Heterogeneity of tumour necrosis factor production in renal cell carcinoma.

Endogenous tumour necrosis factor (TNF) production was investigated by in situ hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients at different stages of disease. Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression. Two metastatic tumours investigated showed abundant TNF protein production and marked macrophage infiltration. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Two years after nephrectomy the individual survival time was recorded; however, the small numbers did not yet allow any correlation of TNF production to the clinical course of disease. Further studies will be required to eventually reveal the role of TNF in renal cell carcinoma development.


Early assessment of a new anticancer drug analogue--are the historical comparisons obsolete? The French experience with pirarubicin.

Data of all phase II studies of pirarubicin (THP-doxorubicin) have been analysed for toxicity or activity in breast cancer and compared with published reports on doxorubicin, epirubicin or mitoxantrone used as single drugs. A graph of the 95% confidence intervals for each event was used. The results suggest that pirarubicin is as effective as other intercalating drugs in breast cancer and grossly better tolerated than doxorubicin, especially alopecia and cumulative cardiotoxicity. The equimyelotoxic doses of each drug were also estimated. The methodology and the validity of such historical comparisons is discussed: they cannot replace prospective randomised phase III studies, and do not allow definitive conclusions. However, most comparative trials of anticancer drug analogues cannot answer the right questions because their objectives are not adequate (especially for equiefficacy). But early evaluation by historical comparisons can help the conception of phase III studies.


Prognostic value of progesterone receptor after long-term follow-up in primary breast cancer.

In a previous study of a series of 105 patients with primary breast cancer we found that the progesterone receptor (PgR) status was an important prognostic factor for early recurrences. 95 patients from the same series were followed-up for a median of 9.5 years and reassessed for the prognostic value of PgR status by univariate and multivariate statistical methods. In univariate analysis, the disease-free interval was only related to the lymph-node status. For overall survival, PgR and combined PgR-ER (oestradiol receptor) status had a prognostic value (P = 0.035 and 0.05, respectively). Moreover, PgR status was found to be discriminant for the survival of the node-negative patients (P = 0.017). In multivariate analysis, ER and PgR status were not significant, indicating that receptor status is not a powerful predictor of the course of breast cancer.


The assessment of sexual function in cancer patients.

The sexual function of cancer patients may be compromised by their disease or treatment. This is infrequently assessed as an outcome variable and methodological differences between reported studies make comparison difficult. Where sexual function is being assessed as one dimension of a more comprehensive assessment of quality of life, a single item concerned with frequency of intercourse or satisfaction may be sufficient, but many studies require more detailed information. Methods developed for clinical assessment of sexual dysfunction are generally too long and detailed for this purpose. The best developed scales for cancer patients are embedded in lengthy and expensive questionnaires. A pool of items can be identified from which a scale could be derived to assess the relevant aspects of sexual experience. The development of an appropriate and psychometrically sound scale is now required to encourage greater consideration of the impact of disease and treatment on cancer patients' sexual function.


Immunostaining of cathepsin D in breast cancer: quantification by computerised image analysis and correlation with cytosolic assay.

Cathepsin-D (cath-D) was quantified in 34 breast cancer specimens by immunohistochemical staining of frozen sections with a computer image analysis and the results were compared with the corresponding cytosolic assay. Cath-D concentrations varied from 0 to 420 arbitrary units (AU). Tumour cells were more intensely stained than peritumoral tissue with the D7E3 mouse monoclonal antibody than with rabbit polyclonal antibodies. There was a good correlation (r = 0.80) between cath-D values obtained either by immunohistochemistry with D7E3 antibody or by cytosolic immunoenzymatic assay. However, with a cut-off of 50 AU, 3 out of 25 patients had higher immunohistochemical values and 2 had higher cytosolic values. Therefore, quantification of cath-D concentration in tissue section by immunostaining and a computerised image analyser, which is the only technique available for small tumours, should provide similar prognostic information to that obtained by assaying cath-D in the cytosol.


Neuron-specific enolase as a prognostic factor in metastatic malignant melanoma.

Serum neuron-specific enolase (NSE) was measured in 63 patients with metastatic malignant melanoma. 20 patients (32%) had elevated serum NSE (> 10 micrograms/l) before the start of treatment. Another 13 patients (21%) developed pathological NSE values during the course of the disease. In many patients, elevated NSE was related to a large tumour burden, and a gradual rise in serum NSE indicated disease progression. Patients with elevated pretreatment NSE had a median survival time of 3 months compared with 12 months for those with normal pretreatment NSE values. NSE thus proved to be a useful prognostic factor in metastatic malignant melanoma.


Prognostic significance of pretreatment serum levels of squamous cell carcinoma antigen and CA 125 in cervical carcinoma.

Serum levels of squamous cell carcinoma antigen SCC, carcinoembryonic antigen CA 125, and tissue polypeptide antigen were determined in 142 patients with primary cervical carcinoma, 60 patients with precancerous lesions and in 129 healthy women. With regard to elevated tumour marker levels, specificity ranged from 94.6% to 97.7%. Sensitivity was highest (44.4%) for SCC. A stage relation was found for all tumour markers except for carcinoembryonic antigen. In stage Ib, SCC levels increased according to tumour volume. SCC, CA 125 or both markers were elevated in 7 of 8 patients with pelvic lymph node metastases compared with only 17 of 58 patients with negative nodes (P = 0.005). In a multivariate analysis, pretreatment serum levels of SCC and CA 125 were found to be significantly related to patient survival, in addition to stage. In cervical SCC, the risk of a fatal outcome increased 16 times with SCC levels > or = 4.5 ng/ml, compared with SCC levels < or = 1.3 ng/ml. We conclude that pretreatment serum levels of SCC may be of value as an adjunct to clinical staging. In addition, serum determinations of SCC and CA 125 seem to be useful in predicting the risk of pelvic lymph node metastases and as prognostic risk factors for disease outcome.


Care and costs for advanced cervical cancer.

The types, amounts and costs of hospital and home care in patients who died from cervical cancer are investigated, using both national data sources and hospital files. Our goal has been assessment of the savings on treatment and care of advanced cervical cancer resulting from cervical cancer screening. Hospital costs account for 70% of the total cost per patient of Dfl 29,200. The amount of hospital care decreases significantly with increasing age. The average number of days of hospitalisation per patient with advanced disease decreases from 62 days below age 50 to less than 10 days at age 70 and older. In-hospital medical procedures, home care and nursing home care account for 24, 22 and 8% of the costs, respectively. Mass screening programmes for cervical cancer will result in a reduction in both advanced disease and mortality. The potential savings compensate approximately 10% of the costs of screening.


Recent changes in the surgical management of T1/2 breast cancer in England.

Following the results of a study undertaken in 1985, a second survey was undertaken to examine whether there had been any changes in England in the surgical management of patients with a T1/2/NOMO breast cancer. The major findings were that: (i) there was a significant increase in the number of surgeons who would undertake breast conservation surgery; (ii) there was a significant increase in the number of surgeons who would discuss breast reconstruction where mastectomy was the preferred form of treatment; (iii) that significantly more surgeons would offer the patient a choice of surgery when there was more than one surgical option; and (iv) that significantly more surgeons had access to a breast specialist nurse and/or a cancer counsellor. These changes are consistent with the recommendations of the 1986 King's Fund Consensus' Conference for breast cancer treatment.


The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients.

The influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA) given intramuscularly on the peripheral aromatisation of androstenedione into oestrone was investigated in postmenopausal women with breast cancer and compared with the suppression of plasma oestradiol (E2). 7 patients were investigated before and during treatment on day 7, i.e. midway between two weekly injections. After an intravenous injection of [3H] androstenedione and [14C] oestrone, urine was collected for 96 h and the isotope ratio determined in the urinary oestrogen metabolites after isolation with high performance liquid chromatography. At 250 mg, 4OHA inhibited aromatisation to [mean (S.D.)] 15.2 (5)% of baseline (P < 0.002). There was significantly greater inhibition to 8.1 (2.7)% at 4OHA 500 mg (P < 0.01). Plasma E2 was reduced to 41.2 (14.1)% of baseline at 4OHA 250 mg with a further reduction to 32.7 (19.8)% at 500 mg (P < 0.05). These results confirm the dose-response relation previously established with plasma oestrogen measurements alone.


Thyroid function 10-18 years after mantle field irradiation for Hodgkin's disease.

Thyroid function was measured in 81 patients who had been curatively irradiated on a mantle field for Hodgkin's disease 10-18 years ago. 47 patients (58%) had elevated levels of thyroid stimulating hormone, indicating hypofunction of the thyroid gland, compared with 4.6% of controls (hospital visitors) matched for age and sex. The mean free thyroxine index (FTI) was significantly lower in patients than in controls, but all FTI values were still normal. Age at the time of irradiation, sex, time since irradiation and administration of chemotherapy were not significant factors in the development of thyroid dysfunction. A life-long awareness of the possibility of insidiously developing myxedema in these patients is strongly advocated.


Phase II study of interferon alfa-2a and dacarbazine in advanced melanoma. Biological Response Modifiers in Melanoma (BREMIM) Italian Cooperative Group.

In phase II, the tolerance and activity of dacarbazine and recombinant interferon alfa-2a (rIFN) was studied in 79 patients with metastatic melanoma. The regimen was well tolerated. Response rate was 25%, with 8% having a complete response. Response duration and survival after a follow-up of 39 months are reviewed. The mean durations of complete and partial responses are 13.7 months (range 1 to 31+) and 10 months (2 to 36+), respectively. Median time to progression is 3 months; median survival is 9 months. At present, 11% of treated patients are alive, thus addition of rIFN to dacarbazine may prolong response duration.


