'No ordinary meeting': Robert McWhirter and the decline of radical mastectomy.

On 7 January 1948, a meeting was held at the Royal Society of Medicine in London. Its purpose was to settle a controversy. Robert McWhirter, an Edinburgh-based radiotherapist, had been invited to defend the scandalous position advocated by Geoffrey Keynes ten years previously: that radical mastectomy offered no survival advantage when compared to simple mastectomy plus local radiotherapy. The negative publicity surrounding the meeting proved overwhelming for Keynes and he abandoned his research. Indeed, the events of the meeting may have been quietly buried were it not for McWhirter who, over the following decade, pursued Keynes' research. He refined his technique, sparing patients the disfiguring and painful radical mastectomy without compromising overall survival. Later, he garnered support from other researchers, which led to a series of papers confirming his original findings. Towards the end of his career, he also made contributions to service organisation and hormone therapy, eventually holding the Presidency of the Faculty of Radiologists. By keeping the controversy alive, McWhirter was instrumental in overturning 60 years of surgical dogma. He remains a pivotal figure in the history of breast cancer.

HERSCHEL/SCORE, imaging the solar corona in visible and EUV light: CCD camera characterization.

The HERSCHEL (helium resonant scattering in the corona and heliosphere) experiment is a rocket mission that was successfully launched last September from White Sands Missile Range, New Mexico, USA. HERSCHEL was conceived to investigate the solar corona in the extreme UV (EUV) and in the visible broadband polarized brightness and provided, for the first time, a global map of helium in the solar environment. The HERSCHEL payload consisted of a telescope, HERSCHEL EUV Imaging Telescope (HEIT), and two coronagraphs, HECOR (helium coronagraph) and SCORE (sounding coronagraph experiment). The SCORE instrument was designed and developed mainly by Italian research institutes and it is an imaging coronagraph to observe the solar corona from 1.4 to 4 solar radii. SCORE has two detectors for the EUV lines at 121.6 nm (HI) and 30.4 nm (HeII) and the visible broadband polarized brightness. The SCORE UV detector is an intensified CCD with a microchannel plate coupled to a CCD through a fiber-optic bundle. The SCORE visible light detector is a frame-transfer CCD coupled to a polarimeter based on a liquid crystal variable retarder plate. The SCORE coronagraph is described together with the performances of the cameras for imaging the solar corona.

Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos.

Embryonic stem (ES) cells are pluripotent cells with the potential to differentiate into cells or tissues that may be used for transplantation therapy. Parthenogenetic ES (pES) cells have been recently derived from both mouse and human oocytes and hold promise as a cell source that is histocompatible to the oocyte donor. Because of the importance of major histocompatibility complex (MHC) antigens in mediating tissue rejection or acceptance, we examined levels of mRNA and protein expression of MHC class I proteins, as well as several MHC class I antigen processing and presentation chaperones in mouse ES cells derived from both fertilized (fES) and parthenogenetic (pES) embryos. We found that H-2K, Qa-2, TAP1, TAP2, and tapasin mRNAs were all expressed at low levels in undifferentiated and differentiating ES cells and were significantly upregulated in response to interferon-gamma (IFN-gamma) treatment following 14 days of differentiation. Likewise, expression of H-2K(b) and H-2K(k) proteins were upregulated to detectable levels by IFN-gamma after 14 days of differentiation, but Qa-2 protein expression remained low or absent. We also found that MHC class I, TAP1, TAP2, and tapasin mRNAs were all expressed at very low levels in ES cells compared with T cells, suggesting transcriptional regulation of these genes in ES cells. Calnexin, a chaperone molecule involved in other pathways than MHC expression, had mRNA levels that were similar in ES cells and T cells and was not upregulated by IFN-gamma in ES cells. Overall, ES cells derived from fertilized embryos and parthenogenetic embryos displayed remarkably similar patterns of gene expression at the mRNA and protein levels. The similarity between the fES and pES cell lines with regard to expression of MHC class I and antigen-processing machinery provides evidence for the potential usefulness of pES cells in transplantation therapy.

Genetics and imaging to assess oocyte and preimplantation embryo health.

