.

Adenocarcinoma↗
PubMed1991

Phase II study with mitomycin, ifosfamide and carboplatin in inoperable non-small cell lung cancer.

In a phase II study of non-small cell lung cancer a new chemotherapy combination of mitomycin 6 mg/m2 intravenously on day 1, carboplatin 400 mg/m2 intravenously on day 1 and ifosfamide with mesna 5 g/m2 intravenously over 24 hours on day 1 was evaluated. A maximum of four chemotherapy cycles was given at intervals of 4 weeks to 34 patients with progressive, inoperable disease. 1 complete and 10 partial remissions were documented, the overall response rate being 32.4%. In a further 13 patients (38.2%) the previously progressing tumours remained stable for at least 6 weeks. The median time to progression for responding patients was 184 days. The median survival time for the whole group has not yet been reached at 293 days. A considerable but easily manageable myelosuppression was the principal toxicity despite a "no dose reduction" policy. Indeed, the dose intensity of the chemotherapy actually given was extremely close (97%) to that intended on protocol. In conclusion, the regimen is active in patients with advanced non-small cell lung cancer but requires regular haematological monitoring to prevent morbidity resulting from myelotoxicity.

Aged↗