Additional ecological evidence: lipids and breast cancer mortality among women aged 55 and over in China.

That dietary fat increases breast cancer risk has been strongly supported by international data collected among developed countries during the past few decades. Population aggregates with elevated lipid intake have tended to report elevated breast cancer incidence and mortality. This study is an ecological analysis of the association of various indicators of lipid intake with breast cancer mortality in 65 county-wide population aggregates in the People's Republic of China. Although the result is consistent with a positive association between lipid intake and breast cancer risk, the observed association is weaker than the association previously observed. This finding provides only modest support for the possibility of a diet-breast cancer link.


Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T cells and decrease of "naive" (CD4-CD45R) T lymphocytes.

Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or "memory" T cells recovered completely, while the CD4-45R or "naive" T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells ("activated" T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. We propose that the recovery of the CD4 cells is limited to the CD4-w29 ("memory") population because of thymic dysfunction in older humans. The impact of the observed immune modulation on the low susceptibility for infections after local irradiation, and on putative antitumour immune responses is discussed.


Evidence for individual differences in the radiosensitivity of human skin.

Previously published clinical data have been re-analysed to investigate individual differences in the radiosensitivity of human skin. In the clinical studies, acute and late skin reactions were recorded for 254 breast cancer patients receiving radiotherapy to the internal mammary nodes following simple or modified radical mastectomy. Each patient was treated bilaterally with different fractionation schedules to the right and left fields. Patients were assigned prospectively to 10 different treatment groups of 11-35 patients each, with all patients in a group receiving the same pair of fractionation schedules to the right and left fields. In the present study, correlations between the skin reactions in the two treatment fields per patient were investigated. For each of three different endpoints--peak reflectance measure of erythema, peak acute skin reaction score, and a ranking measure of the progression rate of telangiectasia--significant correlations were found between the levels of skin injury to the right and left treatment fields of the patients in most treatment groups. Although there were correlations between the absorbed doses in the right and left fields, statistical analyses indicated that dose effects were not sufficient to explain fully the patient-to-patient differences in skin response. Thus, these data provide evidence for the existence of individual differences in the radiation response of human skin, both for early and late effects. Whether these differences are dominated by heterogeneity in intrinsic cell radiosensitivity or by other factors has yet to be determined. However, there was no clear evidence of a correlation between the acute and late endpoints, suggesting that the individual differences in radiosensitivity are not dominated by a common genetic component expressed equally in all cells.


A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy.

High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.


Elevation of ADP-ribosylation as an indicator of mononuclear leucocyte responsiveness in breast cancer patients treated with tamoxifen.

82 women who had had surgery for removal of breast cancer were randomised during the primary care period before initiation of any chemotherapy or radiotherapy into two groups: no drug treatment (n = 40) and 20 mg tamoxifen per day for 2 years (n = 42). Mononuclear leucocyte (MNL) fractions from blood samples were collected during the first 368 days of the study and ADP-ribosylation was quantified. Tamoxifen treatment resulted in a dose-duration increase in ADP-ribosylation. This was true even after adjustment for covariates such as age, smoking habits, oestrogen use, menstruation and tumour size. These data suggest that part of the antitumour effects of tamoxifen treatment in vivo relates to an enhanced immune cell responsiveness, as indicated by the increased MNL ADP-ribosylation.


Fotemustine plus dacarbazine for malignant melanoma.

119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1 and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine 100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4 weeks. 12 complete responses (11.6%) and 16 partial responses were observed in 103 evaluable patients (response rate 27.2%). The median duration of response was 21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral sites and 37.5% in non-visceral sites. The toxicity was mainly haematological: grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate was lower than that in 63 patients previously reported. The present series had a higher median age (54 vs. 40 years) without any differences in other population variables. However, activity on CNS metastases and on non-visceral sites was confirmed. Haematological toxicity was about 50% lower than that with fotemustine alone. Hence, this is an active outpatient regimen for metastatic melanoma, especially against cerebral and non-visceral metastases.


Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion.

Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A high performance liquid chromatography assay was used to measure melphalan concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01, Wilcoxon signed-ranks test), and not significantly different from levels in adjacent skin. In 2 cases there was significant regional toxicity in the treated limb, but this was not related to the levels of melphalan measured in the tissues of the limb. It is encouraging that the concentrations of melphalan which were achieved in large necrotic nodules by ILP were similar to those in well-perfused normal skin.


Fotemustine plus dacarbazine in advanced stage III malignant melanoma.

19 patients with advanced malignant melanoma were treated with fotemustine and dacarbazine. Data recorded and available for evaluation in all patients included clinical and histopathological parameters of the primary melanoma, blood chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial staging of the site of metastases and follow-up during treatment. Dosage was fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on days 1 and 8, repeated for a maximum of six courses. There were two complete and three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable disease. 6 (32%) patients had no response. Median length of complete and partial responses was 3.9 months, and that of stable disease 4.2 months. The main side-effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be new treatment in advanced melanoma.


Prognostic factors in patients with metastatic colorectal cancer receiving 5-fluorouracil and folinic acid.

We have reported that 5-fluorouracil (5-FU) and folinic acid increased response rate and survival in patients with metastatic colorectal cancer. Now we have analysed prognostic factors for response, toxicity, survival and time to progression. The variables used for survival and response were treatment centre, treatment, age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), site of disease, previous radiotherapy, site of primary, disease-free interval, initial alkaline phosphatase (AP), albumin (A), lactate dehydrogenase (LDH) and aspartate aminotransferase (SGOT). The significant independent variables for survival were PS of 2 or more, initial albumin and SGOT, and treatment received, in order of importance. The relative risk of death when patients received 5-FU/folinic acid was 60% of that of patients receiving 5-FU alone. The variables predictive of response were treatment and PS. The variables used for analysis of toxicity were age, treatment centre, treatment, sex, tumour response, PS, number of courses, SGOT, AP and albumin. Treatment was found to be predictive of toxicity. Thus, baseline albumin and SGOT, and 5-FU/folinic acid treatment are significant determinants of survival, 5-FU/folinic acid and PS of 2 or more are major determinants of response and no clinical parameter could be identified as a predictor of toxicity.


Phase II trial of 5-fluorouracil and recombinant interferon alfa-2B in metastatic colorectal carcinoma.

Between February 1990 and April 1991, 59 previously untreated patients with progressive and/or symptomatic metastatic colorectal carcinoma were enrolled in a phase II study of 5-fluorouracil (5-FU) and interferon alfa-2b (IFN-alpha). 5-FU 750 mg/m2/day was administered as continuous infusion for 5 days, then weekly in a dose of 750 mg/m2 as intravenous push injection starting on day 15. IFN-alpha 9 MU was given subcutaneously three times a week. Treatment was given for a maximum of 6 months. 55 patients are evaluable for response and 51 for toxicity. 17 patients (31%) achieved a partial remission, 15 (27%) had stable disease and 21 patients (38%) had progressive disease. Median duration of remission was 5 months and median survival for all patients 10 months. Toxicity was important with two treatment-related deaths and severe leukopenia, fever, diarrhoea and mucositis in about one third of the patients. In our opinion, this regimen is effective but rather toxic in metastatic colorectal carcinoma.


Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin in metastatic colorectal carcinoma.

148 patients with advanced untreated colorectal cancer were randomised to receive a weekly bolus of 5-fluorouracil (5-FU) 600 mg/m2 alone, with or without leucovorin (LV) 500 mg/m2. 5-FU plus LV produced a higher response rate than 5-FU alone: 23% (5 complete response, 11 partial response) vs. 8% (2 complete response, 4 partial response) (P = 0.03) out of 70 and 72 evaluable patients, respectively. Median survival was 11 months in both groups and median time to progression was not significantly different (P = 0.08). The combined regimen was more toxic than 5-FU alone, as evidenced by (a) a higher percentage of grade 3-4 diarrhoea, 19.5% vs. 8.5% (P = 0.045) and conjunctivitis, 26.5% vs. 5.6% (P = 0.0025); (b) the recording of one toxic death in the combined arm; and (c) the reduction of the median dose intensity of 5-FU actually delivered during the first 2 months of treatment. We conclude that 5-FU plus LV at a price of a higher toxicity is more active than 5-FU alone without improving survival and progression-free survival.


Phase II study of epirubicin sequential methotrexate and 5-fluorouracil for advanced colorectal cancer.

91 patients with measurable metastatic colorectal carcinoma entered a phase II study. A three-drug schedule; epirubicin (20 mg/m2), sequential methotrexate (150 mg/m2), 5-fluorouracil (600 mg/m2) with 1-h interval (EMF) with folinic acid rescue was given weekly three times followed by 2-3 weeks rest. 85 patients were evaluable for response. 5 patients (6%) experienced a complete response (CR), 20 (23%) a partial response (PR), 31 (37%) had disease stabilisation (SD) and 29 (34%) progressive disease (PD). The median survival time was 13.7 months in all patients (n = 91) and 14.0 months in those evaluable for response (n = 85). In patients with CR, PR, SD and PD the median survival time was 46.7, 19.8, 14.7 and 8.7 months, respectively. The response rate was significantly (P < 0.05) higher in tumours originating from the colon (41%) than in those originating from the rectum (18%) and also significantly (P < 0.001) higher in non-symptomatic than in symptomatic patients, 40 vs. 4%, respectively. The treatment was fairly well tolerated as an outpatient regimen, the main dose-limiting side-effect being diarrhoea. Deaths for septic fever, which may be attributable to the treatment were encountered in 3 patients, all with progressive cancer. Further studies to disclose differences in response rate in subsets of patients are warranted.


Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.


Radiation therapy in clinical stage I and II Hodgkin's disease. The Princess Margaret Hospital Lymphoma Group.

A review of the Princess Margaret Hospital experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. The RFR for those treated with involved field RT was 58.4% at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and 65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In a highly selected group of patients with no adverse features, i.e. with stages IA-IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions--the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of treatment selection based upon clinicopathological prognostic factors and the use of extended field RT confers excellent results in the treatment of clinical stage I and II Hodgkin's disease.


Chemotherapy versus radiotherapy in early-stage Hodgkin's disease: evidence of a more difficult rescue for patients relapsed after chemotherapy.

Six cycles of mechloretamine, vincristine, procarbazine and prednisone (MOPP) chemotherapy were randomly compared with extended field radiotherapy (RT) in 89 adult patients with pathological stage I-II A Hodgkin's disease (HD). 45 patients received RT and 44 were treated with MOPP. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 in the MOPP group. 12 patients relapsed in both groups. 10 out of 44 patients treated with MOPP died of HD, compared with only 2 in the RT group. 3 more patients died in the MOPP group following the occurrence of second cancers. 11 out of the 12 (96%) patients relapsing after RT achieved a second CR, compared with 6 out of the 12 (50%) patients relapsing after MOPP. Analysis of the response rate with salvage treatment, shows that, of the 12 patients who relapsed after MOPP, the pattern of relapse might predict the likelihood of achieving a second CR, whereas in the RT group a second CR was achieved regardless of the characteristics of relapse. Survival probability for relapsing patients at 80 months calculated from relapse was 85% in the RT group and 15% in the MOPP group (P = 0.02). With a median follow-up of more than 8 years, the overall survival of patients was significantly better for RT compared with MOPP; 93 and 56%, respectively (P < 0.001). On the basis of these results we conclude that, to date, RT alone remains the treatment of choice for adult patients with early-stage HD with favourable prognostic factors.


A comparison of gallium-67 single photon emission computed tomography and computed tomography in mediastinal Hodgkin's disease.

The role of gallium-67 single photon emission computed tomography (Ga-67 SPECT) in the assessment of mediastinal Hodgkin's disease was evaluated prospectively. Ga-67 SPECT and computed tomography (CT) were compared and correlated with clinical findings at initial presentation in 30 patients, 6 weeks after treatment, and 6 months later in 20 of the 30 patients. At initial presentation, active disease was detected on both imaging modalities on all occasions. 6 weeks after treatment CT showed residual mediastinal abnormality in 7 patients, whereas Ga-67 SPECT showed abnormal mediastinal tracer uptake in 3 patients. 6 months later CT showed residual mediastinal abnormality in 5 patients whereas all the Ga-67 SPECT studies were negative. Ga-67 SPECT imaging is a useful tool in assessing response to therapy in mediastinal Hodgkin's disease.


An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.


Surgical treatment of myeloma of bone.

33 patients treated operatively for plasma cell disease were analysed. There were 21 men and 12 women with an average age of 54 years. There was an undefined bone tumour in 23 cases, and a pathologic fracture in 10 cases. In only 6 cases was the diagnosis known before the operation. The primary tumour localisations were: vertebral column in 13, pelvis in 7, femur in 6, humerus in 2, rib in 1, tibia in 1, fibula in 1, scapula in 1 and olecranon in 1 case. 16 diagnostic biopsies were taken. Vertebral tumours were mainly evacuated or decompressed, combined with a stabilising procedure in 8 cases. A total of six endoprostheses, five to the femur and one to the humerus were performed. Two primarily wide resections, to the fibula and to the scapula were done. There were no locally recurring tumours during a mean follow-up time of 4 years and 2 months, and we conclude that operative and oncologic treatment is successful in providing the patient with a stable, pain-free locomotive system.


Screening for psychiatric disorders in a lymphoma out-patient population.

The Hospital Anxiety and Depression Scale (HADS), a four-point, 14-item self-assessment questionnaire, was tested as a screening method for psychiatric disorders in a sample of 117 Hodgkin's lymphoma and non-Hodgkin lymphoma consecutive out-patients. A receiver operating characteristic (ROC) analysis was performed, giving the relationship between the true positive rate (sensitivity) and the false positive rate (1--specificity). This makes it possible to choose an optimal cut-off score that takes into account the costs and benefits of treatment of psychiatric disorders (mainly adjustment, depressive and anxiety disorders) in a lymphoma out-patient population. A cut-off point of 10 gave 84% sensitivity and 66% specificity. HADS appears in this study to be a well accepted, simple, sensitive and specific tool.


High-dose and low-dose combined oral contraceptives: protection against epithelial ovarian cancer and the length of the protective effect. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relations between use of high-dose and low-dose combined oral contraceptives and epithelial ovarian cancer were compared in an international hospital-based case-control study. 393 cases from seven countries were compared with 2561 matched controls. The odds ratio (OR) was somewhat lower for women who used high-dose oestrogen oral contraceptives (OR = 0.68) than for women who used low-dose preparations (OR = 0.81) although the difference could have occurred by chance. After controlling for time since last use, risk was slightly lower for long-term users of high-dose preparations than for long-term users of low-dose pills. Both high-dose and low-dose oral contraceptives protect against ovarian cancer, but the degree of protection may be slightly weaker for the newer, low-dose products.


Doxorubicin weekly low dose administration: in vitro cytotoxicity generated by the typical pharmacokinetic profile.

The cytotoxic effects of prolonged exposure to low concentrations of doxorubicin or a doxorubicin bolus were examined in vitro on four human breast cancer cell lines to simulate the plasma concentration profile of weekly low-dose (WLD) doxorubicin in breast cancer patients. Cells were exposed to doxorubicin for various prolonged times (24, 72, 120 and 192 h) and with different drug concentrations (5, 10, 20, 50 and 80 nmol/l). In a series of parallel experiments, cell lines were placed in contact with the drug for short periods (1 h) before prolonged exposure to doxorubicin; the concentrations of these pulses were 150, 250 and 350 nmol/l. A constant decrease in tritiated thymidine incorporation was noted as a function of the drug concentration and the duration of the cell contact with the drug. Interestingly the lowest concentrations (5-10 nmol/l) produced marked cytotoxic effects. For equivalent concentration x time values, experiments including doxorubicin pulses resulted in greater cytotoxicity than continuous exposure alone, in a dose-related manner. This finding was related to differences in intracellular doxorubicin concentrations. Results suggest that the rather empirically designed WLD doxorubicin schedule can generate greater cytotoxic effects than continuous doxorubicin administration alone.


Synergistic antiproliferative activity of tamoxifen and cisplatin on primary ovarian tumours.

We looked for the presence of the so-called type II oestrogen binding sites (EBS), in four oestrogen (ER) and progesterone (PR) receptor negative primary ovarian tumours. Moreover, the colony-forming assay was used to evaluate the response of ovarian cancer cells from these primary tumours to tamoxifen and cisplatin used alone or in combination. All tumours contained type II EBS, and tamoxifen was able to compete for [3H] oestradiol binding to these sites. Cisplatin and tamoxifen exhibited a dose-dependent inhibition of colony formation in a range of concentrations between 10 and 1000 micrograms/l and 37 and 3710 micrograms/l, respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity, with a potentiation up to and beyond 50-fold. Our results show that in ovarian cancer tamoxifen interacts with type II EBS with an affinity consistent with the concentration effective both in inhibition of colony formation and in synergising cisplatin activity. Based on the experiments performed the action of tamoxifen on cell growth is independent of ER expression, and could be mediated by type II EBS. The possibility that the association of tamoxifen and cisplatin may result in an improved clinical response in ovarian cancer should be investigated.


Growth stimulation of a human colorectal carcinoma cell line by interleukin-1 and -6 and antagonistic effects of transforming growth factor beta 1.

We analysed the effect of interleukin-1 (IL-1), IL-6 and transforming growth factor beta 1 (TGF beta 1) on the growth of a panel of eight colorectal carcinoma cell lines. IL-1 stimulated growth of two lines (LS411N and LS1034) up to 20-fold and IL-6 enhanced proliferation of LS1034 more than 5-fold. Both cytokines also augmented colony-formation of LS1034 in methylcellulose. Under both growth conditions IL-1 was the most potent stimulator. However, the addition of IL-6 to IL-1 synergistically enhanced proliferation of LS1034 in monolayer culture and additively augmented the number of colonies formed in methylcellulose. Furthermore, TGF beta 1 strongly reduced the growth rate of LS1034. Low amounts of TGF beta 1 markedly inhibited the response of LS1034 to IL-1 and totally abrogated proliferation induced by IL-6. We conclude that different cytokines can provide distinct signals for the regulation of growth of colorectal carcinoma cells.


Tumour-infiltrating lymphocytes in cervical carcinoma.

