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Biomedical subjects

J Andrew

Publications and source records attributed to J Andrew.

At least 19 recordsLinked to original sources

Interferon treatment for chronic hepatitis C infection in hemophiliacs--influence of virus load, genotype, and liver pathology on response.

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

Adolescent

Interstitial class II-positive cell depletion by donor pretreatment with gamma irradiation. Evidence of differential immunogenicity between vascularized cardiac allografts and islets.

We used an allograft pretreatment regimen involving lethal total-body gamma irradiation of donor rats eight days prior to transplantation to compare directly the immunogenicty of immediately-vascularized heart allografts with isolated, neovascularized pancreatic islet allografts. TBI pretreatment of heart donors (IHT) caused a modest prolongation in cardiac allograft survival compared with controls in a low-responding fully-allogeneic strain combination, Lewis-to-ACI. The addition of 10(5) donor-type dendritic cells (DCs) at the time of transplantation reversed the prolongation of IHT in this strain combination. Donor pretreatment with TBI did not lead to prolonged cardiac allograft survival in either a high-responding combination, ACI-to-Lewis, or in an MHC class II-compatible strain combination, F344-to-Lewis. In contrast, islets from irradiated donors (IIT) showed markedly prolonged survival in both low-responding (Lewis-to-ACI) and high-responding (W/F-to-Lewis) strain combinations. The addition of 10(5) donor-type DCs to the islets at the time of transplantation caused the rejection of only two of six IIT in the Lewis-to-ACI combination. Combined pretreatment regimens involving TBI-pretreated cardiac allografts--such as recipient immunosuppression with peritransplant cyclosporine (10 mg/kg on days 0, 1, and 2) or the combination of TBI (1000 cGy on day -3) and cyclophosphamide (300 mg/kg on day -5) in a pretreatment regimen--did not lead to synergistic graft prolongation in the low-responding Lewis-to-ACI combination. Immunohistologic studies showed that eight days after TBI rat hearts and islet were both greater than 90% depleted of class II (0X6+) interstitial dendritic cells while class I (0X18+) expression was unchanged. IIT are able to increase class II expression when donors are treated with recombinant gamma interferon (4000 U/day on days -3, -2, and -1). MLR data showed that ACI recipients of Lewis IIT reacted normally to donor (Lewis) and third-party (W/F) stimulator cells greater than 100 days after transplantation. The apparent greater immunogenicity of heart allografts as compared with islets in this model could be due to (1) a quantitative difference between the number of residual class II-positive cells in hearts and islets or a greater nnon-MHC antigenic load in the heart grafts given its larger size, or (2) a quanlitative difference between hearts and islets due to the presence of a vascular endothelium in the immediately vascularized heart that can present alloantigen and provide a major stimulus to rejection.

Animals

Mid-infrared lasers for endoscopic surgery. A new class of surgical lasers.

Unlike the Nd:YAG, the CO2 laser produces well circumscribed tissue removal with little unwanted damage because of its high absorption coefficient relative to tissue water. Unfortunately, conventional quartz fibers cannot transmit wavelengths greater than three microns, well below the ten micron wavelength of the CO2 laser. Thus, fiberoptic transmission of CO2 laser requires use of exotic materials that lack the excellent properties of quartz fibers and that, in some cases, are toxic or chemically unstable. However, there are large peaks in the infrared absorption curve of water in the two to three micron region. Lasers that operate in this mid-infrared region should permit CO2-like precision of cutting, along with excellent transmission through quartz fiberoptics. Two mid-infrared lasers with a fiberoptic delivery system, the Er:YAG (2.94 micron) and the Tm-Ho-Cr:YAG (2.15 micron) have been evaluated with human colon tissue in vitro and with rabbit gastric tissue in vivo. Histologic sections reveal excellently well localized lesions with minimal underlying thermal damage. Depth of penetration is controllable and occurs in very small increments. There is little spreading of the lesions at the 24 hour mark resulting from secondary thermal damage. Based on these facts, the authors think that these lasers will be of benefit to endoscopic surgeons.

Animals

Preliminary evaluation of a pulsed 2.15-micron laser system for fiberoptic endoscopic surgery.

There is a need for lasers that are compatible with fiberoptic endoscopes and that provide greater cutting precision than currently can be produced by the widely used Nd:YAG (1.06 micron) laser. Recently available lasers that operate in the 2-micron region fill this need. This laser light energy can be transmitted by low OH- silica fibers and has much less tissue penetration than radiation at 1.06 micron. We have been evaluating a prototype solid state laser system that produces pulses of 2.15 microns light that is delivered by a silica based fiberoptic delivery system with negligible transmission losses. This system is based on a thulium-holmium-chromium doped YAG (Tm-Ho-Cr: YAG) rod that lases at 2.15 micron. The laser does not require cryogenic cooling, toxic gases, or custom utilities and should be practical in a clinical environment. In vivo animal testing of this laser confirms that it provides greater ablating precision than does the Nd:YAG laser at 1.06 micron.

Animals

Occult cerebral arteriovenous malformations.

Angiographically occult arteriovenous malformations in the brain are rare but cause considerable diagnostic difficulty. Four personal cases are presented in which CT scans showed hypodense lesions with minimal or no enhancement, and angiograms showed only an avascular mass. Gliomas, a dermoid and an infarct were suspected before histological examination of biopsies or excised specimens. The patients had presented in early adult life with epilepsy and focal deficits.

Adult

The trometamol salt of fosfomycin: microbiological evaluation.

