Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Ocular penetration of acyclovir and its peptide prodrugs valacyclovir and val-valacyclovir following systemic administration in rabbits: An evaluation using ocular microdialysis and LC-MS

PURPOSE: To investigate the ocular penetration of acyclovir and its prodrugs following systemic administration and to elucidate the mechanism of penetration. METHODS: Hydrophilic peptide prodrugs of acyclovir were infused intravenously in New Zealand albino rabbits over 45 min at a dose equivalent to 30 mmoles/kg acyclovir. Aqueous and vitreous humor samples were obtained utilizing ocular microdialysis and blood samples were obtained from the mid ear vein using a cannula. RESULTS: The plasma bioavailability for acyclovir, valacyclovir and val-valacyclovir were similar with area under curve values being 896.24 (+/-143.58), 776.54 (+/-197.52), 824.69 (+/-217.43) min x micromoles/L respectively. Anterior segment area under curve values were 53.70 (+/-35.58), 139.85 (+/-9.43) and 291.05 (+/-88.13) min x micromoles/L respectively while the mean residence time values were 46.47 (+/-24.94), 76.30 (+/-7.24) and 188.39 (+/-80.73) min respectively. Vitreous levels of the prodrugs were not measurable. CONCLUSIONS: The valine and valine-valine ester prodrugs of ACV penetrated the anterior segment of the eye much better than acyclovir alone, probably via a carrier mediated transport mechanism.     

Comment on ‘Predicting recurrence in axillary node negative breast cancer patients’, by Rosner and Lane

on behalf of the Nottingham Breast Unit     

Neural and musculoskeletal contributions to the development of stance balance control in typical children and in children with cerebral palsy

Studies on the development of automatic postural responses in both typically developing children and children with cerebral palsy were performed. With the appearance of "pull-to-stand" behavior, typically developing children first began to show muscle responses to platform movements in mainly the ankle muscles. With increased development, additional agonist muscles were added to the response pattern and a consistent distal to proximal sequence began to emerge. Well-organized responses were seen with the onset of independent stance and walking, along with the reduction of antagonist muscle co-activation. The older children with cerebral palsy who were pre-walkers had immature muscle activation patterns like those seen in the typically developing children at the pull-to- stand stage of development. These included disorganized muscle responses and increased frequency of coactivation of both proximal–distal and agonist–antagonist muscles. In order to determine if musculoskeletal constraints contributed to these response patterns, normal children were asked to stand in a crouched posture similar to that of children with CP. This caused postural muscle response patterns to more closely approximate those of children with spastic diplegia.     

Dynamic holographic imaging of the beating human heart

Background--Currently, the reporting and archiving of echocardiographic data suffer from the difficulty of representing heart motion on printable 2-dimensional (2D) media. Methods and Results--We studied the capability of holography to integrate motion into 2D echocardiographic prints. Images of normal human hearts and of a variety of mitral valve function abnormalities (mitral valve prolapse, systolic anterior motion of the mitral leaflets, and obstruction of the mitral valve by a myxoma) were acquired digitally on standard echocardiographic machines. Images were processed into a data format suitable for holographic printing. Angularly multiplexed holograms were then printed on a prototype holographic "laser" printer, with integration of time in vertical parallax, so that heart motion became visible when the hologram was tilted up and down. The resulting holograms displayed the anatomy with the same resolution as the original acquisition and allowed detailed study of valve motion with side-by-side comparison of normal and abnormal findings. Comparison of standard echocardiographic measurements in original echo frames and corresponding hologram views showed an excellent correlation of both methods (P<0.0001, r2=0.979, mean bias=2.76 mm). In this feasibility study, both 2D and 3D holographic images were produced. The equipment needed to view these holograms consists of only a simple point-light source. Conclusions--Holographic representation of myocardial and valve motion from echocardiographic data is feasible and allows the printing on a 2D medium of the complete heart cycle. Combined with the recent development of online holographic printing, this novel technique has the potential to improve reporting, visualization, and archiving of echocardiographic imaging.     

Laparoscopy for the confirmation and prognostic evaluation of pelvic inflammatory disease.

A presumptive diagnosis of pelvic inflammatory disease (PID) is usually made in our gynecologic clinics when obscure, acute lower abdominal pain is accompained by fever and abnormal vaginal discharge, urinary and rectal discomfort, marked tenderness of the pelvic organs to palpation, or pelvic masses. In the present study, during a 2-year period, 223 women underwent laparoscopy to confirm this diagnosis. PID was confirmed in 103 (46.2%) of the cases; other serious conditions were diagnosed in 69 (30.9%) of the cases; and no evidence of disease was found in 51 (22.9%) of the cases. The authors conclude that laparoscopy is a valuable tool in the diagnosis of PID.     

Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.

PURPOSE: The aim of this study was to evaluate a series of dipeptide monoester ganciclovir (GCV) prodrugs with the goal of improving ocular bioavailability of GCV from topical ophthalmic solutions. METHODS: Solubility, logP, pH-stability profile, permeability, interaction with corneal peptide transporter, and in vivo efficacy against herpes simplex virus type 1 (HSV-1) ocular disease in the rabbit model were studied. RESULTS: Val-Val-GCV, Tyr-Val-GCV, and Gly-Val-GCV were more stable in aqueous solution than Val-GCV, showing no measurable degradation even after 7 d at 37 degrees C, within the pH range of 1.4-5.4. Tyr-Val-GCV and Val-Tyr-GCV were the most lipophilic among the prodrugs synthesized and were predicted to have an n-octanol/water partition coefficient 33 times greater than that of GCV. All of the prodrugs had a much higher aqueous solubility than the parent drug. Transcorneal permeability of Val-GCV and Val-Val-GCV was seven- to eightfold greater than that of GCV, in the presence of a proton gradient, and was significantly decreased in the presence of Gly-Pro. Val-Val-GCV (1% w/v) provided significantly better therapeutic activity than trifluorothymidine (1% w/v) against HSV-1 epithelial keratitis and equivalent therapeutic activity against stromal keratitis in the rabbit eye model. CONCLUSIONS: Val-Val-GCV demonstrates excellent corneal permeability and chemical stability, high aqueous solubility, and substantial in vivo antiviral activity against the HSV-1.