Optimizing surgical strategy in locally advanced breast cancer: a comparative analysis between preoperative MRI and postoperative pathology after neoadjuvant chemotherapy.

PURPOSE: In the treatment of breast cancer, neo-adjuvant chemotherapy is often used as systemic treatment followed by tumor excision. In this context, planning the operation with regard to excision margins relies on tumor size measured by MRI. The actual tumor size can be determined through pathologic evaluation. The aim of this study is to investigate the correlation and agreement between pre-operative MRI and postoperative pathological evaluation. METHODS: One hundred and ninety-three breast cancer patients that underwent neo-adjuvant chemotherapy and subsequent breast surgery were retrospectively included between January 2013 and July 2016. Preoperative tumor diameters determined with MRI were compared with postoperative tumor diameters determined by pathological analysis. Spearman correlation and Bland-Altman agreement methods were used. Results were subjected to subgroup analysis based on histological subtype (ER, HER2, ductal, lobular). RESULTS: The correlation between tumor size at MRI and pathology was 0.63 for the whole group, 0.39 for subtype ER + /HER2-, 0.51 for ER + /HER2 + , 0.63 for ER-/HER2 +, and 0.85 for ER-/HER2-. The mean difference and limits of agreement (LoA) between tumor size measured MRI vs. pathological assessment was 4.6 mm (LoA -27.0-36.3 mm, n = 195). Mean differences and LoA for subtype ER + /HER2- was 7.6 mm (LoA -31.3-46.5 mm, n = 100), for ER + /HER2 + 0.9 mm (LoA -8.5-10.2 mm, n = 33), for ER-/HER2+ -1.2 mm (LoA -5.1-7.5 mm, n = 21), and for ER-/HER- -0.4 mm (LoA -8.6-7.7 mm, n = 41). CONCLUSION: HER2 + and ER-/HER2- tumor subtypes showed clear correlation and agreement between preoperative MRI and postoperative pathological assessment of tumor size. This suggests that MRI evaluation could be a suitable predictor to guide the surgical approach. Conversely, correlation and agreement for ER + /HER2- and lobular tumors was poor, evidenced by a difference in tumor size of up to 5 cm. Hence, we demonstrate that histological tumor subtype should be taken into account when planning breast conserving surgery after NAC.

Tight control: a new therapeutic strategy in the management of osteoporotic patients.

BMD changes in patients under tight control (monitored at 3-month intervals with adjustment of therapy guided by bone turnover markers) and routine management (controlled once a year) were compared. After 1 year, the femoral neck BMD increased significantly in the tight control compared to the routine management group. INTRODUCTION: We intended to ascertain whether tight control (i.e., follow-up visits and bone turnover markers/BTM/and parathyroid hormone/PTH/monitoring at 3-month intervals) strategy achieves a statistically greater increase in bone mineral density over the observation period than standard follow-up care (i.e., bone densitometry at 1-year intervals, without BTM monitoring). METHODS: We studied involutional osteoporotic patients newly enrolled into chronic care. One hundred and eleven patients underwent tight control, while another 113 received routine treatment (with follow-up visits scheduled at > 1-year intervals). We compared the changes in bone mineral density reflected by the results of bone mineral density (BMD) measurements of the lumbar spine and of the left femoral neck. Statistical analyses were performed with version 22 of the SPSS software package. RESULTS: In the group of patients under tight control, baseline and follow-up median BMD values were 0.842/0.881 g/cm2 at the L1-4 vertebrae and 0.745/0.749 g/cm2 at the femoral neck. In the group under routine care, the corresponding values were 0.903/0.915 g/cm2 and 0.742/0.72 g/cm2, respectively. The relative changes of the bone mineral density of the femoral neck was significantly (p = 0.041) higher in patients under tight control than in those receiving routine care; however, BMD changes in the lumbar spine were not statistically different. CONCLUSION: Our findings suggest that adopting tight control as a new therapeutic strategy might be justified in the osteoporosis management. In fact, a greater improvement of BMD can be achieved by treatment according to these principles.

Subclinical cardiovascular disease and it's improvement after long-term TNF-α inhibitor therapy in severe psoriatic patients.

BACKGROUND: There are conflicting data on the occurrence of subclinical myocardial dysfunction in psoriatic patients and on the impact of long-term tumour necrosis factor-alpha (TNF-α) inhibitor therapy on cardiac function. OBJECTIVE: In this study, we explored whether there are any signs of subclinical cardiovascular disease (echocardiographic abnormalities) in severe psoriatic patients without clinically overt heart disease. As a second objective, the influence of long-term treatment with TNF-α inhibitors on the ventricular functions of psoriatic patients was also investigated. METHODS: Clinical and echocardiographic data from 44 psoriatic patients and 45 age- and sex-matched controls were processed. As a first step, the echocardiographic parameters of psoriatic patients obtained before anti-TNF-α treatment were compared with controls. As a second step, to detect the effect of long-term anti-TNF-α treatment on echocardiographic parameters, data of patients before and after therapy were analysed. RESULTS: The right ventricular Tei index was higher (P < 0.001), whereas the tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall peak systolic velocity were lower (P < 0.001 and P < 0.0001, respectively) in the psoriatic patients than in the controls. Following treatment with TNF-α inhibitors, TAPSE and right ventricular free wall peak systolic velocity significantly improved (P < 0.0001 for both parameters). The Tei index of both ventricles improved during biological therapy; however, this change did not reach statistical significance. CONCLUSION: Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-α therapy has a potentially beneficial effect on these signs.

The selective dopamine D3 receptor antagonist SB-277011-A significantly decreases binge-like consumption of ethanol in C57BL/J6 mice.

The authors show that the dopamine D3 antagonist SB-277011-A consistently and persistently decrease binge-like EtOH consumption at 30 mg/kg and it decreases binge-like consumption on days 3, 7, 9, and 11-13 at 15 mg/kg. These findings suggest that the brain's D3 receptor may also be involved in not only ethanol reward but binge drinking as well.

Impact of magnetic resonance-guided versus conventional radiotherapy workflows on organ at risk doses in stereotactic body radiotherapy for lymph node oligometastases.

Background and purpose: Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery. Materials and methods: For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D0.5cc and D10cc values were evaluated, focusing on bowelbag and duodenum. Results: Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D0.5cc and D10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac. Conclusions: Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning.

Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease.

OBJECTIVE: The aim of this study was to perform a quantitative and functional analysis of natural CD4+CD25(high)Foxp3+ regulatory T cells (nTregs) and CD4+IL-17+ T cells, and to assess the serum levels of proinflammatory cytokines in patients with undifferentiated connective tissue disease (UCTD) before and after 5 weeks of 0.5 µg/day alfacalcidol supplementation. METHODS: Twenty-five patients with UCTD were enrolled in an open-label trial of alfacalcidol. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed by a high-performance liquid chromatography (HPLC) method. Flow cytometry was used for the quantification of nTregs and the IL-17 expression of T-helper (Th)17 cells. The serum concentrations of cytokines interleukin (IL)-12, interferon (IFN)-γ, IL-23, IL-17, IL-6, and IL-10 were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with alfacalcidol raised 25(OH)D levels from a mean of 23.5 ± 5.6 to 34.5 ± 7.4 ng/mL (p = 0.059; NS). Alfacalcidol treatment decreased both Th1- (IL-12 and IFN-γ) and Th17-related (IL-23, IL-17, IL-6) cytokine levels in UCTD patients, while the soluble IL-10 level increased (IL-12: 156.7 ± 75.2 vs. 87.5 ± 42.1 pg/mL, p < 0.001; IFN-γ: 41.5 ± 12.0 vs. 21.7 ± 9.9 pg/mL, p < 0.001; IL-23: 385.2 ± 82.2 vs. 210.0 ± 69.3 pg/mL, p < 0.001; IL-17: 37.8 ± 9.6 vs. 17.8 ± 4.5 pg/mL, p = 0.009; IL-6: 39.4 ± 11.3 vs. 23.5 ± 6.3 pg/mL, p < 0.001, IL-10: 8.4 ± 3.0 vs. 21.4 ± 9.7 pg/mL, p < 0.001). Alfacalcidol improved the Th17/nTreg imbalance, as it inhibited the IL-17 expression of Th17 cells, and increased the number of nTregs. The alfacalcidol might increase the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25⁻ cells. CONCLUSION: Our findings support the idea that vitamin D influences the Th17/nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.