The spectrum of activity of fosfomycin and its pharmacological behaviour make it an attractive candidate for the oral treatment of uncomplicated urinary tract infection. Various factors affect the antibacterial activity so that results in different culture media vary widely. The highest activity was displayed in Eugonbroth and such results correlated well with those obtained in pooled human urine. The activity was enhanced in acid conditions such as commonly exist in infected urine. Glucose-6-phosphate potentiated the activity of fosfomycin against Escherichia coli and some other bacteria when tested in Eugonbroth (but less predictably in human urine) and the potentiating effect may be necessary in order to obtain therapeutically meaningful results in susceptibility tests. Experiments in an in vitro model of the treatment of bacterial cystitis (carried out in the absence of glucose-6-phosphate) indicated that both sensitive and 'resistant' strains of E. coli respond to concentrations of fosfomycin achievable by high-dose oral therapy with the trometamol salt. Resistance did not emerge in previously sensitive strains (or in one of the 2 'resistant' strains), providing a high peak level of antibiotic was achieved.

Culture Media

Hypoglossal-facial nerve anastomosis: a clinical and electrophysiological follow-up.

Eight patients with acoustic neuroma and five patients with hemifacial spasm, who had undergone hypoglossal-facial nerve anastomosis 1-14 years previously, were reviewed clinically and electrophysiologically with an electrically elicited blink reflex. Functional recovery from the anastomosis, as rigorously judged on a scale of good, fair and poor, was fair to poor. Electrically it was found that the blink reflex was present in eight patients, suggesting facial nerve re-innervation of the facial musculature. This was confirmed by the mild recurrence of hemifacial spasm in four patients. Implications for the future role of this operative procedure are discussed.

Facial Muscles

Pituitary apoplexy and haemorrhage into adenomas.

A review of 78 cases of surgically managed pituitary adenomas revealed that haemorrhage had occurred in 13. Frank haemorrhage or haemorrhagic infarction caused increasing headache, drowsiness, diplopia and visual failure. The correct diagnosis was suggested by skull X-rays and contrast studies leading to prompt surgical decompression.

Adenoma

Sacral sparing with cauda equina compression from central lumbar intervertebral disc prolapse.

Sparing of sensation in sacral dermatomes and of sphincter control was found in eight out of fourteen cases of severe cauda equina compression from massive central lumbar disc prolapse. Although the triangular shape of the lumbar spinal canal may be one factor for this it was found from a necropsy model that the increase in linear strain on the stretched roots of the cauda equina is least in the more centrally placed lower sacral roots. It is argued that the lower tension in these roots is determined by Young's Modulus.

Adult

Germinoma of the pituitary gland; a report of two cases.

Intracranial germinomas are usually situated in the pineal, but sometimes they arise in the infundibular region of the third ventricle (ectopic pinealoma) and may rarely extend down into the pituitary fossa. Two cases of germinoma arising within the pituitary gland and presenting with hypopituitarism, are described; no report of any similar cases could be found.

Adolescent

Stereotaxic thalamotomy in 55 cases of dystonia.

The results of stereotaxic thalamotomy in 55 cases of dystonia are presented. The 16 cases with generalized dystonia were of varied pathogenesis, only 7 being typical of the idiopathic form of adolescent onset. Four of the 16 cases benefited considerably, but the others showed little or no lasting improvement. These results are in contrast to those obtained by Cooper (1976). Of the 27 cases with segmental or focal dystonia, 22 had spasmodic torticollis; 16 of these had bilateral thalamotomies, and 62 per cent were much improved. The incidence of operative complications, in particular dysarthria, was high following bilateral lesions. The incidence of hemiparesis, known to have persisted for more than a year, was 15 per cent. This complication was as frequent in those with unilateral as with bilateral thalamotomies. The incidence of dysarthria in those without preoperative bulbar dystonia was much higher in those who had bilateral lesions (56 per cent) as compared with those who had unilateral lesions (11 per cent). The group that has been identified as benefiting greatly from stereotaxic surgery comprises those with hemidystonia following unilateral brain damage. In these patients, symptomatic improvement in abnormal movement is striking and the incidence of operative side effects from unilateral lesions is low.

Dysarthria

Epidemic of hospital-acquired infection due to methicillin-resistant Staphylococcus aureus in major Victorian hospitals.

During 1979, the Victorian Health Commission received reports of a rising proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from an increasing number of institutions. At least 31 metropolitan hospitals were involved, and six of these reported MRSA totaling between 20% and 40% of all Staph. aureus isolates. Since that time, the problem has continued. In some university teaching hospitals, strains of MRSA now cause from 200 to 300 new cases of hospital-acquired infection each year. Sepsis occurs mainly in patients who underwent surgery, premature neonates and in the immunocompromised or debilitated patients. The organism involved is multiresistant. Recent isolates show increasing resistance, particularly against gentamicin, chloramphenicol and, more lately, fusidic acid and rifampicin. Only vancomycin can be relied upon for empirical treatment. There is concern that increasing use of vancomycin will select vancomycin-resistant strains of MRSA, so that, in the near future, there may no longer be any effective antibiotic therapy against hospital staphylococci.

Australia

Tremor after head injury and its treatment by stereotaxic surgery.

Tremor, both postural and kinetic may be a late complication for victims of severe closed head injury, especially in the young, and may add to their disability. The nature of the tremor is described in eight patients. In each a stereotaxic thalamotomy was performed, dramatically relieving or reducing the severity of tremor in each instance, and resulting in improved function of the affected limb and increased independence. The site of the responsible lesion, which is thought to lie in the mid brain, is discussed together with the indications and contraindications for surgical management.

Adolescent