The use of acyclovir in suspected encephalitis.

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.     

Characterization of ACTH mediated suppression of MHC class II expression by murine peritoneal macrophages.

The effect of ACTH on the expression of major histocompatibility complex (MHC) class II (I-A) glycoprotein by murine peritoneal macrophages was evaluated. ACTH suppressed the expression of I-A by macrophages in a time- and dose-dependent manner. ACTH mediated its effect by decreasing the level of I-A mRNA. ACTH suppressed the expression of I-A by macrophages from mice that are susceptible to the in vivo growth of mycobacteria but did not affect the expression of I-A by macrophages from Mycobacterium bovis strain (BCG)-resistant mice. The concentrations of ACTH required to suppress I-A expression were greater than that required for an effect on adrenal steroid production and may be related to the localized production of ACTH by lymphocytes and macrophages.     

Cerebral accumulation of Tc-99m ethyl cysteinate dimer (ECD) in severe, transient hypothyroidism.

Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying 'noneuthyroid' individuals.     

Restriction enzyme fingerprinting of enterobacterial plasmids: a simple strategy with wide application

Restriction enzyme fingerprints were generated from purified plasmid DNA from 324 clinical isolates that belonged to 7 enterobacterial genera and 88 single plasmids in Escherichia coli K 12 according to the following strategy. Purified plasmid DNA was digested with PstI. The number of fragments detected in a 0.8 agarose gel was used to determine which 2 of 6 restriction enzymes including PstI was most likely to provide a fingerprint comprising sufficient fragments to ensure specificity but sufficiently few to allow easy visual assessment and minimize coincidental matching. When PstI produced greater than 20 fragments, EcoRI and HindIII were used; when PstI generated less than 6 fragments Bsp 1286 and AvaII were used and SmaI was employed when between 6 and 20 fragments were obtained from PstI digests. Using a minimum of 12 fragments from a combination of 2 enzymes as the criterion for characterizing a strain/plasmid, satisfactory 2-enzyme fingerprints were obtained from 87% of the strains and plasmids studied using PstI and no more than two additional enzymes per strain. Of the remaining 54 strains, 51 harboured only small plasmids (less than 10 kb) and 3 produced satisfactory fingerprints when digested with a fourth enzyme.     

An assessment of intrarenal hydrostatic pressure measurements in the diagnosis of acute renal allograft rejection

Postoperative intrarenal pressure measurements may be an aid to the diagnosis of acute renal transplant rejection, especially in patients treated with cyclosporine. Serial measurements of intrarenal pressure were made in 38 recipients using a fine-needle technique. Thirty-two intraoperative and 207 postoperative measurements were made, and 39 clinical rejection episodes (23 confirmed by biopsy) monitored. Intraoperative pressures in grafts with immediate function (37.4 +/- 4.0 mmHg, mean +/- SEM) were not significantly different from those with delayed function (30.9 +/- 4.8 mmHg), whereas postoperative pressures were greater (P less than 0.01) in kidneys with acute tubular necrosis (29.4 +/- 1.9 mmHg) than in functioning grafts (20.4 +/- 0.9 mmHg). Pressures recorded during clinical rejection episodes (44.3 +/- 2.3 mmHg) exceeded (P less than 0.001) those during quiescent periods (23.6 +/- 1.0 mmHg). During rejection episodes, higher pressures (P less than 0.01) were recorded from tender or palpably enlarged grafts (52.5 +/- 3.0 mmHg) than in the absence of these signs (36.3 +/- 3.1 mmHg), and patients whose transplants biopsies showed cellular rejection tended to have greater pressures (50.1 +/- 4.1 mmHg) than those with concomitant vasculopathy (36.4 +/- 3.9 mmHg), but the latter did not reach statistical significance. In 7 cases of cyclosporine toxicity the intrarenal pressure was 17.8 +/- 4.2 mmHg. Using a diagnostic cut off point of 40 mmHg, the investigation failed to recognize 26% of acute rejection episodes--and, in the presence of acute tubular necrosis, it wrongly categorized 21% of nonrejectors. While its predictive capacity was limited, the test may occasionally be helpful in the differentiation of cyclosporine toxicity and rejection in functioning kidneys.     

