Training-induced cortical representation of a hemianopic hemifield.

BACKGROUND: Patients with homonymous hemianopia often have some residual sensitivity for visual stimuli in their blind hemifield. Previous imaging studies suggest an important role for extrastriate cortical areas in such residual vision, but results of training to improve vision in patients with hemianopia are conflicting. OBJECTIVE: To show that intensive training with flicker stimulation in the chronic stage of stroke can reorganise visual cortices of an adult patient. METHODS: A 61-year-old patient with homonymous hemianopia was trained with flicker stimulation, starting 22 months after stroke. Changes in functioning during training were documented with magnetoencephalography, and the cortical organisation after training was examined with functional magnetic resonance imaging (fMRI). RESULTS: Both imaging methods showed that, after training, visual information from both hemifields was processed mainly in the intact hemisphere. The fMRI mapping results showed the representations of both the blind and the normal hemifield in the same set of cortical areas in the intact hemisphere, more specifically in the visual motion-sensitive area V5, in a region around the superior temporal sulcus and in retinotopic visual areas V1 (primary visual cortex), V2, V3 and V3a. CONCLUSIONS: Intensive training of a blind hemifield can induce cortical reorganisation in an adult patient, and this case shows an ipsilateral representation of the trained visual hemifield in several cortical areas, including the primary visual cortex.

Retinotopic distribution of chromatic responses in human primary visual cortex.

In non-human primates at least three anatomically and functionally distinct channels convey signals from the retina to the primary visual cortex (V1). Two of these channels, the parvocellular and the koniocellular, are sensitive to chromatic contrasts and form the basis of color vision. In humans, common phylogenetic history with other primates and psychophysical experiments suggest identical retinocortical mechanisms but separate evaluation of the distinct anatomical channels has been difficult because signals are already combined in V1. We studied the spatial distribution of activation to chromatic stimuli along the two opponent chromatic axes in human V1 with multifocal functional magnetic resonance imaging. The signal strength was quantified from three experiments with stimuli up to 20 degrees eccentricity. The hypothesis was that, although the parvo- and koniocellular signals are mixed in V1, distinct distributions of signal strength would be evident. We found that whereas different conditions activated the same areas of cortex, indicating that they have identical magnification factors, the responses to red/green stimulation were stronger close to the fovea whereas the blue/yellow responses were much less diminished with increasing eccentricity. Both chromatic axes showed saturating contrast response functions. Our measure directly from human V1 is in line with earlier psychophysical studies suggesting relatively stronger parvocellular channel representation close to the fovea, and more uniform distribution of the koniocellular and achromatic channels. In addition, our study presents a way to rapidly quantify retinotopic signal transmission in distinct retinocortical pathways of individual subjects.

Multifocal fMRI mapping of visual cortical areas.

The multifocal mapping of electroretinograms and visual evoked potentials has established an important role in both basic research and in diagnostic procedures. We have developed a multifocal mapping method for fMRI, which allows detailed analysis of multiple local visual field representations in the cortex with excellent spatial resolution. Visual field was divided into 60 regions in a dartboard configuration, scaled according to the human magnification factor. Within blocks of 7 s, half of the regions were stimulated with checkerboard patterns contrast reversing at 8 reversals per second, while the other half remained inactive at uniform luminance. The subset of active regions changed with each 7-s block, according to an orthogonal design. Functional MRI was done with a 3-T GE Signa and analyzed with SPM2. A general linear model was fitted producing activation maps for each of the 60 regions, and local signal changes were quantified from V1. These activation maps were next assigned to 3D surface models of the cortical sheet, and then unfolded, using the Brain à la Carte software package. Phase-encoded retinotopic analysis of conventional design served as qualitative comparison data. With multifocal fMRI, all regions were mapped with good signal-to-noise ratio in V1, and subsets of regions showed activation in V2 and V3. This method allows rapid and direct exploration of multiple local visual responses, and is thus able to give complementary information to phase encoded mapping of retinotopic areas.

Pain during the TVT procedure performed under local anesthesia.

The aim of this study was to identify patients' reactions to pain during the TVT procedure performed under local anesthesia and to consider whether this is acceptable;to see how many patients under 70 years of age could be discharged from hospital on the day of operation; and to estimate the rate of complications. This was a prospective descriptive study of 110 unselected women operated upon with TVT plasty for urinary stress incontinence under local anesthesia. The patients all received the same oral and written information, care and advice for the perioperative period. A 100 mm non-hatched VAS scale was used, 0 mm equivalent to no pain and 100 mm indicating unbearable pain. New dose analgesia is normally given postoperatively after other surgical procedures in scores over 30 mm on the VAS scale. Eighty-eight percent of patients scored their pain reaction between 0 and 10 mm, 5% at 11-20 mm, 4% between 21 and 30 mm, 2% at 31-40 mm and 1% (1 patient) at 94 mm. Mean value was 5 mm. Seventy-one percent of the total and 85% of those over 70 years old in the stress and mixed incontinent group without prolapse went home on the day of the operation. There were 2% of bladder perforations and 4% postoperative hematomas; 94% of all patients had a residual urine volume <100 ml within 24 hours. During the procedure most patients felt no pain at all and in all cases but one local anesthesia was well tolerated and accepted. The majority of the patients without prolapse could be discharged on the day of the operation. The complication rate was low and did not affect the hospital stay.

