Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.     

Effect of methemoglobin formation on the MR appearance of subarachnoid hemorrhage

Subarachnoid hemorrhage has a much higher intensity in magnetic resonance (MR) images with the passage of time. Acute subarachnoid hemorrhage is difficult to see; within 1 week its appearance has become intensified on T1-weighted images. Different concentrations of blood and lysed red blood cells in cerebrospinal fluid (CSF) were examined spectroscopically but did not significantly alter T1 and T2 relaxation of CSF acutely. Ultraviolet visible spectroscopy of bloody CSF stored hypoxically for 3 days showed the presence of methemoglobin. The iron in methemoglobin is paramagnetic; in combination with water this facilitates T1 relaxation. It is concluded that methemoglobin formation with T1 shortening at least partially accounts for the increasing intensity of the MR appearance of subarachnoid hemorrhage over time in the central nervous system and may also explain the intense appearance of subacute hemorrhage in MR images elsewhere in the body.     

High‐frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency

Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.     

In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin

Interleukin-1 alpha (IL-1 alpha) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 alpha in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 alpha at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 alpha (0.5 micrograms/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 alpha injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 alpha on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte- macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 alpha as a generalized stimulator of hematopoiesis and show that the cytokine- induced suppression of late-stage erythropoiesis can be prevented by EPO.     

Expert system-controlled image display

Conventional computer-based medical expert systems deliver advice to physicians as written text. While such advice is useful, it has distinct limitations in a visually oriented discipline such as diagnostic radiology, in which decisions often depend on pattern recognition and appreciation of subtle morphologic features. The authors developed a prototype expert computer system, IMAGE/ICON, which displays groups of images sorted into a series of axes based on different ways in which they may be similar. They may share a common feature, group of features, causes, or clinical setting. IMAGE/ICON may display examples of morphologic variations of a dominant finding or a spectrum of abnormalities seen in an specific disease or group of diseases. The system also assembles a written analysis of key features of a case. Such a tool may be useful as a diagnostic aid or for continuing medical education. It is likely to have particular impact in the form of an intelligent radiologic workstation, as picture archiving and communication systems become available.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

What are the qualitative experiences of people affected by kidney failure receiving haemodialysis?

Background

People affected by kidney failure receiving haemodialysis experience complexity within their health condition unlike any other chronic illness or condition. Kidney failure impacts the individual in all areas of their life including relationships and activities of daily living.

Objective

To conduct a meta-aggregation of studies about the lived experiences of people with kidney failure receiving haemodialysis.

Design

Using PRISMA Guidelines, six databases (CINAHL, ClinicalTrials.gov , Cochrane Library, MEDLINE, PsycINFO, and Scopus) were comprehensively searched using keywords and subject headings from January 1990 to October 2021. Articles were assessed according to prespecified eligibility criteria. Data extraction and quality appraisal was conducted. A meta-aggregation of qualitative findings was conducted using the Joanna Briggs Institute methodology for meta-aggregation.

Results

Of the 9409 articles screened, 55 studies were included. This represented a total of 188 findings across 45 categories representing a range of unmet supportive care needs. The meta-aggregation identified 11 synthesised findings broadly related to psychological/emotional needs, physical needs, social needs, interpersonal/intimacy needs, patient-clinician communication needs, family related needs, health system/information needs, spiritual needs, daily living needs, practical needs and daily living needs.

Conclusions

This meta-aggregation has identified that people affected by kidney failure can experience a range of unmet supportive care needs. It was evident that living with kidney failure and receiving haemodialysis impacted a person's sense of self, introduced practical needs and other complex needs which were not being addressed in existing services. This review has highlighted important implications for clinical practice and future research directions.