Coronary blood flow and cardiac adenine nucleotides in E. coli endotoxemia in dogs: effects of oxygen radical scavengers

The purposes of this study were to determine the effects of E. coli endotoxin shock on coronary blood flow (CBF) and myocardial adenine nucleotides and to determine if reactive oxygen species are major causal factors in these effects of endotoxin. Twenty-three pentobarbital-anesthetized Beagle dogs were instrumented for recording cardiorespiratory parameters, injected i.v. with saline (time-matched controls; n = 6) or endotoxin (1.5 mg/kg; n = 17), and studied for 4 h. Endotoxin dogs also received either i.v. saline (shock controls; n = 6) or i.v. treatment with either deferoxamine (30 mg/kg; n = 5) or triple therapy (n = 6) with a combination of allopurinol (150 mg/kg), superoxide dismutase (SOD) (5 mg/kg), and catalase (CAT) (5 mg/kg). Cardiorespiratory and tissue blood flow variables were constant in sham-shock controls during the study, whereas endotoxin dogs developed typical canine endotoxemia with decreased left ventricular (LV) function. CBF was decreased by approximately 40% (P less than or equal to 0.5) in all endotoxin groups throughout the 4 h study period. However, based on hemodynamic estimates of myocardial O2 demand and endocardial/epicardial blood flow ratios, it seemed that coronary flow was matched to metabolic rate in all endotoxin groups. Endotoxin significantly lowered LV myocardial concentrations of ADP, AMP, NADH, and NADPH (range = 37 to 54%, P less than or equal to 0.05), but ATP, NAD, and NADP concentrations were not changed. The adenylate charge of the myocardium was between 0.91 and 0.95 in all endotoxin groups, suggesting that adequate energy was available in the myocardium during endotoxin shock. The lack of influence of deferoxamine, allopurinol, SOD, and CAT is indirect evidence that oxygen radicals are not primary pathophysiologic mediators in the cardiac response to gram-negative endotoxemia in this endotoxin model.     

Impact of the revision of DUI legislation in Alabama

On May 19, 1980, a major revision in the Alabama DUI laws went into effect which gave judges greater discretion in sentencing. This revision resulted in an increase in the proportion of DUI convictions, a reduction in the number of DUI citations reduced to reckless driving, a reduction in the proportion of offenders acquitted and/or dismissed, an increase in the proportion of revocations, and an increase in court referrals to an educational program on the first offense. However, the 1980 revision was accompanied by a significant increase in the percentage of alcohol-related accidents. Consequently, the Alabama legislature revised the 1980 law on July 29, 1983, the revision taking effect immediately. The more stringent penalties in the new law apparently had a positive effect on all six alcohol-related measures cited above. Most importantly, the latest revision was accompanied by a significant decrease (2.80%) in the proportion of alcohol-related accidents.     

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate

Epidemiological studies have indirectly linked compounds ofchromium, nickel and arsenic to human carcinogenesis. However,there is no evidence that metal compounds can transform humancells to the tumorigenic phenotype in culture. We show herethat exposure to 36 µM NiS0₄ for 48–96 h resultsin transformation of an immortal, non-tumorigenic, osteoblast-likecell line, HOS TE85, to the tumorigenic phenotype. Continuouspassaging following treatment leads to the formation of a fewdense foci. The cells isolated and expanded from the foci aremorphologically transformed, and form anchorage-independentcolonies of the size and abundance comparable to that formedby Kirsten murine sarcoma virus transformed HOS TE85 cells.The transformed cells from tumors in nude mice, have enhancedlevels of plasminogen activators and have lost the ability toform model bone matrix on extended culture in the presence ofascorbic acid and ß-glycerophosphate. A number ofcell lines have been established from nude mouse tumors. Cytogeneticanalysis reveals 16 marker chromosomes and an aberrant chromosome16. This is the first report of the transformation of a humancell line to tumorigenic phenotype by a metal carcinogen.