Gyrate atrophy of the retina: inborn error of L-ornithin:2-oxoacid aminotransferase.

Cultured fibroblasts from a patient with gyrate atrophy of the retina do not convert L-ornithine, uniformly labeled with carbon-14, to proline. This metabolic block is caused by deficient L-ornithine:2-oxoacid aminotransferase activity in the patient. Her heterozygote father has intermediate activity of this enzyme.

The impact of a contaminated city water supply on an emergency department.

In March 2007 Galway City and County's water supply was officially contaminated by cryptosporidiosis. The medical and nursing staff at the city's only Emergency Department had noted a rise in an atypical form of gastroenteritis in the preceding months. A retrospective audit of 11,723 charts from January 1st 2007 to 22nd March (day after contamination was confirmed) was performed to identify these patients. The number of potential gastroenteritis cases was 185 (incidence 1.6%), with a peak five weeks before the outbreak was confirmed. Half the patients were aged between 20 and 34. Pain (80%), nausea or vomiting (74%) and diarrhoea (66.5%) were the most frequent symptoms. The mean duration of symptoms at presentation was 2 days. Stool samples were sent for nine patients and four of these were tested for Cryptosporidium. Over a quarter (28.6%) of patients were admitted and almost three-quarters (69.7% +/- 7%) had a residential address in the affected area. Difficulty exists in the early identification of new outbreaks and many of the affected patients are not detected using routine surveillance or current capture methods.

Gyrate atrophy of the choroid and retina with hyperornithinemia: characterization of mutant liver L-ornithine:2-oxoacid aminotransferase kinetics.

Deficient activity of L-ornithine:2-oxoacid aminotransferase is associated with gyrate atrophy of the choroid and retina with hyperornithinemia, an autosomal recessive disease leading to blindness. Liver tissue from two patients contained trace activity of the enzyme. The Michaelis (Km) value of the mutant enzyme for ornithine was 200 mM, 50-fold higher than normal, but increasing the concentrations of alpha-oxoglutarate and pyridoxal 5'-phosphate to 10 times those giving maximal activity of the normal enzyme had no effect on the mutant enzyme. Substrate inhibition of the mutant could not be demonstrated at 1,000 mM ornithine concentration, whereas ornithine concentrations above 70 mM inhibited the normal enzyme. The data suggest that the abnormal L-ornithine:2-oxoacid aminotransferase in the two patients studied has an altered binding site for ornithine.

Medical students in the emergency department: how do patients view participation in clinical teaching?

A survey was carried out in the Emergency Department (ED) of a single urban Irish teaching hospital to determine patients' acceptability towards medical students and their attitudes towards participating in clinical teaching. We analysed 145 patient replies and found 45 (31%) patients with previous ED medical student contact. Amongst these, 23/45 (51%) did not have verbal consent before being seen, 8/45 (18%) experienced pressure to participate but overall 35/45 (78%) felt their experience was a positive one. When patients who did not have previous contact with medical students were included in the analysis, receptiveness to student examination and procedures remained high [119 (82%) and 102 (70%) respectively] despite almost none of the patients recalled reading information about participating in medical teaching. Up to 52% patients would vary their consent depending on the severity of their clinical complaint but the majority, 104 (81%) patients were satisfied that involving medical students would not alter their clinical care.

Glycoprotein synthesis in the adult rat pancreas. IV. Subcellular distribution of membrane glycoproteins.

Zymogen granule membranes from the rat exocrine pancreas displays distinctive, simple protein and glycoprotein compositions when compared to other intracellular membranes. The carbohydrate content of zymogen granule membrane protein was 5-10-fold greater than that of membrane fractions isolated from smooth and rough microsomes, mitochondria and a preparation containing plasma membranes, and 50-100-fold greater than the zymogen granule content and the postmicrosomal supernate. The granule membrane glycoprotein contained primarily sialic acid, fucose, mannose, galactose and N-acetylglucosamine. The levels of galactose, fucose and sialic acid increased in membranes in the following order: rough microsomes less than smooth microsomes less than zymogen granules. Membrane polypeptides were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The profile of zymogen granule membrane polypeptides was characterized by GP-2, a species with an apparent molecular weight of 74 000. Radioactivity profiles of membranes labeled with [3H]glucosamine or [3H]leucine, as well as periodic acid-Schiff stain profiles, indicated that GP-2 accounted for approx. 40% of the firmly bound granule membrane protein. Low levels of a species similar to GP-2 were detected in membranes of smooth microsomes and the preparation enriched in plasma membranes but not in other subcellular fractions. These results suggest that GP-2 is a biochemical marker for zymogen granules. Membrane glycoproteins of intact zymogen granules were resistant to neuraminidase treatment, while those in isolated granule membranes were readily degraded by neuraminidase. GP-2 of intact granules was not labeled by exposure to galactose oxidase followed by reduction with NaB3H4. In contrast, GP-2 in purified granule membranes was readily labeled by this procedure. Therefore GP-2 appears to be located on the zymogen granule interior.