Tumour-infiltrating lymphocytes from cervical carcinomas were cultivated in the presence of interleukin-2. The majority of bulk cultures were cytotoxic against K562, Mel 1 and Caski cells. CD8+ cells were the predominant subset in over 50% of cultures, with varying numbers of CD56+ and CD25+ cells. T cell clones were established from six tumour-infiltrating lymphocyte cultures and the majority exhibited non-MHC-restricted cytotoxicity. However, in one case cytotoxicity of several derived clones was limited to the autologous tumour and in another, to the autologous tumour and Caski cells. This study indicates that tumour-infiltrating lymphocytes can be amplified and cloned from cervical carcinoma biopsies in the presence of rIL2. Although the predominant cytolytic function is non-MHC-restricted, low autotumour cytotoxicity can be demonstrated at the clonal level. The nature of the antigen(s) recognised by T cells on autologous cervical carcinoma cells in unknown; the candidacy of human papillomavirus-related products requires investigation.


The management of Hodgkin's disease in relapse after primary radiation therapy.

Approximately 20-25% of patients with stage I-II Hodgkin's disease treated initially with irradiation alone will experience a relapse of disease. Restaging at the time of relapse provides a useful prognostic indicator and may help in the selection of salvage therapy. Systemic treatment is indicated in nearly all patients. In the Stanford experience, 109 patients who relapsed were treated with MOPP (or MOPP-like chemotherapy) with or without local irradiation. The actuarial 10-year survival and freedom from second relapse were both 57%. Important prognostic factors included 'relapse stage' (IA vs. II-IIIA vs. I-IIIB or IV) and type of salvage therapy (combined modality vs. chemotherapy alone). Important issues in management of these patients include the selection of chemotherapy agents, whether to incorporate localised irradiation, and the use of even more aggressive salvage treatment programs, such as autologous bone marrow transplantation, in selected patients with a very poor prognosis.


The South Australian Cancer Registry: a means of assessing cancer incidence, mortality and case survival.

In 1977, a Cancer Control and Surveillance Unit was established by the South Australian government. The infrastructure of the Unit was the State's Cancer Registry which was established simultaneously. By 1990, approximately 70,000 invasive cancer cases had been notified to the Registry for a population which had increased from 1,287,550 in 1977 to 1,400,000. In 1990, 2940 cancers were notified in males and 2640 in females. The leading sites in males were the prostate, lung, colon and melanoma of the skin, while in females they were the breast, colon, melanoma of the skin and lung. An increase in age-standardised incidence rates for all cancer sites combined has been documented for the 1977-1990 period. The magnitude of the increase was 7% in males and 12% in females. Meanwhile, there were 1544 male cancer deaths and 1203 female cancer deaths in 1990. Amongst males, age-standardised mortality rates tended to decline in the 1980's, due largely to a reducing age-standardised incidence of lung cancer. By comparison, an increased lung cancer incidence in females contributed to an overall increase of 6% in the age-standardised mortality rate for cancers of all sites combined in this sex during the life of the Registry. During the period 1977-1990 there was a 55% increase in the number of new invasive cancers in males and females combined. Most of this increase can be attributed to the ageing of the South Australian population and to a much lesser degree to population growth. During the same period there was a concomitant increase in 43% in the number of deaths where the underlying cause of death was cancer. Case survival rates are found to be very similar in South Australia to those reported for the United States, with about 51% of cases surviving their cancers 5 years after diagnosis. 5-year survival rates for the diagnostic period, 1983-1990, were generally better than for 1977-1982. The evidence for improved survival was strongest for cancers of the oesophagus, colon, cervix, prostate and testes, and for low-grade and medium-grade lymphomas and chronic myeloid leukaemias. When case survival rates were calculated for childhood tumours, significant improvements were found for acute lymphatic leukaemias and non-Hodgkin lymphomas for the diagnostic period, 1983-1990, when compared with 1977-1982.


[Incidence and surgical treatment of extrahepatic abdominal hydatidosis].

From 1974 to May 1991, 417 patients with abdominal hydatid cyst disease were surgically treated. Twenty-eight patients had extrahepatic abdominal cyst disease (6.7%). Six patients had only extrahepatic disease where as 22 had associated hepatic and extrahepatic cysts. Most frequent sites were the peritoneum (52.7%), the spleen (22%) and pelvis (11%). Fourteen out of the 14 CT scans performed, detected the extrahepatic cysts. The preferred surgical technique was total closed cystectomy (in hepatic and extrahepatic cysts). Resection of the organ affected (8 splenectomies, 1 nephrectomy, 1 partial vertebral resection, 1 orchiectomy and 1 salpingo-oophorectomy) was also performed. There was no mortality and morbidity was 32.1%: 3 intraabdominal abscesses, 1 intraabdominal haemorrhage, 4 biliary fistulae and 1 partial necrosis of the large bowel. Only 3 patients (neither were treated with mebendazole) were reoperated on for recurrent peritoneal hydatic cyst.


[Inflammatory fibroid polyp of the ileum].

A new case of ileal inflammatory fibroid polyp (IFP) is reported. A 76 years old woman presented with abdominal pain due to intestinal obstruction; an ileo-ileal intussusception caused by an ulcerated submucosal polyp was found at laparotomy. The IFP usually appears as a solitary benign lesion, rarely located in the ileum. It is made up of fibrous tissue with a dense infiltrate composed predominantly of eosinophils.


[Ulcerative colitis and amyloidosis. Presentation of a case and review of the literature].

A case of ulcerative colitis associated with secondary amyloidosis in a 62-year-old man who died from septic shock and pneumonia complicating head injury is reported. Amyloid deposition was incidentally found at autopsy. Proteinuria and hepatomegaly discovered a few days before his death were the only signs of amyloidosis. The postmortem examination showed chronic ulcerative colitis (remitting form) with pseudo-polyps and amyloid deposition in the liver, spleen, pancreas, rectum, adrenals and kidneys. Although secondary amyloidosis complicating with Crohn's disease has been frequently reported, amyloidosis associated with ulcerative colitis has been exceptionally described and only 10 cases have been collected from the literature.


[Bone metaplasia in colorectal carcinoma].

We report two cases of osseous metaplasia in the polypoid areas of colorectal carcinomas. This is an extremely rare condition with no more than 30 cases published, that has to be recognized to avoid misinterpretations on biopsies or surgical specimens. The pathogenesis is unknown and it does not change the biological behaviour of these tumors.


[Acute viral hepatitis A and C: report of a case].

We present a case of acute hepatitis by simultaneous A and C virus infection. The coinfection was suspected due to the high levels of transaminases lasting more than 9 months after onset of the illness. During the early stages of the illness, the patient had IgM antibodies to hepatitis A virus. Serological tests for hepatitis B and C viruses, cytomegalovirus and Epstein-Bar virus were negative. Due to the persistently high transaminase levels, we repeated the serology, detecting positive results for hepatitis C antibody, while hepatitis B serology remained negative as well that for all other virus tested. With these findings, we believe that a patient with hepatitis A of long duration, requires additional serological examinations to determine the possibility of coinfection by another virus.


[Dubin-Johnson syndrome. Presentation of 3 cases. Review of the national literature].

Three patients, two male and one female, 42, 64 and 20 years old respectively, with a Dubin-Johnson syndrome are reported. Both men referred jaundice since several years and in the woman's case, the onset of the illness took place during the last term of her second pregnancy. In two patients, liver aspect and it's biopsy were diagnostic. In the other, who was hospitalized because of a myocardial infarction, a hepatic gammagraphy with Tc 99 HIDA was made. No case was associated with biliary lithiasis and only one patient had other members in his family with the illness.


[Digestive hemorrhage caused by gastric varices: usefulness of the techniques of endoscopic sclerosis].

Upper gastrointestinal hemorrhage secondary to gastric varices still has a high death rate. Fourteen patients were admitted to our unit with bleeding gastric varices from November 1989 to August 1991. Endoscopic injection sclerotherapy obtained control of the bleeding in 92.3%; however, recurrences occurred in 33% of these cases in the first 24-48 hours, with a death rate of 50% during the second stage of the upper gastrointestinal hemorrhage. Total mortality rate was 21.4%. Of the fourteen patients, nine exhibited junctional varices, while five hand fundic varices. In ten of the fourteen patients, gastric varices developed during esophageal sclerotherapy. While hospitalized, it was observed that patients with gastric varices in the fundus had more recurrences and mortality, than those located next to the cardio-esophageal junction. Sclerosis of the varices only obtained temporary control of the bleeding with greater frequency of recurrences and mortality.


[Gastric emptying of solids, acid secretion and tobacco in duodenal ulcer].

We study in a group of patients with endoscopically diagnosed duodenal ulcer (19; 17 males) and controls (11; 7 males) the gastric emptying of solids through scintigraphy and gastric acid secretion by standard tests. In the same way we investigated prospectively some clinical data, specially smoking habits. As a whole, patients with duodenal ulcer showed an emptying of solids slightly faster than controls (T 1/2-minutes-: 85.4 +/- 28.6 in patients with duodenal ulcer versus 116.9 +/- 46.5 in controls, p less than 0.03). However, most of our patients (15 of 19 or 79%) were found to have a normal emptying rate. No correlation was found between secretory outputs and gastric emptying. Smokers with duodenal ulcer had a faster emptying that non-smokers with duodenal ulcer (T 1/2 74.8 +/- 30.05 vs. 99.91 +/- 19.86; p = 0.05).


[Intestinal inflammatory disease in the province of Soria. Retrospective clinical and epidemiologic study from 1981 to 1990].

