Primary pulmonary hypertension. Practical therapeutic recommendations.

Primary pulmonary hypertension (PPH) is a rare disease of unknown aetiology which typically results in right heart failure and death within several years of the onset of symptoms. While there is no cure for PPH, several pharmacological and surgical approaches to treatment have been developed over the past decade which proved useful in a significant proportion of patients. In particular, vasodilator therapy may produce sustained haemodynamic and symptomatic improvement in up to approximately two-thirds of patients; in the remaining patients, vasodilators may either produce no benefit or result in deterioration. The calcium channel blocking agents are the most widely used oral vasodilators; continuous intravenous infusions of epoprostenol (prostacyclin; prostaglandin I2) have been used in some patients who are refractory to oral therapy, particularly as a bridge to transplantation. While combined heart-lung transplantation has been considered the surgical procedure of choice for severe pulmonary hypertension, single lung transplantation has been performed successfully in a small number of patients, and may be the preferred approach in patients with reasonably preserved right heart function.     

Foreign-body osteitis of the metacarpal bone.

Foreign-body granulomas in the hand can appear secondary to an unrecognized foreign material. In a six-year-old boy, an extensive sterile osteitis of the second metacarpal bone appeared adjacent to a wood splinter.     

Timing of carotid endarterectomy after acute stroke

An arbitrary delay of at least 6 weeks before performing carotid endarterectomy after acute stroke has been recommended based on anecdotal reports. This prolonged interval may increase the danger of recurrent neurologic deficit before surgery. From September 1978 to September 1988, carotid endarterectomy was performed on 140 patients at variable intervals after stroke. Eleven patients had temporary stroke, which left 129 patients with neurologic symptoms that persisted for 3 weeks or had a cortical infarct on CT scanning. A prospective therapeutic protocol was applied to 82 patients admitted with acute stroke. They were observed until neurologic recovery reached a plateau, based on clinical observation by a neurologist, before performing angiography and carotid endarterectomy (group I). Forty-seven patients were not seen until after recovery from stroke was established (group II). At initial presentation, the severity of neurologic deficit was classified as mild, moderate, or severe in 31%, 58%, and 11%, respectively. Recovery before operation was registered as complete in 11%, mild residual in 66%, moderate residual in 21%, and severe residual in 2%. Group I patients (n = 82, 64%) were operated on within 6 weeks of stroke and group II (n = 47, 36%) were operated on at varying times after 6 weeks. No significant difference was found in the incidence of cerebrovascular events (1.2% vs 4.2%) and deaths (1.3% vs 2.1%) between groups I and II with respect to the timing of carotid endarterectomy, and no significant difference was found between patients operated on at 2, 4, 6, or more than 6 weeks after stroke.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xenopus Tadpole Melanophores Are Controlled by Dark and Light and Melatonin Without Influence of Time of Day

Melanophores were studied in tadpoles of the South African clawed toad, Xenopus laevis , during the first week after hatching (stages 46–49) at 25°C. The tadpoles had melanophores with dispersed melanosomes in the light and punctate melanophores in the dark in LD12:12. The melanophores remained punctate in constant dark and the melanosomes remained dispersed in constant light. Lights-out (in the light-time of LD12:12) caused the melanophores to become punctate, which occurred more quickly than the dispersion of melanosomes, which commenced when the lights were turned on (in the dark-time of LD12:12). Melanophores with dispersed melanosomes in tadpoles (in constant light) became punctate in response to a series of melatonin concentrations (0.2–5 ng/ml) in their bathing water irrespective of the time of day melatonin was administered. An image-analysis technique for assessing melanophore responses was tested.     

Malignant external otitis: insights into pathogenesis, clinical manifestations, diagnosis, and therapy

Malignant external otitis is an infection of the external ear canal, mastoid, and base of the skull caused by Pseudomonas aeruginosa. The condition occurs primarily in elderly patients with diabetes mellitus. Current theories on pathogenesis and anatomic correlations are reviewed. Severe, unrelenting otalgia and persistent otorrhea are the symptomatic hallmarks of the disease, whereas an elevated erythrocyte sedimentation rate is the only distinctive laboratory abnormality. Iatrogenic causes such as administration of broad-spectrum antibiotics and aural irrigation may play a predisposing role in high-risk populations. The disease can result in cranial polyneuropathies (with facial nerve [VII] paralysis being the most common) and death. The mainstay of treatment is administration of antipseudomonal antibiotics for four to eight weeks. Recurrence is common, and mortality remains at about 20 percent despite antibiotic therapy. Given the increasing longevity of diabetic patients, the frequency of this disease is increasing. Internists, family practitioners, and ambulatory care physicians must now be cognizant of the presenting symptoms, while infectious disease specialists and otolaryngologists need to be appraised of strides in diagnosis and therapy. The role of surgery should be minimized. Use of new diagnostic radiologic modalities and new antipseudomonal antibiotics discussed in this review should lead to improved outcome.     