Discordance of diabetic microangiopathy in identical twins.

In a pair of 19-year-old monozygotic twin girls, one developed insulin-dependent, ketosis-prone diabetes at the age of three and has required insulin for the past 16 years. Her identical twin has maintained normal oral and intravenous glucose tolerance with normal insulin release and glucagon suppression. An unequivocal hypertrophy of the muscle capillary basement membrane (1,800 +/- 148 A) was dound in the diabetic twin, while a normal thickness of 1,149 +/- 62 A was present in her nondiabetic sister. Follow-up of the present subjects and data from other discordant identical twins who have reached adulthood could determine whether muscle capillary basement membrane hypertrophy is an independent marker of genetic diabetes in adults. Discordance of diabetic microangiopathy in a pair of monozygotic twins has important implications regarding the influence of heredity and environment on diabetic microangiopathy.

Prehospital trauma management: a national study of paramedic activities.

OBJECTIVES: The benefits of prehospital trauma management remain controversial. This study aimed to compare the processes of care and outcomes of trauma patients treated by paramedics, who are trained in advanced prehospital trauma care, with those treated by ambulance technicians. METHODS: A six year prospective study was conducted of adult trauma patients attended to by the Scottish Ambulance Service and subsequently admitted to hospital. Prehospital times, interventions, triage, and outcomes were compared between patients treated by paramedics and those treated by technicians. RESULTS: Paramedics attended more severely injured patients (16.5% versus 13.9%, p<0.001); they attended a higher proportion of patients with penetrating trauma (6.6% versus 5.7%, p = 0.014) and had longer prehospital times. Patients managed by paramedics were more likely to be taken to the intensive care unit, operating theatre or mortuary, (11.2% versus 7.8%, p<0.001) and had higher crude mortality rates (5.3% versus 4.5%, p = 0.07). However, no difference in mortality between the two groups was noted when corrected for age, Glasgow coma score and injury severity score. CONCLUSIONS: This large scale national study shows that paramedics show good triage skills and clinical judgement when managing trauma patients. However, the value of the individual interventions they perform could not be ascertained. Further controlled trials are necessary to determine the true benefits of advanced prehospital trauma life support.

Cephalothoracic lipodystrophy with hypocomplementemic renal disease: discordance in identical twin sisters.

This report describes the occurrence of cephalothoracic lipodystrophy in one of 7-yr-old identical twin sisters. The affected twin had classical loss of sc fat from her face, upper arms, and trunk as well as associated hypocomplementemia, microscopic hematuria, and a borderline oral glucose tolerance test without hyperinsulinism. The unaffected twin had a normal urinalysis, serum complement, and oral glucose tolerance. Both twins, when challenged iv with LRH or TRH, showed appropriate FSH and LH or TSH and PRL responses, respectively. This report, in conjunction with another similar twin pair recently described in the German literature, makes a simple, single gene genetic etiology untenable and supports the view that cephalothoracic lipodystrophy in an acquired disease.

Failure of antiviral therapy for acquired immunodeficiency syndrome-related cytomegalovirus myelitis.

We report the first published case (to our knowledge) of histopathologically documented acquired immunodeficiency syndrome-related cytomegalovirus (CMV) myelitis in which antiviral drug therapy was administered. Despite sensitivity of the patient's CMV isolate to therapy with both ganciclovir and foscarnet, use of neither of these agents halted progression of central nervous system CMV disease. Higher doses of these drugs or combination therapy may be required to treat acquired immunodeficiency syndrome-related CMV myelitis effectively.

