For debate: the short report - legal and ethical implications.

At the outset of an alleged medical negligence case, it is common for medical expert witnesses to be asked to write a brief report, sometimes called a short report or a screening report. Such requests may come from solicitors acting for a claimant or for the defence. Reassurances may be offered that the opinion given will not be disclosed. However, this is very often not the case. Doctors and the instructing solicitors need to be aware of the legal and ethical implications of providing such instructions. The medical expert must be aware that their duty to the court begins from the time of receipt of a letter from a solicitor requesting such a report.

Delayed onset of Huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors.

Huntington's disease (HD) is a late onset progressive genetic disorder characterised by motor dysfunction, personality changes, dementia and premature death. The disease is caused by an unstable expanded trinucleotide (CAG) repeat encoding a polyglutamine stretch in the IT15 gene for huntingtin, a protein of unknown function. Transgenic mice expressing exon one of the human HD gene with an expanded polyglutamine region develop many features of human HD. Exposure of these mice to an "enriched" environment delays the onset of motor disorders and slows disease progression [Nature 404 (2000) 721]. We have compared the levels of receptor binding of a range of basal ganglia neurotransmitter receptors believed to be important in HD, in normal mice and R6/1 transgenic HD mice housed in either enriched or standard laboratory environments. HD mice housed in a normal environment show a loss of cannabinoid CB1 and dopamine D1 and D2 receptors in the striatum and the corresponding output nuclei of the basal ganglia. HD mice exposed to an enriched environment show equivalent loss of D1 and D2 receptors as their "non-enriched" counterparts; in contrast, the "enriched" mice show significantly less depletion of CB1 receptors. In the brains of humans diagnosed with HD cannabinoid CB1 receptors are selectively lost from the basal ganglia output nuclei prior to the development of other identifiable neuropathology [Neuroscience 97 (2000) 505]. Our results therefore show that an enhanced environment slows the rate of loss of one of the first identifiable neurochemical deficits of HD. This suggests that delaying the loss of CB1 receptors, either by environmental stimulation or pharmacologically, may be beneficial in delaying disease progression in HD patients.

Anterior cingulate cortical transplantation in transgenic Huntington's disease mice.

Huntington's disease (HD) is an autosomal dominant disorder involving progressive neurodegeneration of the corpus striatum and cerebral cortex. Transgenic mice, in which exon 1 of the human HD gene with an expanded trinucleotide repeat is expressed, develop a neurodegenerative syndrome that closely models human HD. Transplantation of wild-type donor cortex into the anterior cingulate cortex of neonatal HD mice (R6/1 line) was found to delay the onset of a specific motor deficit, rear-paw clasping. However, transplantation did not significantly enhance motor performance on a suspended horizontal rod, a behavioural measure of fine motor co-ordination. Control experiments in which the anterior cingulate cortex was resected, but no donor cortical tissue was transplanted, showed no behavioural benefit. In fact, wild-type littermate mice that also underwent this surgical resection, were found to develop motor deficits similar to those exhibited by non-resected HD mice. These results suggest that the anterior cingulate cortex is an important area of pathology in this HD model, and that therapeutic approaches to HD may need to target cortical, as well as striatal areas.

N-Acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington's disease mice.

Huntington's disease (HD) is an autosomal dominant condition involving progressive neurodegeneration, primarily the corpus striatum and cerebral cortex. We have used in vivo magnetic resonance spectroscopy (MRS) to assess specific neuronal markers in transgenic mice (R6/1 line) expressing exon I of the human huntingtin gene with an expanded CAG repeat. Levels of N-acetylaspartate (NAA), an indicator of healthy neuronal function, were significantly reduced (26%) in the corpus striatum of HD mice relative to wild-type littermates at 5 months of age. However, levels of cholines and creatine-phosphocreatine were not altered in the HD mice. Expression of dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32), was assessed by immunohistochemistry in the striatum of HD mice and found to be downregulated by 5 months and, even more dramatically, at 11 months of age. In contrast, expression of calbindin was not significantly decreased in HD mice. Our results suggest that the observed decreases in DARPP-32 and NAA may contribute to aberrant receptor signalling and neuronal dysfunction in HD.