Two major criteria are currently used in human assisted reproductive technologies (ART) to evaluate oocyte and preimplantation embryo health: (1) rate of preimplantation embryonic development; and (2) overall morphology. A major gene that regulates the rate of preimplantation development is the preimplantation embryo development (Ped) gene, discovered in our laboratory. In mice, presence of the Ped gene product, Qa-2 protein, results in a fast rate of preimplantation embryonic development, compared with a slow rate of preimplantation embryonic development for embryos that are lacking Qa-2 protein. Moreover, mice that express Qa-2 protein have an overall reproductive advantage that extends beyond the preimplantation period, including higher survival to birth, higher birthweight, and higher survival to weaning. Data are presented that suggest that Qa-2 increases the rate of development of early embryos by acting as a cell-signalling molecule and that phosphatidylinositol-32 kinase is involved in the cell-signalling pathway. The most likely human homologue of Qa-2 has recently been identified as human leukocyte antigen (HLA)-G. Data are presented which show that HLA-G, like Qa-2, is located in lipid rafts, implying that HLA-G also acts as a signalling molecule. In order to better evaluate the second criterion used in ART (i.e. overall morphology), a unique and innovative imaging microscope has been constructed, the Keck 3-D fusion microscope (Keck 3DFM). The Keck 3DFM combines five different microscopic modes into a single platform, allowing multi-modal imaging of the specimen. One of the modes, the quadrature tomographic microscope (QTM), creates digital images of non-stained transparent cells by measuring changes in the index of refraction. Quadrature tomographic microscope images of oocytes and preimplantation mouse embryos are presented for the first time. The digital information from the QTM images should allow the number of cells in a preimplantation embryo to be counted non-invasively. The Keck 3DFM is also being used to assess mitochondrial distribution in mouse oocytes and embryos by using the k-means clustering algorithm. Both the number of cells in preimplantation embryos and mitochondrial distribution are related to oocyte and embryo health. New imaging data obtained from the Keck 3DFM, combined with genetic and biochemical approaches, have the promise of being able to distinguish healthy from unhealthy oocytes and embryos in a non-invasive manner. The goal is to apply the information from our mouse model system to the clinic in order to identify one and only one healthy embryo for transfer back to the mother undergoing an ART procedure. This approach has the potential to increase the success rate of ART and to decrease the high, and undesirable, multiple birth rate presently associated with ART.

A field-expedient algorithmic approach to the clinical management of chemical and biological casualties.

Warriors on the modern battlefield face considerable danger from possible attack with chemical and biological weapons. Aggravating this danger is the fact that medical resources at the lowest echelons of care, already likely to be strained to capacity during modern conventional combat, are at present inadequate to handle large numbers of chemical or biological casualties. Complicating this problem further is the austere nature of diagnostic modalities available at lower echelons. With this in mind, and given the urgency required to adequately manage chemical and biological casualties, it is likely that such casualties will initially require significant empiric care in the absence of a definitive diagnosis. Such care under field conditions, often rendered by relatively inexperienced medical personnel, might best be provided using an algorithmic approach. We have developed such an algorithm.

Antiphospholipid antibodies, ischemic stroke in young adults, and calcium supplementation: a hypothesis.

The proper treatment of younger patients who have suffered ischemic stroke and who have no stroke risk factors other than antiphospholipid antibodies is unsettled. We propose a rationale to support adding dietary supplementation with calcium and vitamin D to the present standard regimen of anticoagulant therapy for these patients. We expect that the benefits from this additional therapy will prove additive. Proving this hypothesis will require large numbers of patients unlikely to present to any one center. The military health care system is well suited to such a study.

Delayed unilateral post-traumatic tremor: localization studies using single-proton computed tomographic and magnetic resonance spectroscopy techniques.

We present the case of a 46-year-old former U.S. Marine who developed unilateral dystonic tremor responsive to anticholinergic medications 13 years after contralateral, combat-induced head trauma. Although conventional neuroimaging techniques showed normal brain anatomy, single-proton computed tomographic scans demonstrated hypometabolism ipsilateral to the area of old trauma. Proton echoplanar spectral imaging demonstrated decreased signal in this same area on creatine imaging, which normalized on anticholinergic medication. Choline imaging on medication showed a signal void in the clinically suspected basal ganglia-thalamus region. We believe that these results indirectly suggest a trans-synaptic origin of the patient's movement disorder.