Cancer in adolescents and young adults in north Netherlands (1989-2003): increased incidence, stable survival and high incidence of second primary tumours.

BACKGROUND: Lack of survival improvement in adolescents and young adults (AYA) with cancer has led to increased awareness of this young population. DESIGN: We carried out a population-based study of incidence and survival of primary tumours and second primary tumours in patients aged 12-24 in north Netherlands. Age-specific incidence rates per 100,000 and 3-year moving means were calculated. Factors associated with incidence and survival were assessed using a Poisson model, log-rank test and multivariate Cox proportional hazards analysis. RESULTS: From 1989 to 2003 a total of 1118 patients were diagnosed. The total age-specific incidence rates per 100,000 were as follows: males: 13.4 (12-15 years), 26.9 (16-19 years) and 27.5 (20-24 years) and females: 13.9, 20.7 and 20.7. Male : female ratio was 1.32. The overall estimated annual percentage change (EAPC) in incidence was 2.15% (P < 0.01). Five-year survival was 80.8% and did not improve during the study period. With median follow-up of 5.5 years (range 0.0-16.0) in our cohort the standardized incidence ratio (SIR) of second primary tumours was 30.55 (95% confidence interval = 19.96-44.76, P < 0.05). CONCLUSIONS: The total incidence of cancer in AYA increased (EAPC = 2.15%). Survival was unchanged. The SIR of a second primary tumour in this young cohort increased 31-fold. Further research is needed to study this increasing incidence and optimise treatment outcome in these young patients.

The complex role of vitamin D in autoimmune diseases.

Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.

Focally positive margins in breast conserving surgery: Predictors, residual disease, and local recurrence.

BACKGROUND: Re-excision after breast conserving surgery (BCS) for invasive breast cancer (IBC) can be omitted for focally positive margins in the Netherlands, but this guideline is not routinely followed. Focally positive and extensively positive margins have rarely been studied separately and compared to negative margins regarding clinicopathological predictors, residual disease incidence, and local recurrence. METHODS: All females with BCS for Tis-T3, without neo-adjuvant chemotherapy between 2005 and 2014 at one university hospital were included. Clinicopathological and follow-up information was collected from electronic patient records. Index tumor samples from all patients with re-excision were reviewed by one pathologist. Margins were classified as negative (≥2 mm width), close (<2 mm width), focally positive (≤4 mm length of tumor touching inked margin), or extensively positive (>4 mm length). RESULTS: From 499 patients included, 212 (43%) had negative, 161 (32%) had close, 59 (12%) had focally positive, and 67 (13%) had extensively positive margins. Increasingly involved margins were associated with lobular type, tumor size, and adjacent DCIS in IBC patients and lesion size in purely DCIS patients. In IBC patients, 17%, 49%, and 77% had re-excision after close, focally positive, and extensively positive margins and residual disease incidence was 55%, 50%, and 70% respectively. In purely DCIS patients, 26 (65%), 13 (87%), and 16 (94%) had re-excision after close, focally positive, and extensively positive margins and residual disease incidence was 39%, 46%, and 90% respectively. CONCLUSION: Incidence of residual disease after focally positive margins was not different from close margins, but was significantly higher after extensively positive margins. We recommend quantifying extent of margin involvement in all pathology reports.

A gel-electrophoretic analysis of protein ADP-ribosylation in polyoma virus-transformed and non-transformed BHK-21/C13 fibroblasts.