Formation of cortical fields on a reduced cortical sheet.

Theories of both cortical field development and cortical evolution propose that thalamocortical projections play a critical role in the differentiation of cortical fields (; ). In the present study, we examined how changing the size of the immature neocortex before the establishment of thalamocortical connections affects the subsequent development and organization of the adult neocortex. This alteration in cortex is consistent with one of the most profound changes made to the mammalian neocortex throughout evolution: cortical size. Removing the caudal one-third to three-fourths of the cortical neuroepithelial sheet unilaterally at an early stage of development in marsupials resulted in normal spatial relationships between visual, somatosensory, and auditory cortical fields on the remaining cortical sheet. Injections of neuroanatomical tracers into the reduced cortex revealed in an altered distribution of thalamocortical axons; this alteration allowed the maintenance of their original anteroposterior distribution. These results demonstrate the capacity of the cortical neuroepithelium to accommodate different cortical fields at early stages of development, although the anteroposterior and mediolateral relationships between cortical fields appear to be invariant. The shifting of afferents and efferents with cortical reduction or expansion at very early stages of development may have occurred naturally in different lineages over time and may be sufficient to explain much of the phenotypic variation in cortical field number and organization in different mammals.

Intracranial tuberculous subdural empyema: case report.

OBJECTIVE AND IMPORTANCE: Many types of neurotuberculosis have been described; the most common intracranial forms are tuberculous meningitis and tuberculomas. We report a unique and as yet unreported form of neurotuberculosis, which is an intracranial tuberculous subdural empyema. CLINICAL PRESENTATION: A 59-year-old man who had been previously treated for pulmonary tuberculosis (TB) presented at our institution with a long-standing history of headaches. General and neurological examinations revealed no abnormalities. Radiography of the chest confirmed fibrotic lung changes caused by healed pulmonary TB. A cranial computed tomographic scan revealed a hypodense extra-axial collection with mass effect as well as adjacent osteitis and scalp swelling. INTERVENTION: The patient underwent craniectomy of the osteitic bone and drainage of 50 ml of fluid pus located subdurally. Microscopic examination of the bone and pus revealed tuberculous granulation tissue with numerous acid-fast bacilli identified using Ziehl-Neelsen stain. Mycobacterium TB bacillus was cultured from the pus at 42 days. The patient required two further operative procedures as well as a protracted course of anti-TB therapy. CONCLUSION: The patient eventually achieved a good recovery. We recommend surgical drainage of tuberculous subdural empyema to relieve mass effect and to obtain microbiological confirmation. Furthermore, surgical treatment should be combined with an 18-month course of anti-TB chemotherapy, during which period patient compliance should be closely monitored.

The advantages of coated titanium implants prepared by radiofrequency sputtering from hydroxyapatite.

The method used to apply hydroxyapatite to implant surfaces may affect the thickness and ultimately the physical properties of the coating. This study investigated and compared the healing rates of bone around commercially pure titanium implants and titanium implants sputter-coated from a hydroxyapatite target. Forty-five sputter-coated implants and an equal number of noncoated titanium implants were placed into 15 partially edentulated dog mandibles. The implants were removed at three time periods and were evaluated mechanically and histologically. A multiple analysis of variance indicated that the interface bond strength was statistically greater (p less than 0.01) for the sputter-coated implants. Histologic analysis of the bone-implant interface demonstrated that coated implants had nearly twice the percentage of direct bone contact compared with noncoated implants. The results indicate that implants sputter-coated from a hydroxyapatite target will accelerate the healing of bone at the implant interface.

Comparison of expandable endotracheal stents in the treatment of surgically induced piglet tracheomalacia.