Approaches to the treatment of cytomegalovirus retinitis: ganciclovir and foscarnet.

Both ganciclovir, a nucleoside analogue, and foscarnet, a pyrophosphate analogue, specifically bind cytomegalovirus (CMV) DNA polymerase and inhibit CMV replication at plasma concentrations achievable with intravenous administration. The agents have similar plasma half-lives, and both are cleared solely by the kidneys. Foscarnet has a low solubility and a high degree of ionization at physiologic pH, requiring it to be administered in higher doses and larger volumes. Both drugs are administered as an initial induction regimen followed by a long-term maintenance regimen. Among patients with the acquired immune deficiency syndrome (AIDS) who have CMV retinitis, the efficacy of long-term maintenance therapy, as measured by median time to retinitis progression, appears to be similar for the two drugs. The major toxicity of ganciclovir is myelosuppression, with dose-limiting neutropenia occurring in approximately 16% and thrombocytopenia in 5% of AIDS patients. The major toxicity of foscarnet is nephrotoxicity, with dose-limiting toxicity occurring in approximately 10-23% of patients; other effects of foscarnet include hypocalcemia, which may be associated with seizure and arrhythmia. Studies in vitro indicate an additive or synergistic inhibitory effect on CMV when these two drugs are combined, suggesting that lower-dose combination regimens or higher-dose alternating regimens may result in greater efficacy with less toxicity than with either drug alone.

Angiotensin-converting enzyme in sarcoid uveitis.

The diagnosis of ocular sarcoid is presumptive in the absence of systemic disease. The association of elevated serum angiotensin-converting enzyme (ACE) levels with active systemic sarcoid has been well described. With a sensitive fluorimetric assay for ACE, we found that five of ten chronic granulomatous uveitis patients without systemic sarcoid had elevated serum ACE levels. None of ten patients with uveitis of known etiology had elevated serum ACE levels. We believe that the association of an elevated serum ACE level with chronic granulomatous uveitis suggests the diagnosis of ocular sarcoid.

Ichthyosis and neutral lipid storage disease.

Four members of a consanguineous middle eastern family had a lipid storage disease characterized by congenital ichthyosiform erythroderma, neurosensory deafness, cataracts, mild myopathy, and leukocyte vacuoles. These patients are similar to several others recently reported and represent a unique disorder of lipid metabolism. The clinical and biochemical manifestations of this lipid storage disease are reviewed. Evidence is presented that the disorder is inherited as an autosomal recessive trait, and that heterozygotes may be detected by the presence of vacuoles within circulating eosinophils.

Endothelial damage with phacoemulsification and intraocular lens implantation.

Specular microscopy was used to study the corneal endothelium in a series of patients undergoing phacoemulsification with and without intraocular lens implantation by one experienced surgeon. Cell loss after phacoemulsification alone was variable, but the mean was 18%, with a median of 11%. The patients undergoing phacoemulsification plus lens implantation showed a mean cell loss of 26%, with a median of 17%. This is considerably lower than has been reported with standard intracapsular extraction plus lens implantation. The decreased endothelial damage is attributed to the technique of inserting the lens through a small incision and maintaining an air bubble between the lens and the cornea throughout lens insertion and wound closure.

Gyrate atrophy of the retina and choroid is an inborn error of metabolism of ornithine aminotransferase.

Gyrate atrophy of the retina and choroid is an autosomal recessive progressive retinal degeneration caused by an inborn error of metabolism of ornithine aminotransferase activity. Some cases are metabolically treatable. Carrier testing and prenatal diagnosis by amniocentesis are possible.

Rapid restoration of red blood cell mass in severely anemic surgical patients who refuse transfusion.

Optimal parenteral nutritional support, concomitant with replacement doses of intravenous iron dextran injection, can be safe, effective, and lifesaving for severely anemic patients who are unable to receive blood transfusions. Six patients who had sustained massive acute blood loss and two who had severe chronic anemia received as much as 140 mL of iron dextran injection intravenously. The average initial hemoglobin level in the acute group was 5.0 g/dL (range, 2.6 to 8.4 g/dL) and increased to an average of 10.6 g/dL (range, 7.5 to 12.8 g/dL) in 23 days (range, 17 to 30 days); the hemoglobin level in the chronic group was 3.8 g/dL and increased to 10.6 g/dL over an average period of 121 days. Two total abdominal colectomies, a right transverse colectomy and fistulectomy, a pyloroplasty and vagotomy, and a highly selective vagotomy were accomplished without complications in five of the patients. There were no adverse reactions to the hematopoietic therapy.