We have examined a variety of conditions for solubilizing and electrophoresing cell proteins in order to define optimum conditions for studying proteins modified by ADP-ribosylation. We have identified conditions in which proteins can be quantitatively extracted from cells in an undegraded form with the protein-ADPribose linkages intact. Effective measures include boiling cells briefly (4 min) in the presence of 2% SDS and 2 M urea at pH 6.8. Both SDS and urea were present in the 6-18% gradient polyacrylamide gel matrix used for electrophoresis. Under these conditions good resolution of proteins of a wide molecular-weight range is obtained. This system has been used to compare protein ADP-ribosylation in non-transformed and polyma virus-transformed baby hamster kidney (BHK) fibroblasts, since the latter cells have a greater NAD+ ADP-ribosyltransferase activity (measured in isolated nuclei and permeabilized cells). Addition of DNAase to permeabilized BHK cells over the range 10-150 micrograms led to a progressively greater activation of transferase compared with controls. When PyY cells were used, however, maximum activation was achieved with only 10 micrograms of DNAase, further additions producing a successively smaller activation relative to control cells without added nuclease. There were also differences between these cells in response to salt. Addition of NaCl (to about 0.3 M) to BHK cells resulted in various extents of transferase activation, whereas any addition of NaCl to the incubate of permeabilized PyY cells decreased transferase activity. These different enzyme activities between this transformed and non-transformed cell line are for the most part not reflected in the protein modification profiles seen on autoradiograms of acrylamide gels after electrophoresis 32P-labelled proteins. A variety of proteins are modified and their molecular weights depend on the NA concentration in the permeabilized cell incubation. At 0.5 microM NAD+ there were two major acceptors with Mr values of 14 kDa and 30 kDa, and at 100 microM NAD+, three major acceptors, with Mr values of 19 kDa. 45 kDa and greater than 170 kDa. NAD concentrations of between 1 microM and 100 microM had no further effect on protein ADP-ribosylation profiles, except for the protein(s) of Mr greater than 170 kDa, pointing to a critical difference around 0.5-1.0 microM substrate. In some experiments, however, a difference was observed in the intensity of radioactivity in two bands. This may represent two different proteins, or a single protein modified to different extents.(ABSTRACT TRUNCATED AT 400 WORDS)

Increased protein ADPribosylation in HeLa cells exposed to the anti-cancer drug methotrexate.

DNA single-strand breaks (about 200-300 per genome) were transiently detected during the first hour when HeLa cells were incubated for up to 24 h with 100 microM methotrexate. There was an expected increase in ADPribosyltransferase activity, which reached a maximum 2-3-fold stimulation at 3 h but which was still greater than in control cells after 24 h. When hypoxanthine (25 microM) was present in the incubations together with the methotrexate the transferase was no longer activated, although basal, control levels of activity were still present. DNA strand breaks were reduced in number but were still just detectable under these conditions. Cellular NAD+ levels were mostly unaffected by the various drug treatments, except for a small transient decrease after 1 h, possibly as a result of the transferase activation. Methotrexate did not cause an increase in the rate of ADPribose degradation. Degradation of ADPribose residues labelled in a preincubation period in permeabilized cells was more extensive at pH 6.0 was a 50% loss of acid-insoluble radioactivity in 30 min at 26 degrees C. At pH 8.0 the loss did not exceed 30-35% even after 90 min incubation. The activation of the transferase is reflected in a general increase in protein ADPribosylation detected by autoradiography of 32P-labelled proteins in 6.25-18.25%T gradient acrylamide gels. There were three major acceptors with molecular masses of 17, 100 and over 100 kDa, which could be respectively a histone, a transferase-derived peptide fragment and the transferase itself. When ADPribosyltransferase was inhibited with 3-amino-benzamide DNA single-strand breaks were no longer detected. However, this had no observably signficant effect on the kinetics of loss of cell viability (from Trypan blue uptake), cell number or colony-forming ability. Similar results are observed in most cases when the activation of the transferase, resulting from the incubation of cells with methotrexate, is inhibited by hypoxanthine. We conclude from such observations that the enhanced protein ADPribosylation seen in the cells exposed to methotrexate is a direct consequence of drug-exposure, but does not have any significant influence over the course of events leading ultimately to cell death.

Suicide inhibition of monoamine oxidases A and B by (-)-deprenyl. A computer-aided solution for determining inhibition specificity.