Decreased inflammatory pain due to reduced carrageenan-induced inflammation in mice lacking adenosine A3 receptors.

Mice with a targeted disruption of adenosine A(3) receptor (A(3)AR) gene were assessed for their nociceptive threshold and for their localized inflammatory response following carrageenan injected into the hindpaw. Under basal conditions no difference was seen between A(3)AR knock-out (A(3)AR(-/-)) and wild-type (A(3)AR(+/+)) mice in nociceptive response to mechanical or heat stimuli. The antinociceptive response to the intrathecal adenosine analogue R-phenylisopropyl adenosine (R-PIA) was also unchanged in the A(3)AR(-/-) mice. In contrast, heat hyperalgesia, plasma extravasation and edema following carrageenan-induced inflammation in the hind paw were significantly reduced in A(3)AR(-/-) mice compared to the A(3)AR(+/+) controls. Thus, mice lacking A(3)AR had deficits in generating the localized inflammatory response to carrageenan, supporting a pro-inflammatory role of A(3)AR in peripheral tissues. However, no evidence for a role of A(3)AR in nociception and the antinociceptive effect of R-PIA was found.

Idiotype immunity (natural and vaccine-induced) in early stage multiple myeloma.

Idiotypic structures expressed on the myeloma immunoglobulin (Ig) protein (M-component) might be regarded as tumor-specific antigens. Naturally occurring, idiotype-specific type I T-cell immunity has been observed preferentially in patients with early stage myeloma. The idiotypic structures on the clonal myeloma B-cells (B lymphocytes and plasma cells) may serve as targets for active immunization. Vaccination using the autologous monoclonal Ig as a vaccine has conferred resistance to tumor cell challenge in murine myeloma. The autologous myeloma Ig protein was used for immunization in patients with progressive stage I and early stage II multiple myeloma. When the idiotype (emulsified in aluminium phosphate) was used alone for immunization, a weak and transient idiotype-specific T-cell response was observed with no clinical effects. In our second series, the idiotype (in alum) was combined with GM-CSF. In all five patients, a specific T-cell response was induced consisting preferentially of MHC class I restricted (CD8+) T-cells. Ig-specific CD4+ T-cells were also induced. A clinical response ( > 50% reduction of the M-component concentration) was observed in one patient. These results indicate that idiotype-specific T-cell immunity may be induced or enhanced by idiotype Ig vaccination in patients with early stage multiple myeloma, in which the tumor load is relatively low and the immune system is functionally less compromized than in patients with chemotherapy-treated, advanced stages of the disease. The use of GM-CSF seems to be mandatory for the frequency and magnitude of the induced T-cell response. The optimal route, schedule and cytokine combination for idiotype immunization remains to be established.

Impact of a vaccination campaign on adult immunity to diphtheria.

OBJECTIVES: to raise the level of immunity to diphtheria in the adult population of Stockholm by a vaccination campaign. The rationale behind the campaign, conducted during 1995-1996, was the re-emergence of epidemic diphtheria in the countries of the former Soviet Union and earlier surveys of immunity to diphtheria showing low levels of protection in adults. DESIGN AND MAIN OUTCOME MEASURES: the impact of the vaccination campaign was measured by recording the age and sex of vaccinees, the type and number of vaccine doses given and any side-effects. The effect on immunity was evaluated in 1998-1999 by measuring the neutralising antibodies in blood samples from 1863 inhabitants, chosen by random stratified sampling. Vaccines and vaccinations: three doses of diphtheria (D) or diphtheria-tetanus (DT) vaccine were given to those without documented previous vaccination; others received a booster dose. The DT vaccine, with the D component purified before toxoiding, contained 15 Lf of D and 7.5 Lf of T per ml, and was given in 0.5 ml doses for the two priming doses and 0.25 ml as booster. RESULTS: 184969 doses of D or DT vaccine were given to 99939 individuals. Of the vaccinees, 65% were 50 years of age or older and 60% were women. The highest rates of reported local reactions were 1.8-5.4% and of systemic reactions, such as fever, 0.2-0.8%. The campaign resulted in a significant increase in antitoxin concentrations in the age cohorts targeted, and especially in women, less well protected than men. CONCLUSIONS: a vaccination campaign, targeting the adult part of a population, can result in a major improvement in immunity to diphtheria with only a few and minor side-effects with a DT vaccine where the D component was purified prior to toxoiding. Extending national immunisation programmes to include adults would, however, seem preferable.