The inflammatory bowel disease cases in Soria have been reviewed from 1981 to 1990. Thirty-two cases of ulcerative colitis (UC) and thirteen cases of Crohn's disease (CD) have been found. The mean incidence was 3.2/100.000 inhabitants/year in UC and 1.3/100.000/inhabitants/year in CD. The prevalence was 32 and 13/100.000 inhabitants respectively. We have found a progressive increase in incidence in both UC and CD during the period analyzed. Epidemiologic data (considering the majority come from rural areas), clinical course, endoscopic and radiologic findings, are similar to the results published in the literature. We have found a minor percentage that other authors in extraintestinal signs, complications and need of surgical intervention.


[Trophic activity of neurotensin in massive intestinal resection].

Regulatory peptides are among the main factors affecting the proliferative adaptive process of the small bowel; its mechanisms of action remains unknown. An 80% small bowel resection was done in Wistar rats (250-300 g) randomly assigned to two groups: control and neurotensin (300 mu/kg). Jejunal and ileal samples were taken on day 14 post-resection and histomorphometric (villous length) and proliferative (DNA content) measures were obtained. Results show an increase in villous length in the neurotensin group but no changes in DNA content were observed. We conclude that neurotensin increases intestinal mucosal growth after massive intestinal resection in the rat.


[Prevalence of hepatitis B markers in non-hospital health personnel].

Through a hepatitis B prophylaxis campaign, vaccination and serological study was offered to 316 nonhospital health personnel of the Health Area of Gandia (Valencia). 117 people volunteered (37%); among them, nurses showed the highest participation (45.8%) in comparison with doctors, nursing auxiliaries and non-technical personnel (p less than 0.05). In 22 cases a positive marker could be proved; therefore, total prevalence (18.8%) was significantly higher than that of the control group, which was 6.8% (p less than 0.01). This prevalence is compared with other groups of hospital and nonhospital personnel, and the convenience of new studies and the recommendation of active prophylaxis for this subset of health workers are discussed.


[Clinical and histochemical findings in spinal muscular atrophy].

The childhood form of the spinal muscular atrophy (SMA) is classically subdivided into three groups on the basis of a combination of age of onset, milestones of development and age of survival: acute Werdning-Hoffmann (type I), intermediate Werdnig-Hoffmann (type II) and Kugelberg-Welander disease (type III). Now we examined 7 cases of type I and 9 cases of type II on clinical and histochemical ground. Of the total of 16 cases, 5 cases had a family history of the disease. (1) In type I, three were males and 4 females. The onset was within 30 days and the disease was manifest before or at delivery in 3 cases. The progression was so severe. All cases were dead by 10 months. They showed generalized hypotonia, abnormal respiration and could not sit without support. In type II, five were males and 4 females. The onset of the disease was between the age of 3 and 15 months. The progression was slow. All patients couldn't walk by themselves at all but 7 of them had abilities to sit without support. Clinically it was easy to classify type I from type II. (2) The most characteristic histochemical findings of both types were group atrophy, fiber hypertrophy, fiber type predominance and fibrosis. Though there was a slight difference between two types in histological pattern, the basis was so similar. There is controversy about the proper classification of recessive childhood SMA. Now it is suggested that the majority of both acute and chronic cases are allelic, similar to the patterns of Duchenne and Becker forms of muscular dystrophy.


[Cool storage of fetal rat brain for neural transplantation].

The availability, storage and transportation of donor tissue are major practical problems associated with the potential use of grafted neural cell replacements in neurodegenerative diseases. The capacity to collect and maintain viable fetal neural tissue would facilitate possible clinical applications, and provide opportunities to study various neural diseases. In the present study, we examined the effect of cool storage on the survivability of intraventricular rat fetal ventral mesencephalic grafts (gestational days 15). In all experiments, fetal ventral mesencephalons were dissected out under a dissecting microscope in calcium-free magnesium-free buffer (CMF: 0.15 M NaCl, 0.008 M Na2HPO4, 0.0027 M KCl, 0.0015 M KHPO4, 0.026 M NaHCO3, with 0.1% glucose, 100 micrograms/ml streptomycin, 2.5 micrograms/ml fungizone). Fetal mesencephalic tissue was grafted into the lateral ventricle following pregraft refrigeration in calcium-free magnesium-free buffer at 4 degrees C. Fetal mesencephalic tissue was hibernated for 5, 12, 16, 20, 24, 28, 32 hours (group A, B, C, D, E, F and G, respectively). As a control group, fetal mesencephalic tissue was grafted into the lateral ventricle immediately after dissection. Grafted fetal mesencephalic tissue which had been hibernated for 16 hours or less survived well. There were no significant decreases in the size of grafts among group A, B, C and the control group. In group A, B, C and the control group, clusters of TH-positive neurons and dense networks of neuritic profiles within the grafts provided a morphological appearance reminiscent of the dendritic bundles that characterize the zone reticulate of the substantia nigra in situ.(ABSTRACT TRUNCATED AT 250 WORDS)


[Seizure susceptibility in aged rats--pentylenetetrazol-induced seizures and amygdaloid kindling seizures].

Seizure susceptibility in male aged rats (21-25 mo. age) was investigated by pentylenetetrazol (PTZ)-induced seizures and amygdaloid kindling seizures. Male adult rats (3-4 mo. of age) were used as the control group. During 60 min. after the administration of PTZ (70 mg/kg, s.c.), the aged rats had a higher incidence and a significantly longer duration of generalized convulsion than the control group. On the other hand, the kindling rate of the aged rats was significantly slower than that of the control. The aged rats remained longer at stage 1-2 indicative of partial seizures. However, the aged rats skipped stage 3 on their way to stage 4-5 (generalized seizures), and showed a more violent stage 5 seizure than the control group. They had a longer duration of afterdischarges (AD) through the kindling process with a significantly faster propagation of AD to the contralateral amygdala as compared with the control group. The present study suggests that aged rats are prone to convulsion, while they have a difficulty in acquisition of epileptogenesis.


[Significance of the factors in wound healing for the origin of chronic subdural hematoma--fibronectin and its related substances].

The role of substances for wound healing in chronic subdural hematoma was investigated. Fibronectin, blood coagulation factor XIII (F X III), alpha 2 -plasmin inhibitor (alpha 2-PI) and alpha 2-PI plasmin complex (PIC) in hematoma fluid were measured, sixty cases of hematoma fluid (15 cases were bilateral chronic subdural hematomas) were used for analysis. The levels of fibronectin in hematoma fluid ranged widely from 40 to 1068 micrograms/ml. The levels of F XIII (except 1 case) in the hematoma fluid were less than 70% (normal plasma level 72-144%). And also the levels of alpha 2-PI in the hematoma fluid were lower than that in normal blood plasma (85-115%). Fibrin, fibronectin, alpha 2-PI and collagen crosslinks to these proteins by the catalytic action of the activated F XIII. These substrate proteins (except fibronectin) and F XIII were extremely low levels for wound healing. Histological analysis of the membrane with dura mater obtained from 13 patients was performed by Abidin-Biotin peroxidase Complex Method. Fibronectin was identified in outer membrane especially in sinusoidal layer. In normal wound healing, fibronectin appears early with the invading fibroblast and disappeares within 5 weeks from injury. But in chronic subdural hematoma it was not disappeares in 8 weeks after the head injury. The fact indicates the neomembrane of the chronic subdural hematoma is not in healing stage. This condition in chronic subdural hematoma is unfavorable for wound healing. Thus, author suspected that in early phase of wound healing after the head injury fibronectin and its related substances may play a role in the formation of chronic subdural hematoma.


[An autopsy case of neuronal type Charcot-Marie-Tooth disease (HMSN type II) with nerve deafness and psychiatric symptoms].

The clinical and pathological findings of a 41-year-old male patient with atypical Charcot-Marie-Tooth disease were reported. There were 3 cases of subarachnoid haemorrhage, 2 nerve deafness and 2 hereditary motor and sensory neuropathy (HMSN) in his family. He had suffered from progressive nerve deafness since 5 years old and gait disturbance since 37 years old. He had been admitted to the psychiatric hospital 3 times because of hallucinatory-delusional state and behavior abnormalities. Neurological examinations at 39 years old revealed that he had mental deterioration (IQ 66), nerve deafness, diffuse muscle atrophy, most marked distally, sensory disturbance, areflexia, positive Romberg's sign, orthostatic hypotension, dysphagia and slurred speech. MCV of median nerve was 27.8 m/sec, and SCV was not evoked. EEG revealed nonspecific dysfunction of the brain. He died of ileus-like condition at 41 years old. General autopsy showed haemorrhagic infarction of the jejunum and ileum due to compression of the superior mesenteric artery and vein by an adhesion band of connective tissue formed after previous appendectomy. Neuropathological examinations revealed axonal degeneration and loss of myelinated fibers with schwannosis of anterior and posterior spinal nerve roots as well as peripheral nerves. The posterior roots were more severely affected than the anterior ones. Ganglion cells of the posterior root ganglia showed remarkable degeneration and loss. There was severe degeneration of the posterior columns, especially in the gracilis, of the spinal cord. Nerve cells in the anterior horns and Clarke's columns also displayed conspicuous atrophy or central chromatolysis followed by gliosis. There was slight degeneration of the posterior spinocerebellar tracts.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diffuse reduced uptake in 99m-Tc-HM-PAO SPECT and high level of neuron-specific enolase in cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease].