Present surgical alternatives for pediatric tracheobronchomalacia are limited and associated with many potentially undesirable complications. The feasibility of different intraluminal expandable endotracheal stents for the treatment of surgically induced tracheomalacia was analyzed in 27 piglets. A potentially fatal tracheomalacia was surgically created. Either a stainless steel "zig-zag" stent or a woven polymeric stent was then implanted. Tracheal patency, mucosal function, histopathologic respiratory tract changes, and effects of the stent on esophageal motility were evaluated over a 16-week period. Piglets with steel stents uniformly experienced intense inflammation leading to tracheal dysfunction and death. Piglets with polymeric stents experienced minimal respiratory symptoms. Expandable polymeric endotracheal stents alleviate surgically induced piglet tracheomalacia, were easy to insert, allowed for tracheal growth, and reduced the need for high-risk surgical procedures with prolonged ventilatory support.

Magnesium sulfate pharmacokinetics: pregnant Capra hircus model.

A comparison of standard clinical regimens for the administration of magnesium sulfate for treatment of preeclampsia was performed in the pregnant goat model. The regimen of intravenous or intramuscular load and intramuscular maintenance championed by Pritchard was found to yield higher maternal serum levels through the first 4 hours of treatment compared with intravenous load with intravenous maintenance therapy (p less than 0.05); however, neither regimen affected the concentration of magnesium ion in the cerebrospinal fluid. Urinary excretion of magnesium and passage into the amniotic fluid were also evaluated for each route of administration and neither accounted for the disparity in serum concentrations noted during the first 4 hours of magnesium therapy.

Studies of encephalitozoonosis in vervet monkeys (Cercopithecus pygerythrus) orally inoculated with spores of Encephalitozoon cuniculi isolated from dogs (Canis familiaris).

Encephlitozoonosis was induced in 35 of 38 vervet monkeys (Cercopithecus pygerythrus). They were either directly (orally) inoculated with Encephlitozoon cuniculi or indirectly exposed to this protozoan parasite. Cell-culture-grown spores of E. cuniculi, isolated from the kidneys of dogs with natural, fatal disease, were administered orally to 29 of these monkeys. Another 5 were exposed in utero by orally infecting pregnant females, and 3 were exposed to horizontal infection by nursing infected infants. Only one was given an intravenous inoculation of spores. The disease was induced in non-gravid and late-pregnant adults, immunocompetent infants, and in infants that were immunologically compromised by parenteral steroid administration, as well as in one infant that was immunologically immature because of its premature birth. The effects of age, dosage, post-inoculation (PI) interval, passage level of the parasite in cell culture and immunological status of the host were correlated with macroscopical and microscopical lesions. The experimentally induced infection was confirmed either by reisolation of the parasite in cell culture or by observation of spores in tissue sections. Both confirmatory methods were supported by serological examination. Reisolation of the organism in primary cell culture prepared from kidneys usually resulted in more frequent isolates and larger yields of spores from infants than from adult vervets. Infection with E. cuniculi invariably induced subclinical disease. Based on histology, lesions were minimal to moderately severe, depending on age, PI interval, and immunological status of the host. Alimentary tract infections were seen histologically as early as three days PI. Subsequently, infections resulted in detectable lesions most consistently in the liver, kidneys and brain. Lesions in these organs were generally granulomatous and were similar to those found in canine encephalitozoonosis. In addition, multifocal interstitial pneumonitis and myocarditis as well as vasculitis and perivasculitis were seen in other tissues and organs. Infants had more severe and more widespread lesions than adults. Although lesions and spores were still present in the brain of one immunocompetent infant 36 weeks after initial infection, the disease in immunocompetent infants and adults is thought to be self-limiting. However, infection may persist. Immunological depression favoured increased growth and multiplication of the organism, and resulted in detection of more spores within inflammatory lesions as well as more intracellular colonies of the organism that were free of inflammatory reaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Observations on the pathology of experimental encephalitozoonosis in dogs.