Exhaled nitric oxide among pulpmill workers reporting gassing incidents involving ozone and chlorine dioxide.

The aim of the study was to investigate whether measurement of nitric oxide in exhaled air could be used for assessing the effects of irritants on the respiratory system, in this case recurrent ozone gassing in an occupational setting. The study population comprised bleachery workers (n=56) from a Swedish pulpmill carrying out ozone-based pulp bleaching since 1992 and controls (n=39). Both groups were investigated by measuring NO in exhaled air, methacholine challenge test and answers to a questionnaire concerning history of respiratory symptoms and accidental exposure to ozone peaks. There was no significant difference in NO output between exposed subjects and controls (median 67.2 versus 55.0 nL x min(-1), p=0.64). However, among bleachery workers reporting ozone gassings, the median NO output was 90.0 nL x min(-1) compared to 58.8 nL x min(-1) among those not reporting such incidents (p=0.019). There was no relation between exhaled NO and the prevalence of respiratory symptoms or bronchial hyperresponsiveness. In a multiple regression model, only reported ozone gassings were associated (p=0.016) with NO output. The results indicate an association between previous response to ozone gassing and nitric oxide output. The increased nitric oxide output among the bleachery workers reporting peak ozone exposure may indicate that chronic airway inflammation is present. Further studies are needed to evaluate the extent to which nitric oxide can be used for biological monitoring of respiratory health effects, and to relate it to other markers of airway inflammation.

Augmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors.

Granulocyte-macrophage colony-stimulating factor is by far the most widely used hematopoietic growth factor to augment immune responses. At present, the best secured effect is as an adjuvant cytokine for vaccination. Granulocyte-macrophage colony-stimulating factor can be delivered as gene-transduced tumor cells, as plasmid DNA, or as the soluble free granulocyte-macrophage colony-stimulating factor protein. Granulocyte-macrophage colony-stimulating factor must be present at the same site as the vaccine component. Granulocyte-macrophage colony-stimulating factor may also augment the effect of therapeutic monoclonal antibodies by enhancing various effector functions such as antibody-dependent cellular cytotoxicity and amplifying an idiotypic network response (i.e., antitumor immunity). It may also be advantageous to combine granulocyte colony-stimulating factor with monoclonal antibodies (neutrophil and monocyte antibody-dependent cellular cytotoxicity) for tumor therapy. However, these growth factors might also induce immune suppression, which may hamper the contemplated effect of the growth factor. It is urgently warranted to better understand these dual effects on the immune system so that we can find optimal uses for the growth factors in various clinical settings.

Sisterhood's ordeals: shared interests and divided loyalties in Finnish wartime nursing.

The aim of this article is to highlight early Finnish nursing in a special wartime context. Occupational development of nursing is envisioned by addressing at a more general level women's mutual relationships and the opportunities and obstacles of the process of occupational development. The article debates two main issues. Establishing occupational domains was a process of selecting suitable labour force and training women morally, as well. The hierarchical order of nursing is manifested especially in the questions of auxiliary labour and the so-called amateur scare. War was still a time of romanticism with visible military and religious models, but women also struggled for their right to have rights.

Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses.

Idiotypic structures expressed on the myeloma Ig protein might be regarded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients developed an idiotype (Id)-specific T-cell immunity, defined as blood T cells predominantly secreting interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed-type hypersensitivity against the Id was not evoked. The specific IFN-gamma/IL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibility complex (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37% inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T cells recognized peptides corresponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producing IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly MHC class I-restricted type I T-cell response.

Metronidazole prophylaxis to prevent infections after total abdominal hysterectomy.

METHODS: In a randomized double-blind study, 134 patients were given 500 mg metronidazole as an intravenous infusion immediately before operation for abdominal total hysterectomy and again 8 hours later and 124 patients received placebo. RESULTS: There was more wound infection, postoperative hospitalization was longer and the sedimentation rate on the sixth postoperative day was significantly higher in the placebo group. There was no difference in postoperative temperature. Postoperative wound infections occurred in 12% in the placebo group and 6% in the metronidazole group. Eight percent in the total material had urinary tract infections, the diagnosis was based on urine cultures. CONCLUSIONS: Prophylaxis with intravenous infusion of metronidazole is recommended in total hysterectomies.

An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence.