An analytical solution to the differential equations describing the kinetics of the suicide inhibition of a two-enzyme system has been derived and the modelling of suicide inhibition of the monoamine oxidases A and B (MAO A and B, EC 1.4.3.4) by a quasi-selective agent, (-)-deprenyl, is presented as an example. A new parameter, the specificity index is defined and used in a model which describes the specific and non-specific binding of (-)-deprenyl to MAO B and MAO A, respectively. This type of analysis may be of therapeutic value by indicating optimal dosage of quasi-selective MAO B inhibitors for the treatment of Parkinson's disease.

The distribution of orally administered (-)-deprenyl-propynyl-14C and (-)-deprenyl-phenyl-3H in rat brain.

Using alternatively labelled (-)-deprenyl (3H label in the ring and 14C in the propargyl group) the distribution of the compound was studied in 15 brain regions and the plasma of rats over a period of 96 h, after oral administration of 1.5 mg/kg of (-)-deprenyl. The compound is rapidly absorbed (within 15-30 min) from the gastrointestinal tract, as indicated by its high plasma level. It penetrates to the central nervous system, where it reaches a peak level within 45-60 min. During the first 2 h in the plasma the 14C label, whilst in cerebral tissues during the whole period of the experiment the 3H tracer dominates. The difference in the ratio of 3H to 14C radioactivity (compared to the 0 time relation) develops as early as in the first 15 min, which indicates the operation of a rapid "first pass" biotransformation of the compound. Our data represent the tissue molar concentration -time curves of (-)-deprenyl calculated from both the 3H and 14C radiolabels. A ratio of 1 of the concentrations of the two tracers would indicate that the molecule remained unchanged. The changes in the ratio, therefore, suggest the formation of considerable quantities of metabolites (methylamphetamine and amphetamine) and their presence in the brain. The difference between the area under the curves (AUC0-t for 3H and AUC0-t for 14C) represents the amount of metabolites expected to be formed during the experiment. The concentration of the metabolites should be taken into account while evaluating the pharmacological effect of (-)-deprenyl. We proved earlier that a dose of 1.5 mg/kg of (-)-deprenyl completely blocks MAO-B activity in the central nervous system. The fast metabolism of the inhibitor indicates that a minor part of the orally administered (-)-deprenyl is sufficient to produce a high level of selective MAO-B inhibition in the brain.

Translocation (12;22)(p13;q12) as sole karyotypic abnormality in a patient with nonlymphocytic leukemia.

Cytogenetic analysis of unstimulated bone marrow (BM) and peripheral blood (PB) cells of a patient with clinical features of atypical chronic myeloid leukemia (CML) showed t(12;22)(p13;q12) as the sole karyotypic abnormality. Subsequent fluorescence in situ hybridization (FISH) with abl- and bcr-specific cosmids as well as chromosome 12- and 22-specific DNA libraries and Southern blot analysis confirmed that in this patient t(12;22) does not constitute a cryptic Ph variant. Recently, a few very similar cases were reported by other investigations. The possible significance of this translocation as a new cytogenetic marker for nonlymphocytic leukemia is discussed.

Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2'-methyl-MPTP.

The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP(+)-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2'CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson's disease.

Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation.

Laser photocoagulation of pig retina induced breakdown of the blood-retinal barrier, with the appearance of serum proteins in the vitreous as determined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting techniques. Vitreous from lasered eyes inhibited the proliferation of cultured retinal microvascular endothelial cells in comparison with vitreous from non-lasered control eyes, and the inhibitory effect in the lasered eyes persisted for at least seven days. Inhibition was specific for endothelial cells, since no effect was observed when retinal pericytes or Tenon's fibroblasts were the target cells. These results suggest that indirect scatter photocoagulation may induce regression of neovascularisation by causing breakdown of the blood-retinal barrier and thus releasing into the vitreous serum components which result in inhibition of retinal microvascular endothelial cell growth.

Displacement analysis of binding inhomogeneities in crude extracts of receptors.