The molecular genetics of the incision step in the DNA excision repair process

This review describes the evolution of research into the genetic basis of how different organisms use the process of excision repair to recognize and remove lesions from their cellular DNA. One particular aspect of excision repair, DNA incision, and how it is controlled at the genetic level in bacteriophage, bacteria, S. cerevisae, D. melanogaster, rodent cells and humans is examined. In phage T4, DNA is incised by a DNA glycosylase-AP endonuclease that is coded for by the denV gene. In E. coli, the products of three genes, uvrA, uvrB and uvrC, are required to form the UVRABC excinuclease that cleaves DNA and releases a fragment 12-13 nucleotides long containing the site of damage. In S. cerevisiae, genes complementing five mutants of the RAD3 epistasis group, rad1, rad2, rad3, rad4 and rad10 have been cloned and analyzed. Rodent cells sensitive to a variety of mutagenic agents and deficient in excision repair are being used in molecular studies to identify and clone human repair genes (e.g. ERCC1) capable of complementing mammalian repair defects. Most studies of the human system, however, have been done with cells isolated from patients suffering from the repair defective, cancer-prone disorder, xeroderma pigmentosum, and these cells are now beginning to be characterized at the molecular level. Studies such as these that provide a greater understanding of the genetic basis of DNA repair should also offer new insights into other cellular processes, including genetic recombination, differentiation, mutagenesis, carcinogenesis and aging.     

The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.

Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.     

The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem.

BACKGROUND AND PURPOSE: In intensity modulated radiotherapy (IMRT), the complexity and the number of treatment fields have expanded. This may imply that the delivery time for each fraction becomes prolonged. In a number of IMRT techniques used in the clinic, the delivery time per fraction is usually 10-15 min, sometimes more than 15 min. In studies on human skin, prolonged delivery time is shown to cause significant reduction of radiation effects compared with acute irradiation. In this paper the effect of changes in fraction delivery time was studied by in vitro irradiation of mammalian cells. MATERIAL AND METHODS: Chinese hamster fibroblasts (V79-379-A) were used for simulating clinical situations. Most experiments were performed with 2Gy/fraction with 4-h intervals in 40-60 replicates. Each fraction was divided into different subfractions, simulating the delivery of a complicated treatment. The effect of changing the delivery time for each fraction was studied. Parameters for the cell survival curve and repair kinetics were determined experimentally. The same methods were also used for large fraction sizes (8Gy). The validity of the most widely used models in the literature, all derived from linear-quadratic formalism, were tested against the experimental results. RESULTS: The effect of prolonging the fraction time for 2-Gy fractions was underestimated by the biological models. The experiments showed that 10-min prolonged delivery time gave a ratio between surviving fractions at 2Gy (S-ratio) of 1.054 with a 95% confidence interval (CI) 1.030-1.080, while the models predicted 1.007 and 1.009. Extending the fraction time to 20 min gave an S-ratio of 1.063 with CI of 1.045-1.080, while the models predicted 1.012 and 1.014. For 8-Gy fractions, there was a good agreement between predications and experimental results. The ratio between surviving fractions at 8Gy is 1.370 with CI of 1.300-1.440, while the models predicated 1.37 and 1.35. CONCLUSIONS: The effect of prolonging fraction time at conventional dose/fraction is underestimated by biological models. Prolonging the fraction time will spare tissues with a fast DNA repair. There is a risk for sparing tumours. This should be considered when IMRT technique is implemented in the clinic.     

Users' subjective evaluation of electronic vision enhancement systems

The aims of this study were (1) to elicit the users' responses to four electronic head-mounted devices (Jordy, Flipperport, Maxport and NuVision) and (2) to correlate users' opinion with performance. Ten patients with early onset macular disease (EOMD) and 10 with age-related macular disease (AMD) used these electronic vision enhancement systems (EVESs) for a variety of visual tasks. A questionnaire designed in-house and a modified VF-14 were used to evaluate the responses. Following initial experience of the devices in the laboratory, every patient took home two of the four devices for 1 week each. Responses were re-evaluated after this period of home loan. No single EVES stood out as the strong preference for all aspects evaluated. In the laboratory-based appraisal, Flipperport typically received the best overall ratings and highest score for image quality and ability to magnify, but after home loan there was no significant difference between devices. Comfort of device, although important, was not predictive of rating once magnification had been taken into account. For actual performance, a threshold effect was seen whereby ratings increased as reading speed improved up to 60 words per minute. Newly diagnosed patients responded most positively to EVESs, but otherwise users' opinion could not be predicted by age, gender, diagnosis or previous CCTV experience. User feedback is essential in our quest to understand the benefits and shortcoming of EVESs. Such information should help guide both prescribing and future development of low vision devices.