The object was to study prospectively the results of a modified intravaginal slingplasty for the surgical treatment of female stress incontinence, carried out under local anesthesia as a day procedure. Seventy five patients with genuine stress incontinence were operated upon and followed for a 2-year period. All patients were diagnosed urodynamically to have genuine stress incontinence. Pad tests and quality of life assessments were carried out in all patients both pre- and postoperatively. There were no intra- or postoperative complications and 63 patients (84%) were completely cured throughout the 2-year follow-up period. Six patients (8%) were significantly improved, i.e. they did not loose urine apart from an occasional leakage during severe cold etc. In the remaining 6 patients (8%) no improvement was seen. These failures were obvious at the first postoperative check-up after 2 months. Thus, there were no relapses after 2 months. All but 5 patients were able to void properly directly after surgery. These 5 needed an indwelling catheter during the night directly after the operation. All 75 patients were released from the hospital the same day or the day after surgery without catheterization. Mean sick leave was 10 days and mean operation time 22 minutes. No defect healing or rejection of the sling occurred. It is concluded that the procedure described is a promising new technique for the surgical treatment of female stress incontinence. Prospective long-term studies including more patients are in progress to establish the definitive place of this technique in the clinical routine.

A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging.

OBJECTIVE: We studied the efficacy, safety, and acceptability of an estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year. STUDY DESIGN: The study was open with blind analysis of vaginal cytologic testing. In addition to gynecologic examination, subjective symptoms were assessed and vaginal pH and urinary samples (for bacteriuria) were obtained before insertion of Estring. This procedure was repeated every 3 months up to 1 year's treatment, together with requests concerning acceptability and adverse experiences. At inclusion and end of Estring treatment, vaginal smears for evaluation of cytologic results were obtained. RESULTS: Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women (< 5.5). For most variables a 90% responder rate (proportion of cured and improved patients) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy. Twenty-eight (20%) of 136 women, withdrew from the study, 8 (6%) of them because of adverse events. Three women reported vaginal bleeding, none associated with malignancy or endometrial proliferation. Ten (7%) reported vaginal irritation, and in two cases vaginal ulcers were found. About 90% did not remove the ring during any of the 3-month treatment periods, and 78% used the four consecutive rings continuously up to 1 year. The ring was given a strong preference (p < 0.001) by patients with previous experience of other administration forms. CONCLUSION: Estring represents a safe, highly effective, and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women.

A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy.

OBJECTIVE: Our purpose was to study the efficacy, safety, and acceptability of a new estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries. STUDY DESIGN: Gynecologic clinical status, vaginal pH, cytologic characteristics, and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women. RESULTS: Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently, and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women (< 5.5). Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring, as measured by the pathologist's assessment of the proliferation of the vaginal mucosa. A total of 77% of users were classified as responders, compared with 39% in the pessary group. Both treatments were well accepted. The administration of the pessary was associated with a significantly higher (p < 0.001) incidence of discomfort than that of the ring, which was given better (p < 0.001) rating by the patients at the 12-week visit. A strong preference (p < 0.001) for the ring was shown by patients with previous experience with pessaries. CONCLUSION: Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method, exhibiting advantages over treatment with estriol vaginal pessaries.

Assessment of congestive heart failure in chest radiographs. Observer performance with two common film-screen systems.

The effect of observer variations and film-screen quality on the diagnosis of congestive heart failure based on chest radiographs was studied in 27 patients. For each patient, two films were exposed, one with the Kodak Lanex Medium system and one with the Agfa MR 400 system. The films were presented to three observers who assessed the presence of congestive heart failure on a three-graded scale. The results showed no significant difference between the two systems but large systematic differences between the observers. There were also differences between the two ratings by the same observer that could not be explained by the film-screen factor. It is concluded that the choice between these two systems is of little importance in view of the interobserver and intraobserver variability that can exist within the same department.

Maximal electrical stimulation in the treatment of unstable detrusor and urge incontinence.

Ninety-one patients with unstable detrusor and urge incontinence were treated with maximal electrical stimulation. There were 17 dropouts. From the remaining 74 patients 51 were subjectively cured or significantly improved, this effect lasted for more than 6 weeks in 40. Objectively a significant decrease in frequency was found, also a significant increase in bladder volume. No effect on detrusor pressure at bladder contraction was noted.

Social care and medical aid.

One main point in today's discussion about handicapped people, and maybe especially children, in Sweden recently is that they should not be also socially and economically handicapped. Therefore the government in 1986 passed a new law, through which it was possible to put pressure on the local authorities to take more extensive responsibility for the handicapped and their social situation. But the state in itself also has this responsibility. This law is a "plus"-law. It shall add what is necessary for the individual to be able to live a life as normal as possible. This paper is a review of what effect this approach may have in a specific situation.

Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.