We report an autopsy-diagnosed case of Creutzfeldt-Jacob disease (CJD) showing diffuse reduced uptake in SPECT and a high level of neuron-specific enolase (NSE) in the cerebrospinal fluid (CSF). A 75-year-old woman with a 3-month history of progressive gait ataxia and dementia was examined. Four months after onset of the disease, she developed an akinetic mutism with normal CT and MRI. She was admitted for further examination, and electroencephalography showed periodic synchronous discharges. NSE in the CSF showed a high level at 90.6 ng/ml, and SPECT showed diffuse reduced uptake in the supratentorial region, with relatively spared uptake in the cerebellum. She died 13 months after onset of the disease, and the autopsy diagnosis was CJD. SPECT data and the level of NSE in CSF seem to be useful for clinical diagnosis and pathogenetic analysis in the early stage of CJD.


Inhaled beclomethasone decreases serum osteocalcin in postmenopausal asthmatic women.

There are very few data as yet to quantify the effect of inhaled corticosteroids on bone metabolism, although the use of these drugs as a first-line treatment in bronchial asthma has widened. We determined the effect of three dose levels (200, 1000, 2000 micrograms/day, three weeks each) of inhaled beclomethasone on specific characteristics of bone metabolism in nine postmenopausal women with new asthma without any previous corticosteroid therapy. Significant decrease was noted in the mean serum morning osteocalcin concentration between the baseline and after nine weeks of beclomethasone (from 4.4 to 3.1 micrograms/l, p = 0.005). Significant increase in serum total and ionised calcium was found, although the parameters measuring bone resorption itself did not change. The results show that especially high-dose inhaled beclomethasone decreases serum osteocalcin in post-menopausal asthmatic women. Further studies are needed to assess the effects of inhaled beclomethasone, both on the ability of the osteoblasts to form bone matrix and on the density of bone during a longer treatment period on inhaled corticosteroids.


Standardization of tibial fractures in the rat.

The influence of the fracture level on the biomechanical properties of healing rat tibial fractures has not been investigated so far, despite the widespread use of rats in fracture healing studies. Fractures were produced in four different zones in the right rat tibia and immobilized with a K-wire. A fifth group of rats was not fractured. After 40 days of healing the fractures and the non-fractured bones were tested in three-point bending. A distinct correlation was found between fracture level and mechanical parameters: maximum load, maximum stiffness, and maximum stress decreased the more distal the fracture was located. In the non-fractured bones, maximum load and maximum stress were constant in all four zones tested, whereas energy absorption increased in the distal part of the tibia. No influence of the healing fracture was found on the contralateral, non-fractured tibia, compared with the animals left undisturbed, and the mechanical properties of the right and the left tibia were found to be symmetrical in terms of mean values. Four different methods of determining the area moment of inertia were investigated, and the simple method of approximating the cross section to an elliptical annulus was found to correlate well with the area moment of inertia, determined from computer tracings of bone slices prepared from the test specimens after the bending test. The computer tracings were corrected for the compression of the specimens caused by the mechanical test.


Age-dependent morphometric alterations in the distal femora of male and female rats.

Morphologic parameters, bone area, bone-to-bone + marrow ratio, periosteal-to-periosteal + endocortical surface ratio, mean trabecular thickness, and surface-to-volume ratio were studied in the epiphysis and metaphysis of the distal femora of male and female rats (Heiligenberg strain) between birth and the end of the lifespan. With increasing age, bone area, bone-to-bone + marrow ratio, and mean trabecular thickness increases, whereas periosteal-to-periosteal + endocortical surface ratio and surface-to-volume ratio decreases in both parts of bone during the first 150 days. Afterwards, periosteal-to-periosteal + endocortical surface ratio, mean trabecular thickness, and surface-to-volume ratio remain constant, whereas the bone area and the bone-to-bone + marrow ratio decrease. Modeling data were measured by use of the vital labeling technique with calcein. From the stained bone area, the bone formation, the bone resorption, and the periosteal mineral apposition rates have been calculated. The bone formation rate, about 13,000%/year in the metaphysis and 2,000%/year in the epiphysis, respectively, is greatest after birth and decreases continuously with increasing age to 3.5%/year for both bone regions. During the first 150 days the bone resorption rate is lower than the bone formation rate, leading to an increase in bone area, but afterwards it is higher so that the area decreases. Likewise the periosteal mineral apposition rate is greater in the metaphysis (24 microns/day at day 50) than in the epiphysis (14 microns/day at day 50), but after 700 days it is comparable for both bone regions (0.07 microns/day). The absolute values of body weight, femur length, and bone area of epiphysis and metaphysis are greater in male rats; only the mean trabecular thickness and the periosteal mineral apposition rate are comparable in both sexes. The relative values of bone-to-bone + marrow ratio, periosteal-to-periosteal + endocortical surface ratio, bone formation rate, and bone resorption rate are comparable for both sexes.


Lack of changes in histomorphometric, bone mass, and biochemical parameters in ovariohysterectomized dogs.

A predictable animal model with skeletal remodeling characteristics similar to those of humans is needed to facilitate the understanding of the mechanism of postmenopausal osteoporosis. We have utilized the ovariohysterectomized (Ovh) dog to examine cellular and biochemical responses to estrogen depletion and PTH stimulation. Histomorphometric measurements of bone biopsies taken prior to (first biopsy) and five months after the operation (second biopsy) showed no significant differences in static and dynamic parameters. Bone mineral density of the excised vertebrae displayed the same values between the two groups six months after surgery. Between the second biopsy and sacrifice, two infusion studies were performed. A two-hour infusion of EDTA followed by a two-hour recovery period elicited a rapid response in PTH production, highly correlated to the changes in ionized calcium, but no significant difference in response was observed between Sham and Ovh groups. A short-term (24-h) infusion of 1-34 hPTH increased circulating ionized calcium and 1,25-(OH)2-D levels to a similar extent in both groups. The levels of alkaline phosphatase were constant and both groups showed a small but nonsignificant increase in osteocalcin. The lack of sizable responses in histomorphometric, bone mass, and biochemical parameters may limit the utility of dogs for the study of cancellous bone loss in ovarian-dysfunction osteoporosis.


Dual-energy X-ray absorptiometry of lumbar vertebrae: relative contribution of body and posterior elements and accuracy in relation with neutron activation analysis.

The bone mineral content of 34 lumbar vertebrae obtained from ten cadavers (three men, seven women; age 61-88 years) was measured using a pulsed source dual-energy X-ray absorptiometry (DEXA) apparatus. Scanning was performed in the frontal projection and was repeated on the vertebral bodies obtained after removal of the posterior elements of the vertebrae. Subsequently a nondestructive neutron activation analysis (NAA) was performed. The mineral content of the vertebral bodies was found to represent (mean, SEM) 53.0% (1.9%) of the content of the whole vertebrae. The mineral content of the vertebral bodies assessed with NAA (BMC NAA) and with DEXA (BMC DEXA) showed a high correlation: BMC NAAA = (1.016 x BMC DEXA) + 0.990 r = 0.949 (p less than 0.001). We conclude that the mineral content of lumbar vertebral bodies can be accurately measured in vitro in a water environment by DEXA, and that the mean contribution of the posterior elements of the vertebra to the calcium hydroxyapatite content of whole vertebrae measured in the frontal projection is as high as 47.0%.


Inhibition of bone resorption by the bisphosphonate BM 21.0955 is not associated with an alteration of the renal handling of calcium in rats infused with parathyroid hormone-related protein.

Hypercalcaemia of malignancy is determined by an increase of bone resorption and/or renal tubular reabsorption of calcium (Ca). However, this latter component has been found to vary in certain patients during therapy with bone resorption inhibitors such as bisphosphonates. We investigated the possible effects of the highly potent bisphosphonate BM 21.0955 on the renal handling of Ca in thyroparathyroidectomized rats made hypercalcaemic by the stimulation of both bone resorption and renal tubular reabsorption of Ca induced by the chronic infusion of parathyroid hormone-related protein (PTHrP). Dose-dependent inhibition of bone resorption by BM 21.0955, as indicated by the decrease in fasting urinary Ca excretion from 64.0 +/- 7.3 to 6.7 +/- 3.1 nmol/ml GFR, was associated with a change in plasma Ca from 2.97 +/- 0.10 to 2.63 +/- 0.16 mmol/l. However, the relationship between urinary Ca excretion and plasma Ca was not altered, either at endogenous plasma Ca concentration or during the acute infusion of Ca. Similarly, an index of renal tubular reabsorption of Ca calculated from the slope of the linear portion of the relationship between urinary Ca and plasma Ca, which was increased by PTHrP administration, was not influenced by BM 21.0955 therapy (2.59 +/- 0.15 vs. 2.55 +/- 0.11 mmol/l GFR). These results indicate that BM 21.0955, which is one of the most potent bisphosphonates inhibiting bone resorption, did not affect the renal tubular reabsorption of Ca enhanced by PTHrP.


Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture.

The stability of trabecular bone depends not only on the amount of bone tissue, but also on the three-dimensional orientation and connectedness of trabeculae, which is summarized as trabecular microarchitecture. In previous studies we could demonstrate that in three-dimensional bone tissue the relation of trabecular plates to rods is reflected in the ratio of concave to convex surfaces of the bone pattern in two-dimensional bone sections. For the quantification of the connectedness of these bone patterns we developed a new histomorphometric parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that the connectedness of structures can be described by the relation of convex to concave surfaces. A lot of concave surfaces represent a well connected spongy lattice, whereas a lot of convex surfaces indicate a badly connected trabecular lattice in two-dimensional sections. By means of an automatic image analysis system we measure trabecular bone area (A1) and perimeter (P1). A second measurement of these two parameters (now A2 and P2) is done after a simulated dilatation of trabeculae on the screen. This dilatation results in a characteristic change of bone area and perimeter depending on the relation of convex to concave surfaces. TBPf is defined as a quotient of the difference of the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that there is not only age-related loss of bone volume, but also a decrease of trabecular connectedness. By means of TBPf we can demonstrate a significant difference in the age-related loss of trabecular connectivity between male and female individuals.


Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.


Development and evaluation of an index to predict early postmenopausal bone loss.

An index to predict individual postmenopausal bone loss is presented. The index is developed by means of data from a 10-year prospective Norwegian study in which bone mass of the distal forearm was measured annually in 73 women. All the women were 47 years old and premenopausal at inclusion. Independent risk factors for postmenopausal bone loss were identified by applying multivariate regression analysis on anthropometric, biochemical, nutritional, and life-style variables measured at menopause. The analysis identified low body weight, reduced renal phosphate reabsorption, and smoking as significant independent risk factors, and by means of these three factors a predictive index for postmenopausal bone loss was developed. This index was validated by using data from a 10-year longitudinal Dutch study, in which bone mass of the proximal radius was measured annually in 86 women, aged between 49 and 57 years and perimenopausal at inclusion. We defined women with the highest index score as "high-risk persons." According to this definition approximately 25% of the perimenopausal women were classified as high-risk persons, and the estimated sensitivity/specificity/positive predictive power were 36%, 89%, and 74%, respectively, when used to select women with a postmenopausal bone loss above average. We conclude that the index may be helpful in identifying healthy perimenopausal women in whom bone mass measurements should be considered.


The essential features of microorganisms and the rationale for antimicrobial therapy.

Antimicrobial agents have had a major impact on the control of most bacterial diseases; however, viral, fungal, protozoal and helminthic diseases have generally been less amenable to drug therapy. The reason for this lies in the different structural and physiological features that each group of microorganisms have. This article will outline the basic features of the various types of microorganisms, and relate these to the mode of action of commonly used antimicrobial agents.


Bond strengths of dentine bonding agents to dentine.

This study assessed comparatively the tensile bond strengths to dentine of four resin dentine bonding agents. Flat surfaces were produced in the occlusal dentine of human third molars, finished with 600-grit paper and prepared for bonding to Silux Plus composite with Gluma, Prisma Universal Bond 2, Scotchbond 2 and Tenure. After 24 hours in water and 250 thermal cycles, the specimens were loaded in tension to failure on an Instron machine. There were 20 specimens in each test group. An analysis of variance and Duncan's test showed that the bond strengths of Scotchbond 2 (22.8 +/- 7.2 MPa) and Prisma Universal Bond 2 (20.1 +/- 7.8 MPa) were similar but significantly higher than those of Tenure (14.3 +/- 5.3 MPa) or Gluma (12.3 +/- 6.4 MPa). A Weibull analysis confirmed the superiority of Scotchbond 2 and Prisma Universal Bond 2. Scotchbond 2 and Prisma Universal Bond 2 specimens failed either in an adhesive-cohesive mode, or cohesively through the composite or the dentine. It was concluded that Scotchbond 2 and Prisma Universal Bond 2 are effective and are the dentine bonding agents of choice.


Differences in time devoted to practice by male and female dentists.

Previous studies have found that female dentists work fewer hours per year than male dentists. This study examined factors which may explain the differences in hours worked per year that exist between male and female dentists in private practice. In 1988, a weighted, stratified random sample of dentists in Australia was surveyed by mailed questionnaire. There were 855 respondents (response rate = 75.5%) with 566 dentists from private practice (361 males and 205 females). Annual time devoted to dental practice was significantly lower for females, for dentists who were not the sole earner of the family income, and for dentists with young children. A significant interaction between sex of dentist and child age showed that hours per year in practice decreased only for females with young children. Hours worked per year were significantly higher among female dentists with no children, or older children. For males, hours worked remained at a higher level. The amount of time devoted to dentistry requires monitoring in the estimation and projection of capacity to supply dental services.


The risk management of infections.

Unfortunately, risk management, that is avoiding lawsuits, is a retro-active pastime instead of being pro-active. What this means is that we often take action only after a problem has manifested itself, rather than identifying potential problems and correcting them. This is, however, only human nature and occurs in most other walks of life. In dental malpractice, what appears to have been happening during the past few years in California is that plaintiff's lawyers have identified a problem and then started to sue dentists for it (and even run courses on how to sue dentists for it!), after which the profession has tried to take steps to identify the cause of the problem, and has then attempted to reduce it or eliminate it altogether. In the past, the dental malpractice companies (the equivalent of the Medical Protection Society and Medical Defense Union) were merely bystanders who paid out on claims and subsequently raised premiums accordingly. Now that most of the malpractice companies in California are actually run by (and often owned by) members of the profession, they are much more interested in getting involved at a very early stage, as soon as a potential problem is identified, in order to take action so that premiums do not rise unnecessarily.


The structure and function of the temporomandibular joint.

Although characterised by having a synovial membrane lining the nonarticulating surfaces within the joint capsule, in some ways the temporomandibular joint (TMJ) is an atypical joint. This paper highlights the differences between the TMJ and other movable joints with a description of the structure, innervation blood supply and musculature. Also included are details of how the TMJ moves--the effectors of movement and the various reflexes controlling movement of the joint.


General dental practitioners' needs for continuing education on the management of fissure caries.

A process of identifying GDPs' perceptions of their needs for continuing education on one topic area is described. The method employed a combination of two traditional approaches for assessing educational needs, the so-called 'wisemen' approach and interviews with members of the target audience. The process identified three groups of GDPs with differing educational needs. Their perceptions of their educational needs are described, and the advantages and disadvantages of the process discussed and compared with other methods of assessing educational needs. The study confirmed the importance of identifying educational needs in the development of an educational programme.


Fluoridation in Anglesey: a clinical study of dental caries in mothers at term.

A study of dental caries was carried out involving 1537 mothers who attended St David's Hospital, Gwynedd, between July 1986 and July 1987 for their confinement. The study was 'blind' in respect of residence. The mean DMFT value for mothers with continuous residence in the non-fluoridated Gwynedd mainland was 13.6 and the mean DMFT value for mothers living in the Anglesey Health Unit who had consumed fluoridated mains water from birth was 30% lower at 9.5 (P less than 0.0001). The confidence interval for the difference between means was 3.4-4.9. The samples from the two areas showed no significant differences in social class and age group structures. The percentage of Anglesey mothers with DMFT exceeding 15 was less than one-sixth of that for mainland mothers and the percentage of those with DMFT less than 6 was three times greater. The mean DMFS value for occlusal sites in premolars was 3.9 for mainland Gwynedd and for Anglesey 52% less at 1.9 (P less than 0.0001) with a confidence interval of 1.6-2.4. For smooth surface sites in posterior teeth, the difference was not as pronounced, with a mean DMFS value for mainland of 20.3 and for Anglesey 42% less at 11.8 (P less than 0.0001) with a confidence interval of 7.5-9.6. The results showed that child-bearing women continued to enjoy important benefits from water fluoridation into their early thirties.


Adenomatoid hyperplasia in the palate: another sheep in wolf's clothing.

Adenomatoid hyperplasia is a rare idiopathic non-inflammatory, non-neoplastic and benign lesion of minor salivary glands, that typically presents with a tumour-like mass in the palate. A 77-year-old patient is described.


What kind of people want to become dentists? General Dental Council Recruitment Working Party survey of first year undergraduate dental students.

Above all, the survey has provided a clear, if complex, description of the population of first year dental students: who they are and where they have come from; why they are doing the course and what they want to achieve from it. A number of specific conclusions about recruitment gaps can be drawn from the information received from the survey, namely: i) Girls at mixed-sex schools are apparently less likely to enter dentistry than their counterparts at all-girls' schools. This, however, is part of a much wider issue which encompasses the question of science versus arts choices amongst male and female pupils. ii) Some dental schools have a very high concentration of students whose home is the local region. Wider national publicity for these schools could be attempted. iii) In East Anglia, the East Midlands, Yorkshire and Humberside and the West Midlands, the number of qualified school leavers who become dental students is below average. iv) Family dentists and orthodontists are in a very strong position to encourage interested patients to enter the profession beginning at an early age, and with guidance could encourage these children towards additional sources of information and advice, such as the General Dental Council, which at the moment appear to be under-used. v) The information on dentistry provided by most careers advisers could be improved. In particular, careers teachers and form teachers/tutors are a widely contacted source of guidance but the information they were able to provide was not rated highly. University open days and residential courses are successful and might be used further.(ABSTRACT TRUNCATED AT 250 WORDS)


Undergraduate teaching in geriatric dentistry.

In the last quarter of a century the elderly population has increased rapidly and now represents 18% of the UK population. The profile of the elderly population is changing. There is a projected increase in the number of people aged 75 and over of 46.4% between the years of 1985 and 2025. The expected rise in people aged 85 and over is even more dramatic at 99.2%.


Serious professional misconduct arising out of dental anaesthesia and sedation.

This paper reviews three recent decisions of the Judicial Committee of the Privy Council on appeal from decisions of the Professional Conduct Committee of the General Dental Council, in which questions of general anaesthesia, sedation and resuscitation were raised. The recommendations of the Poswillo Report on general anaesthesia, sedation and resuscitation in dentistry of March 1990 are considered with respect to these three cases, and an assessment made as to whether or not the incidents which gave rise to them would have occurred had the recommendations been implemented. The implications of the Poswillo Report for the maintenance of professional standards of conduct by the General Dental Council in relation to the use of general anaesthesia, sedation and resuscitation are discussed.