Guidelines are given to distinguish different kinds of binding inhomogeneities of non-radiolabeled ligands in crude extracts of receptors if an appropriate 'binding analogue' of the displacers is available in radiolabeled form. Three minimal models for the simplest types of binding inhomogeneities are analysed theoretically. These models include a cooperative system (with two interacting sites on the same receptor molecule) and two non-cooperative systems (one of them with a single-site receptor having two conformational states in equilibrium and the other with two single-site receptors independent of each other). In certain cases one can distinguish these systems experimentally. Furthermore, if a group of displacers is already classified according to the above models, then dissociation constants can be determined. The quantitative comparison of these displacers on the basis of their dissociation constants is more appropriate (e.g. in Quantitative Structure Activity Relationship studies) than on the basis of their ID50 and Ki values or Hill coefficients, which is often done.

Serum-induced proliferation of retinal capillary endothelial cells is inhibited in the presence of retinal extract.

Both crude retinal extract and serum contain growth factors for retinal capillary endothelial cells (EC). This study, however, has shown that the combined presence of both crude retinal extract (bovine) and adult serum, induces profound inhibition of EC growth in vitro. EC grown under these conditions develop as sparse colonies of cells which appear to be inhibited from spreading on the fibronectin-coated surface. The extract/serum mixture is not toxic to the cells since it does not affect the viability and typical cobblestone morphology of established confluent cultures. Combinations of retinal extract with adult sera from various species exert the inhibitory effect but foetal or newborn serum is not affected by the extract. Growth inhibition is also found with crude bovine brain extract but cannot be ascribed to the presence of basic fibroblast growth factor (bFGF) or heparin in the extract, nor to a previously identified heat-labile (56 degrees C, 30 min) inhibitory factor in retinal extract. The inhibition is selective for endothelial cells in that mural cells (pericytes) remain unaffected. The nature and relevance of this inhibitory activity remains to be determined.

99m Tc-HMPAO labelled leukocyte scintigraphy in patients with rheumatoid arthritis: a comparison with disease activity.

The aim of this study was to test the applicability of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leukocyte joint scintigraphy in the assessment of disease activity in 21 patients with rheumatoid arthritis, and to compare leukocyte scintigraphy with the Disease Activity Score (DAS), a validated activity index developed by the European League Against Rheumatism (EULAR). Twenty-one patients with rheumatoid arthritis were investigated by using 99mTc-HMPAO labelled leukocyte joint scintigraphy. The clinical and laboratory data were recorded, and the DAS was calculated and compared with the scintigraphic results in each case. A relatively high DAS score (4.71+/-1.07) was found in the majority of patients. The degree of accumulation of 99mTc-HMPAO leukocytes showed no correlation with a patient's age, gender, duration of disease, use of disease modifying anti-rheumatic drugs (DMARDs), visual analogue scale (VAS), Richie index, DAS, or any laboratory parameters. In contrast, a significant correlation was found between the global regional accumulation of the labelled leukocytes of the hands and feet, and the swollen-joint count. It is concluded that radiolabelled leukocyte scintigraphy could become one of the promising methods in the assessment of disease activity in patients with rheumatoid arthritis.

A comparative study of vertical and horizontal deliveries in the presence and with the assistance of the woman's partner.

The authors are the first in Hungary to have applied the method of vertical delivery with the husband's or partner's presence in the delivery room. This is part of the authors' family-centered delivery program at the Maternity Ward of Borsod-Abauj-Zemplén County Hospital, Miskolc. A comparison of 321 births was carried out, which included 158 vertical deliveries and 163 horizontal deliveries. During both vertical and horizontal deliveries, the husband or partner was present in the delivery room. The comparison included the mother's biometrics and social characteristics, as well as the circumstances of the delivery and the clinical parameters of the newborns. Certain stages of delivery in the vertical position took a shorter period of time compared to horizontal delivery, but the differences were not significant. Episiotomies were carried out in fewer cases of vertical deliveries, and significant injuries due to the lack of an episiotomy in the case of vertical deliveries were not detected. The parameters characterizing the clinical state of the newborns were the same in both groups. The answers given to questionnaires supported the favorable psychological effects of a vertical delivery. The authors hope that vertical delivery, as a possible alternative, will find its place in obstetric practice in Hungary.