Musicians' dystonia: the case of Gary Graffman.

A professional pianist developed career-ending focal dystonia. There is a possible relationship between the pianist's syndrome and his past playing history. Although the patient has derived very little benefit from various treatment modalities, his candor regarding his impairment indirectly led to the establishment of performing arts medicine as a recognized subspecialty of occupational medicine.

Use of medical specialties in medical operations other than war: lessons from Saudi Arabia.

From the experience of a U.S. Army Air Defense Artillery "battalion-plus" task force serving a 6-month rotation in the Kingdom of Saudi Arabia, we compiled the requirements for specialty consultations on deployed personnel in the predeployment screening phase, during deployment (including both inpatient hospitalizations and medical evacuations), and immediately upon return to home station. We required a wide variety of specialty expertise. In every phase of the operation, we consulted orthopedic surgery most often. Nonsurgical and surgical specialists were consulted in roughly equal numbers. Almost every field of adult medicine was represented in our sample. The distribution of consultations across specialties differs from what would be expected in combat but is similar to that seen in the few other studies of comparable populations. Excellent host nation support allowed us to use specialty expertise to an almost ideal extent. These data represent the most complete "snapshot" that has been taken of the requirements for specialty medical consultations in a military operation other than war (MOOTW). They demonstrate that under MOOTW conditions, even a healthy Army population requires the assistance of a full panel of medical specialties. They should serve as a benchmark for planners estimating the medical specialty needs that the Army must provide. Military medicine must provide access to essentially all medical specialties for personnel deployed under MOOTW conditions, whether through host nation support, telemedicine, or medical evacuation.

Thoracic outlet syndromes: a non-surgeon's perspective for those caring for musicians.

The author reviews the history and clinical presentations of several distinct clinical conditions which together make up the group of patients referred to generally by the term 'thoracic outlet syndromes.' Although in specific cases the anatomy and pathophysiology of these patients correlate well, in most of them, those with the so-called 'disputed neurogenic' form, no such correlation has ever been proven. Thus, treatment of these patients is controversial. In the appropriately cautious management of these patients, surgical decompression of the thoracic outlet should never precede a trial of aggressive conservative therapy. This precept is particularly critical in musicians, because these patients require maximal degrees of mechanical freedom to play their instruments.

Persian Gulf illnesses: preliminary neurological impressions.

We review the initial impressions of the first 65 patients evaluated neurologically at Madigan Army Medical Center as mandated by the Comprehensive Clinical Evaluation Program of the Department of Defense for Persian Gulf veterans. No consistent patterns of neurologic disease or new neurologic syndromes emerged. Our experience suggests that full neurological evaluation of such patients without a clear history of neurological symptoms is not cost effective. Headaches and sleep difficulties were the two most frequent complaints. We suggest that sleep disorders may be underdiagnosed in active duty populations.

Endoscopic management of total ureteral occlusion and ureterovaginal fistula.

Between August 1991 and June 1994, endoureterotomy was performed in nine patients for total ureteral occlusion. Four of these patients had an associated ureterovaginal fistula. The total ureteral occlusions were iatrogenic in eight patients and the result of trauma in one. The prone split leg position was used to facilitate simultaneous antegrade and retrograde ureteroscopy in all nine patients. The "cut-to-the-light" technique was utilized in six patients and a new technique employing a fascial incising needle was used in five patients. Five patients developed ureteral strictures within 5 months of the primary procedure that were corrected endoscopically. With a mean follow-up of 22 months, all nine patients have a successful outcome. Endoscopic management of difficult urteral disease such as total urteral occlusion and ureterovaginal fistula is a useful alternative to open surgery.

Solitary late recurrence of renal cell carcinoma.

Late recurrence of renal carcinoma is an unusual manifestation of this tumor but can occur in as many as 11 percent of patients surviving ten years. We describe a case of a solitary lesion occurring in the nephrectomy scar ten years following surgery. The literature is reviewed. Aggressive surgical management is warranted in the treatment of these solitary lesions. The use of advanced imaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI) can assist greatly in the management of patients.