A survey of disease changes observed on dental panoramic tomographs taken of patients attending a periodontology clinic.

Dental panoramic tomographs (DPTs) were taken consecutively of 500 patients referred to a specialist periodontal department by general dental practitioners in order to assist in the diagnosis of the severity of the periodontal disease. Analysis of these DPTs showed 316 (63.2%) of these patients to have some form of dental abnormality unrelated to periodontal disease. The DPT was shown to be a valuable screening technique for clinical practice.


Dental care of patients susceptible to infective endocarditis.

McGowan and Tuohy carried out a survey in Belfast in 1968 to identify patients with cardiac lesions susceptible to infective endocarditis. They also asked whether adequate precautions had been taken by the patients' medical and dental advisers in respect of antibiotic cover for dental surgical procedures. This survey has now been repeated in the Belfast and Glasgow Dental Schools. When compared with those of 1968, the results of these recent studies show that while more 'at risk' patients are receiving antibiotic cover for dental surgical procedures there is still room for improvement in the advice given to patients by medical and dental practitioners.


Cardiopulmonary resuscitation skills of dental personnel.

This study assessed the cardiopulmonary resuscitation (CPR) skills of 25 dental personnel. Theory was tested by multiple choice questionnaire (MCQ) and practical skills assessed using a recording Resusci-Anne manikin. The assessment was based upon the recommendations of the Resuscitation Council of the UK. Seven of the 16 dental students and six of the nine house officers tested passed the MCQ examination. All failed the practical assessment. It is concluded that more emphasis should be placed upon CPR instruction in undergraduate dental courses and that regular update courses are advisable to maintain CPR skill.


Public perceptions of the funding of NHS dental services.

A survey was carried out of 102 members of the general public, asking for their views of the recent changes in the government funding of NHS dentistry. Approximately 80% of those surveyed had heard about the changes. The majority thought that the implications of the change would be a rise in costs to patients and a fall in the number of NHS dentists.


Tooth mutilation in Angola.

In common with many countries throughout sub-Saharan Africa, some of the many tribes which comprise the indigenous population of Angola practise various forms of tooth mutilation. Three examples associated with distinctive tribes are described and compared with similar practices in neighbouring countries and their references from the literature.


Dental personnel planning and the single market: problems ahead?

Recently Whitehouse expressed concern about the possible implications of the legislation regarding the freedom of movement of labour within the European Community upon dental policy. Particular reference was made to the possibility of a major inflow of dental personnel to the United Kingdom. This paper looks at the evidence on which such worries appear to be based and examines the possibilities that this could have for planning dental personnel requirements in the UK. Dental personnel are defined in this paper as dental practitioners.


Mastication and swallowing: an overview.

The cycles of jaw and tongue movement during feeding produce not only the breakage of food but its intra-oral transport; which activity predominates depends upon the physical characteristics of the food. When hard food is eaten and tooth-food-tooth contact is made during jaw closure, the velocity of closing is suddenly reduced, producing two clearly different phases of closure; during the second phase the activity of the jaw closing muscles is much increased. Conversely, in cycles with a mainly transport function (eating soft food), the antero-posterior movements of the tongue are much greater; this alters the time and rate at which the jaw opens. The pattern of jaw movement during closing and during opening consequently varies with food consistency. The evidence suggests that sensory input controls the form of the cyclical tongue and jaw movements. However the basic plan of movement is produced by the activity of a brainstem pattern generator which receives input from both cerebro-cortical and peripheral sources. The swallow that occurs in normal feeding consists of the equivalent of the classical second stage of swallowing inserted into the occlusal or initial jaw opening phase of an otherwise standard cycle. Although leakage of traces of food or saliva into the vallecula appears to be a peripheral sensory input of major importance in inducing such a swallow, the execution of the swallow is due to a pattern generator in the brainstem.


General anaesthesia in the dental surgery: a comparison of propofol and methohexitone.

General anaesthesia was assessed in 100 dental patients in general dental practice using either propofol or methohexitone. Mean induction doses were 1.7 mg/kg and 1.5 mg/kg for propofol and methohexitone, respectively. Anaesthesia was maintained with nitrous oxide and oxygen, supplemented in the majority of cases with halothane. Both groups were comparable in relation to satisfactory surgical conditions and recovery. The maximum heart rate following induction of anaesthesia was significantly greater in the group given methohexitone. Despite the satisfactory results obtained in this study the need for full resuscitation facilities will encourage the trend towards most dental general anaesthesia taking place in a hospital environment.


Effects of the removal of composite resin restorations on Class II cavities.

Composite resin has such good aesthetic qualities that it is often difficult to identify the tooth-restoration interface, yet this is particularly important should the material require complete removal. Following the in-vitro removal of direct and indirect composite resin restorations from Class II cavities significant changes in cavity size and shape were recorded. Thirty-eight cavities were studied from both occlusal and proximal aspects and the final cavity size was compared to the original cavity. There was a significant increase in cavity size with a mean increase of 37% for the direct composite cavities and 35% for the indirect cavities, although the range of values is large. Following restoration removal, occlusal surfaces were seen to increase in 71% of teeth and proximal surfaces in 75% of teeth. There was no significant difference between the results for direct and indirect composite restorations. Occlusal dovetails and cavity undercuts were created in cavities which did not contain these features initially.


Dentistry in Poland.

A visit to the Orthodontic Institute in Warsaw was kindly sponsored by American Orthodontics in order to enable a straight wire typodont course to be conducted. The entire orthodontic department turned out for the course, and it proved to be a stimulating and enjoyable few days. This report details the state of orthodontics in Poland and aims to outline various similarities and differences between dental training in Warsaw and in Great Britain, both at undergraduate and postgraduate levels.


Concept analysis of anxiety.

Anxiety, a nursing diagnosis that impacts clients in all settings and nurses throughout the profession, is clarified through the technique of concept analysis. Uses of the concept of anxiety in prominent theories of human behavior and in nursing are reviewed. Four critical attributes occurring in all cases of anxiety are identified--model cases, a related case, a contrary case, and an illegitimate case are presented. Antecedents to anxiety are identified. Consequences of anxiety are discussed. Empirical referents that demonstrate occurrence of the concept of anxiety are determined, classified, and related to critical attributes. This concept analysis provides an essential conceptual base for instrument development and clinical research on anxiety.


MR imaging of pituitary macroadenomas before and after transsphenoidal surgery.

MR findings before and after transsphenoidal surgery were evaluated in 6 cases. T1-weighted (TR/TE 600/20) sagittal and coronal images with 2 or 4 acquisitions were obtained, using 3-mm slice thickness and 0.3-mm interslice gaps. Of 18 MR examinations, 13 included coronal i.v. contrast medium enhanced images. Image quality, sinus cavernosus invasion, identification of normal pituitary tissue and tumor size were examined. All MR studies clearly demonstrated the macroadenomas whether 2 or 4 acquisitions were used, and whether i.v. contrast medium was administered or not. Surgically confirmed sinus cavernosus infiltration was seen in 4 patients. The pituitary stalk was identified separate from the tumor in 2 patients, and the gland in one. There was reduction in tumor size over time, indicating that final radiologic assessment after transphenoidal surgery is best performed 4 to 6 months postoperatively. It should not be necessary to routinely include i.v. contrast medium injection in the postoperative evaluation of macroadenomas.


Axes: focus of taxonomy II.

A number of persistent issues in the nursing diagnosis community have challenged the ability of one nursing diagnosis taxonomy to account for nursing's practice. The North American Nursing Diagnosis Association (NANDA) Taxonomy Committee, charged with the preparation of one taxonomy for all, has struggled with some of these issues and has initiated development of axes. The issues, figuratively speaking, become the axes. The axes are intended to describe the dimensions of the human condition. This article, third in a series of four, describes the process and development of the proposed axes.


Measurements of T1 and T2 over time in formalin-fixed human whole-brain specimens.

T1 and T2 were measured in 5 formalin-fixed human whole-brain specimens as a function of time. Gray matter/white matter contrast reversal was observed around the 4th day and was considered to be due to the greater decrease in T1 in gray than in white matter. A possible explanation for this is that the decomposition of the myelin phospholipid structure by formalin somewhat counteracts the general reductive effect of the fixation procedure on relaxation times.


Gadodiamide injection and gadopentetate dimeglumine. A double-blind study in MR imaging of the CNS.

A double-blind, randomized parallel phase III study in MR imaging of the central nervous system was conducted to compare the safety and diagnostic utility of gadodiamide injection and gadopentetate dimeglumine at a dose of 0.1 mmol/kg b.w. in 60 adult patients. Seven patients in the gadodiamide injection group experienced 10 adverse events, 5 of the events possibly related to the contrast agent. In the gadopentetate dimeglumine group 5 patients reported 3 contrast agent-related adverse events out of 8 events. All events were transient and required no treatment. Seven incidents of patient discomfort, and some minor changes in vital signs and laboratory parameters were of no clinical concern. Contrast enhancement was observed in 60% and 44% of the patients with structural abnormalities in the gadodiamide injection group and gadopentetate dimeglumine group, respectively. No difference in overall efficacy was observed. Gadodiamide injection was found to be a safe and effective contrast agent.