Physiological analysis of simple rapid movements in patients with cerebellar deficits.

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was frequently prolonged regardless of the distance or speed of the movement. The most striking kinematic abnormality was prolonged acceleration time. The pattern of acceleration time exceeding deceleration time was common in patients but uncommon in normal subjects. The best kinematic correlate of the duration of the first agonist burst was acceleration time. Altered production of appropriate acceleration may therefore be an important abnormality in cerebellar dysfunction for attempted rapid voluntary movements.     

Pharmacy customers’ views and experiences of using pharmacies which provide needle exchange services in Aberdeen and Glasgow, Scotland

Community pharmacists contribution to the management of drug problems is considerable. As the use of illicit drugs has increased, pharmacists have come under increasing pressure to offer services to problem drug users. However, there is concern among some pharmacists that offering such services may deter other customers. There is particular concern among some pharmacists about needle exchange services. Only 9.5% of Scottish pharmacies offer needle exchange services compared to 69% which are dispensing methadone (57% of which supervise methadone consumption). Qualitative interviews were used in a purposive sample of 10 pharmacies in Scotland. Eight customers were interviewed in each pharmacy to ascertain pharmacy customers’ views on these services. The majority of customers were supportive of these services. Customers were often unaware that the pharmacy they were interviewed in was offering services for people with drug problems. Pharmacy customers were more knowledgeable about, and more supportive, of needle exchange services than they were of methadone. This was because they believed needle exchange services helped to reduce the amount of discarded needles in public places. Pharmacy customers also recognised that needle exchange helped reduce the spread of disease. These findings should be used to encourage more pharmacists to offer needle exchange services.     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

31P NMR of electrically stimulated rectus femoris muscle: an in vivo graded exercise model.

This study reports on the development of a model for studying skeletal muscle metabolism in humans using NMR spectroscopy. Graded exercise was simulated using electrical stimulation in 10 healthy, fit subjects (mean VO2max = 53 +/- 4 ml.kg-1.min-1). The effects of varying the stimulation parameters, namely, the stimulation frequency, the stimulation intensity, and the duty cycle, as well as the spectral interrogation volume, were compared using data acquired from the rectus femoris muscle. With stimulation, the inorganic phosphate to phosphocreatine concentration ratio ([P(i)]/[PCr]) and the intracellular pH both follow curvilinear relationships over the stimulation frequencies from 3 to 30 Hz, with the magnitude of the observed change related closely to stimulation intensity and duty cycle. Oxidative phosphorylation predominates at stimulation frequencies below 12 Hz, while anaerobic metabolism increases sharply above 12 Hz. Our findings show clearly the interdependence of the effects of the various stimulation parameters and emphasize the care that must be exercised in interpreting the physiological significance of the biochemical data obtained from electrical stimulation models used to study skeletal muscle metabolism.     

Surgical morbidity and mortality in one hundred and twenty-nine patients with obstructive jaundice

One hundred and twenty-nine jaundiced patients were operated upon for the relief of benign and malignant bile duct obstruction during a 10-year period, 1977-86. The overall mortality was 4.7 per cent but increased to 9.1 per cent in patients with a serum bilirubin greater than 300 mumol/l. In all, 46.5 per cent of patients had a rise in postoperative creatinine but renal dysfunction occurred in only 4.7 per cent. Wound infection developed in 3.1 per cent of patients and appeared unrelated to infected bile; 3.9 per cent of patients were treated for postoperative septicaemic episodes. The low morbidity and mortality observed suggests that preoperative biliary drainage need not be considered in routine surgical practice if simple measures to maintain urine flow and prevent postoperative sepsis are used.     

Sexual assault: review of a national model protocol for forensic and medical evaluation. New Hampshire Sexual Assault Medical Examination Protocol Project Committee.

A national hospital/community model protocol was developed for the forensic and medical examination of victims of sexual assault. This review is designed to assist states in the development of sexual assault protocols. Controversial issues were addressed, including the collection of hair evidence, the importance of semen, mandatory reporting, pregnancy testing and prophylaxis, and sexually transmitted diseases including human immunodeficiency virus. The current role of DNA profiling is reviewed. These issues at the interface of medicine, forensic science, victim advocacy, and the law are analyzed. Representatives of the medical, legal, law enforcement, victim advocacy, and forensic science communities contributed to the development of the protocols at the national and state levels. The importance of a collaborative effort is emphasized. The broad protocol goals are to minimize the physical and psychological trauma to the victim while maximizing the probability of collecting and preserving physical evidence for potential use in the legal system.     

c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression

c-Myc promotes cell growth and transformation by ill-defined mechanisms. c-myc(-/-) mice die by embryonic day 10.5 (E10.5) with defects in growth and in cardiac and neural development. Here we report that the lethality of c-myc(-/-) embryos is also associated with profound defects in vasculogenesis and primitive erythropoiesis. Furthermore, c-myc(-/-) embryonic stem (ES) and yolk sac cells are compromised in their differentiative and growth potential. These defects are intrinsic to c-Myc, and are in part associated with a requirement for c-Myc for the expression of vascular endothelial growth factor (VEGF), as VEGF can partially rescue these defects. However, c-Myc is also required for the proper expression of other angiogenic factors in ES and yolk sac cells, including angiopoietin-2, and the angiogenic inhibitors thrombospondin-1 and angiopoietin-1. Finally, c-myc(-/-) ES cells are dramatically impaired in their ability to form tumors in immune-compromised mice, and the small tumors that sometimes develop are poorly vascularized. Therefore, c-Myc function is also necessary for the angiogenic switch that is indispensable for the progression and metastasis of tumors. These findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors.