Induction of MHC class II expression in recipient tissues caused by allograft rejection

MHC class II antigens (DR) are not commonly expressed on parenchymal cells of kidney and liver except when they are allografts undergoing rejection. The objective of this study was to determine whether allograft rejection can also induce DR upregulation in parenchymal cells of autologous recipient organs. Dogs had unilateral renal autografts to facilitate kidney sampling. All kidneys were tubular cell DR-negative. After 8-14 days each dog received a tubular cell DR-negative allograft. Tubular cell DR became positive in both allograft and autograft simultaneously, its onset and intensity correlating with blast cell infiltration and rejection in the allograft. Blast cells were first detected in the autograft after allograft nephrectomy, and then disappeared as autograft tubular cell DR diminished over the next 6-8 days. This was reproduced on repeat allografting. In 2 untreated dogs hepatocytes became positive on day 4, with no hepatic blast infiltrate. Four other dogs received cyclosporine immunosuppression. Allograft and autograft tubular cell DR, and hepatocyte DR, increased in all dogs, but were delayed while on CsA until onset of rejection despite transient earlier allograft blast infiltration. Downregulation in autograft and liver occurred together after allograft nephrectomy. An interferon-like substance appeared in plasma after allografting in association with the DR changes in native kidney and liver. Renal allorejection therefore induces upregulation of parenchymal DR expression in autologous liver and kidney of the recipient. It is probably mediated by an interferon-like substance derived from cells infiltrating the allograft. The effect is modified by CsA.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Efficacy of the dorsal pedal bypass for limb salvage in diabetic patients: short-term observations

Limbs of diabetic patients with distal tibial disease are frequently considered unreconstructible; however, when studied with intraarterial digital subtraction angiography, the dorsal pedal artery is frequently found to be patent. We have reviewed our recent experience with 96 patients, 94% of whom had diabetes and had 97 bypasses placed to the dorsal pedal artery. All procedures were for limb salvage. Superimposed infection was present in 42.3%. In 92 instances where intraarterial digital subtraction angiography successfully visualized the dorsal pedal artery, 91 bypasses were placed. In 12 other cases where the dorsal pedal artery was not visualized by intraarterial digital subtraction angiography but audible with the continuous-wave Doppler, bypasses were completed successfully in six. All procedures were performed with vein. Inflow was taken from the femoral artery in 48, popliteal artery in 45, tibial artery in 2, and from a femoral tibial graft in 2. Perioperative mortality was 1.92%. Actuarial graft patency, limb salvage, and patient survival were 82%, 87%, and 80%, respectively at 18 months. We conclude that bypass grafting to the dorsal pedal artery can be reliably performed with acceptable short-term results. An attempt should always be made to visualize the foot vessels angiographically, especially in diabetic patients, so that this valuable option in arterial reconstruction will not be overlooked.     

Role of oxidants in microbial pathophysiology.

Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical, hypohalous acid, and nitric oxide) are involved in many of the complex interactions between the invading microorganism and its host. Regardless of the source of these compounds or whether they are produced under normal conditions or those of oxidative stress, these oxidants exhibit a broad range of toxic effects to biomolecules that are essential for cell survival. Production of these oxidants by microorganisms enables them to have a survival advantage in their environment. Host oxidant production, especially by phagocytes, is a counteractive mechanism aimed at microbial killing. However, this mechanism may be contribute to a deleterious consequence of oxidant exposure, i.e., inflammatory tissue injury. Both the host and the microorganism have evolved complex adaptive mechanisms to deflect oxidant-mediated damage, including enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the formation of reactive oxidant species in vivo and how they mediate many of the processes involved in the complex interplay between microbial invasion and host defense.     

Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.

An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.     

A comparison between fast and conventional spin-echo in the detection of multiple sclerosis lesions

Long repetition time (TR) spin-echo (SE) with T₂- or proton density weighting is the sequence of choice to detect the brain lesions of multiple sclerosis (MS). Fast spin-echo (FSE) permits the generation of T₂-weighted images with similar contrast to SE but in a fraction of the time. We compared the sensitivity of FSE and SE in the detection of the brain lesions of MS. Six patients with clinically definite MS underwent brain imaging with both dual echo (long TR, long and short echo time (TE) SE and dual echo FSE. The SE and FSE images were first reviewed independently and then compared. A total of 404 lesions was detected on SE and 398 on FSE. Slightly more periventricular lesions were detected using SE than FSE (145 vs 127), whereas more posterior cranial fossa lesions were detected by FSE (77 vs 57). With both SE and FSE the short TE images revealed more lesions than the long echo. These results suggest that FSE could replace SE as the long TR sequence of choice in the investigation of MS.     

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

Localized cerebral proton MR spectroscopy in HIV infection and AIDS.

PURPOSETo document differences in the cerebral proton MR spectra of patients with early and late stages of human immunodeficiency virus (HIV) infection.METHODWe studied the relative N-acetyl-aspartate (NAA) levels by localized proton spectroscopy of the parietooccipital region of the brain in 43 HIV-seropositive patients, including 26 with an acquired immunodeficiency syndrome (AIDS)-defining diagnosis, and in eight control subjects.RESULTSReduced relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1-associated cognitive/motor complex against neurologically healthy patients (P < .007); 3) with encephalopathic changes on MR against those with normal imaging (P < .001); and 4) on follow-up against their results on initial study (P < .03).CONCLUSIONSBy clinical (Centers for Disease Control classification) and radiologic (MR evidence of white-matter disease) criteria indicating late-stage HIV infection, reduced relative levels of NAA have been demonstrated. Spectroscopic abnormalities can be quantitatively tracked with time. This paper demonstrates the clinical use of detecting NAA as a putative in vivo measure of the neuronal loss that has been demonstrated in postmortem studies of patients with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated cognitive/motor complex, is thought to be attributable directly or indirectly to the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative noninvasive indicator of this aspect of cerebral involvement in HIV disease.     

False-Positive Computed Tomographic Findings in a Series of 525 Patients with Acoustic Neuromas

In our series of 525 patients operated on for acoustic neuroma, there were three false-positive computed tomography findings resulting in unnecessary surgery. The histories and results of laboratory investigations and surgery are presented. Discussion of the outcome had gadolinium-enhanced magnetic resonance imaging been performed is presented.