Carbon monoxide retinopathy.

A 26-year-old man who had become comatose after having inhaled carbon monoxide developed retinal venous engorgement and peripillary hemorrhages. Retinal changes closely resembled those that accompany hypoxemia.

The cerebro-oculo-facio-skeletal syndrome.

A 3 1/2-month-old boy with the cerebro-oculo-facio-skeletal syndrome had low birth weight, microcephaly, microphthalmia, cataracts, blepharophimosis, high nasal bridge, micrognathia, kyphosis, rocker-bottom feet, and a longitudinal foot groove. The product of a consanguineous parentage, he showed marked developmental retardation, suggesting abnormal recessive inheritance.

Fluorouracil therapy for proliferative vitreoretinopathy after vitrectomy.

Fluorouracil effectively inhibits epiretinal membrane formation and traction retinal detachment after vitrectomy surgery. When 0.5 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after the intraocular injection of 200,000 cultured retinal pigment epithelial cells occurred in 12 of 12 control eyes but in only six of 14 eyes treated with fluorouracil (P less than .001). Four weeks after cell injection, eight of 12 eyes treated with fluorouracil had traction retinal detachments whereas 12 of 12 control eyes did (P less than .001). The height of the traction retinal detachment four weeks after intraocular injection of 200,000 cultured retinal pigment epithelial cells was reduced 50% in eyes treated with 0.5 mg of fluorouracil every 24 hours for seven days compared to control eyes (P less than .001). When the number of injected retinal pigment epithelial cells was increased to 400,000 cells and 1.25 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after injection occurred in 15 of 15 eyes in the control group but in none of ten eyes in the treated group. Four weeks after cell injection, eight of eight eyes in the control group and five of five eyes in the fluorouracil-treated group had detachments and the mean height of the detachments in the two groups was equal. Autoradiography of the epiretinal membranes in eyes injected with 200,000 cultured retinal pigment epithelial cells and labeled for two hours with tritiated thymidine showed that 0.8% of the epiretinal cell nuclei were labeled two weeks after cell injection but that no labeled cells were present in the fluorouracil-treated eyes. Tritiated thymidine labeling of epiretinal cells in the fluorouracil-treated eyes was first noted three weeks after the cell injection. The presence of tritiated thymidine labeling in the fluorouracil-treated eyes correlated with an increase in the number of epiretinal cells and an increase in the incidence of traction retinal detachment.

Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To report the observation that a transient vitreous inflammatory reaction may develop in the eyes of patients with acquired immunodeficiency syndrome (AIDS), cytomegalovirus retinitis, and an increased CD4+ T-lymphocyte count during treatment with antiretroviral therapy including a protease inhibitor. METHODS: We reviewed the medical records of eight patients with AIDS and cytomegalovirus retinitis who developed vitreous inflammatory reactions greater than those usually seen with this disease. RESULTS: Vitreous inflammatory reactions obscured the view of the posterior pole in all patients. No iris nodules, synechiae, glaucoma, or cystoid macular edema were observed. Six patients had unilateral cytomegalovirus retinitis, and, in each, the inflammation occurred only in the eye with cytomegalovirus retinitis. The vitreous inflammatory reactions were associated with clinically inactive cytomegalovirus retinitis in six patients, with disease reactivation in one patient, and were present at diagnosis of active disease in one patient. Cytomegalovirus retinitis has not recurred in any of these patients since their episodes of vitreous inflammation. Vitreous inflammation developed in all eight patients after a substantial increase in CD4+ T-lymphocyte counts caused by combination antiretroviral therapy. Five patients had CD4+ T-lymphocyte counts of greater than 100 cells per microl at the time the vitreous inflammatory reaction developed. No other causes of uveitis were found. CONCLUSIONS: Patients with AIDS and cytomegalovirus retinitis may develop transient intraocular inflammation associated with combination antiretroviral therapy. We believe that this inflammation reflects an improved immune response against cytomegalovirus.