Experimental transmission of canine encephalitozoonosis was effected by oral dosing of urine obtained from naturally diseased animals. Per os, intraperitoneal and intravenous routes were used to induce infection with tissue culture-grown Encephalitozoon spores which were initially isolated from the kidney of a dog with terminal disease. The infection was confirmed by a rise in the indirect immunofluorescent antibody titres, the lesions found in infected dogs and isolation of the parasite in tissue culture from an infected and immunosuppressed dog. The experimentally induced disease was invariably subclinical but the histopathological changes were similar although milder than those found in fatal natural disease. The kidney appears to be the target organ and chronic interstitial nephritis develops regularly.

Effect of folinic acid on the capacity of trimethoprim-sulfamethoxazole to prevent and treat Pneumocystis carinii pneumonia in rats.

Daily administration of 1 mg of folinic acid to immunosuppressed rats with incipient or established Pneumocystis carinii pneumonia did not impair the capacity of trimethoprim-sulfamethoxazole to either prevent or treat this disease. These observations constitute the first experimental support for the use of folinic acid to prevent or control cytopenias that occur in patients with Pneumocystis carinii pneumonia who are under trimethoprim-sulfamethoxazole treatment.

Trapping, care, and laboratory management of the silvered leaf monkey (Presbytis cristatus).

The silvered leaf monkey (Presbytis cristatus) from South Kalimantan ( Borneo ), Indonesia is a natural host for a variety of filarial nematodes including Brugia malayi and Wuchereria kalimantani . Experimental studies show that it is host for W. bancrofti, a filarial nematode causing elephantiasis in man. Presbytis cristatus is a gregarious primate of primary and secondary forests, roaming in troops of 20-30 members. Primarily a fruit and leaf eater under natural conditions, this monkey can adapt to a laboratory diet of commercial monkey chow supplemented with fruits and vegetables. Troops, led by an alpha male, immediately respond to protect their young during stressful or dangerous situations. Infants are born singly and are bright orange. Transition to the adult grey and black coloration begins three to five months after birth. Silvered leaf monkeys can be readily trapped. Initially they are aggressive and will attack but become tractable several days after capture. Reaching upward is an important feeding behavior of the silvered leaf monkey and they will not feed from the floor of the cage. In the laboratory they are nonaggressive and lend themselves to various procedures such as blood drawing and examination. Silvered leaf monkeys travel well in commercial animal transport cages. In the United Stages they are not an endangered species and can be readily imported. In Indonesia they are not protected by law and can be exported.

Experimental infection of warthos (Phacochoerus aethiopicus) with African swine fever virus.

Although there were no obvious signs of illness following experimental infection of young warthog with African swine fever virus, the animals developed viraemias between 10(2,4) and 10(3,6) HD50/ml within the first week of infection, and virus concentrations in a number of lymphatic tissues attained high levels (greater than or equal to 10(6) HD50/g). Unlike in blood, and to some extent in the spleen, virus titres in lymph nodes did not decline appreciable during the 33-day observation period, since at the end of the period lymphatic tissues from 2 warthog were still infectious for domestic pigs to which these tissues were fed.

Canine encephalitozoonosis in kennels and the isolation of Encephalitozoon in tissue culture.

The protozoan Encephalitozoon was isolated in primary kidney cultures from dogs originating from three separate outbreaks of encephalitozoonosis in kennels. The disease was characterized by a fading syndrome in young puppies with nervous signs developing in some cases. It was not possible to reproduce the clinical disease with cultured organisms in either normal dogs or dogs immunosuppressed with methylprednisolone. The organisms were, however, reisolated in primary culture from two immunosuppressed dogs but not from other experimentally infected dogs. The freezing of Encephalitozoon organisms in liquid nitrogen is described.

African swine fever: pathogenicity and immunogenicity of two non-haemadsorbing viruses.

The virulence of 2 non-haemadsorbing African swine fever virus isolates were compared with 2 haemodsorbing viruses. While 3 of these isolates usually produced acute death in pigs, 1 non-haemadsorbing virus caused either a fatal infection with an extended course, or few or no obvious signs of infection. Pigs that survived infection with the latter virus were resistant to the lethal effects of the other 3 strains as well as to a pool of 7 isolates made from Ornithodorus porcinus porcinus (senus Walton, 1964) and warthog obtained in the Northern Transvaal.