Occupational transmission of HIV in health care workers: A review

Health care workers have a small but real risk of acquiringHIV infection as a result of occupational exposure. In thispaper, we review all reports in the scientific literature from1984 through to December 1993 of confirmed and probable casesof HIV seroconversion after a specific occupational exposure.A total of 64 confirmed cases have been reported, 24 in Europe,36 in the USA and 4 in other countries. Most seroconversionshave resulted from percutaneous exposure (91%) to AIDS patients(62%), usually caused by hollow bore needlestick injuries inflictedduring blood drawing procedures. Almost all seroconversionshave been detected within 6 months of exposure (94%) and haveusually been preceded by an episode of acute illness (73%).Ten seroconversions have occurred in spite of partial or completecourses of zidovudine prophylaxis. An additional 113 probablecases have been reported, 75 in the USA, 35 in Europe and 3in other countries. Aggregating the results of the prospectivestudies carried out, it is calculated that the risk of seroconversionfollowing percutaneous exposure is 0.33% or 3 in 1000 exposures(95% Cl: 0.21–0.52%), while the risk following mucocutaneousexposure is much lower (0.04%, 95% Cl: 0.006–0.31%). Thedocumented failure of zidovudine prophylaxis following occupationalexposure in a number of instances indicate its effect is, atbest, only partial; furthermore, exposure to source patientswho have been receiving the drug may lead to transmission ofzidovudine-resistant strains of HIV. Risk factors for occupationalexposure to HIV and for transmission, given that an exposurehas occurred, are discussed.     

Potentiation of the mitogenic effect of estrogen on the pituitary-gland by alcohol-consumption

The effect of alcohol on estrogen-regulated lactotropic cell proliferation was examined in Fisher 344 rats. Alcohol was administered for 2 weeks using liquid diet containing 8.7% ethanol (v/v) and 37% ethanol-derived calories. The control group was pair-fed with an isocaloric diet minus the ethanol or adlib-fed with normal diet. Ethanol-treated rats showed mean blood ethanol concentrations between 60-90 mg/dl. Alcohol treatment did not effect the body growth rate, but increased the DNA synthesis in lactotropes and reduced the levels of lactotropic growth inhibitory transforming growth factor-beta 1 (TGF-beta 1) protein and mRNA in the pituitary. These results suggest that alcohol promotes estrogen-induced lactotropic proliferation, possibly by down regulating the inhibitory TGF-beta 1 control of lactotropic function.     

The mechanism of directional coronary atherectomy

An attempt was made to assess the mechanism of directional coronaryatherectomy using different methods of analysis. Quantitativecoronary angiography was used as the gold standard to assessthe immediate results of atherectomy, and a comparative quantitativeanalysis of atherectomy and balloon angioplasty was made. Todetermine whether the post-atherectomy cross-sectional areais close to a circle, we compared the area measurements obtainedby edge detection with those obtained by videodensitometry.Finally, the extent of a ‘Dotter’ effect was establishedby quantitative angiography following crossing the stenosiswith the atherectomy device. For the purpose of this study,the results of the first 113 successful atherectomy procedureswere reviewed. In matched lesions, directional atherectomy induceda greater increase in minimal luminal diameter than balloonangioplasty (1.6 mm vs 0.8 mm; P < 0.0001 However, this luminalimprovement is due to a substantial ‘Dotter’ effectinduced by the bulky atherectomy device. Following atherectomy,only a slight difference in cross-sectional area measurementsbetween edge detection and videodensitometry (mean difference:0.28 mm² was found. Histologic examination of an atherectomizedcoronary artery showed a near-circular post atherectomy areageometry. In conclusion, directional atherectomy is a very effectivedevice with a substantially better initial result than balloonangioplasty. However, insertion of this bulky device itselfcauses an important ‘Dotter’effect.     

CALCITONIN GENE-RELATED PEPTIDE II, SUBSTANCE P AND VASOACTIVE INTESTINAL PEPTIDE IN PLASMA AND SYNOVIAL FLUID FROM PATIENTS WITH INFLAMMATORY JOINT DISEASE

Immunoreactive plasma and synovial fluid concentrations of calcitoningene-related peptide II (CGRP II), substance P and vasoactiveintestinal peptide (VIP) were measured in patients with osteoarthritis,gout and rheumatoid arthritis. Significantly higher levels ofCGRP II and substance P and VIP-like immunoreactivity levelsin synovial fluid were found in gout as well as CGRP II, substanceP and VIP-like immunoreactivities in rheumatoid arthritis whencompared to those in osteoarthritis. Plasma CGRP II, substanceP and VIP-like immunoreactivity levels showed no significantdifferences among patients in the three different groups ofarthritis. Our results suggest that these neuropeptides releasedfrom peripheral nerve endings into the synovial cavity probablyplay a pathogenic role in human joint inflammation. KEY WORDS: Rheumatoid arthritis, Gout, Calcitonin gene-related peptide II, Substance P, Vasoactive intestinal peptide, Synovial fluid     

VOLTAGE FIELDS SURROUNDING NEEDLES USED IN REGIONAL ANAESTHESIA

Using a bench model, we have studied the voltage fields surroundingboth insulated and uninsulated needles used in regional anaesthesia.The findings were compared with earlier computer predictionswhich suggested that the fields would be markedly differentfor the two types of needle. The results confirm that the fieldsdiffer markedly and suggest that the use of insulated needlesmay not necessarily improve the accuracy of nerve location andthat uninsulated needles may be more appropriate. ^*Present addresses: Department of Anaesthetics, Hull Royal Infirmary,Hull, Humberside. Droitwich Knee Foundation, Saga House, SansomePlace, Worcester Present addresses: Droitwich Knee Foundation, Saga House, SansomePlace, Worcester.     

FUNCTIONAL ROLE OF CARDIAC PRESYNAPTIC α2-ADRENORECEPTORS IN THE BRADYCARDIA OF α-ADRENORECEPTOR AGONISTS IN PENTOBARBITONE- AND URETHANE-ANAESTHETIZED NORMOTENSIVE RATS

• 1 The relative potencies of 6 α-adrenoreceptor agonists, with differing physicochemical properties, at cardiac presynaptic α-adrenoreceptors were determined by measuring their ability to reduce the tachycardia produced by stimulation of the cardiac sympathetic nerves in pithed rats. The compounds studied were clonidine, B-HT 933 (azepexole), oxymetazoline, St 91, naphazoline and DPI.
• 2 The bradycardia produced by the same compounds in bilaterally vagotomized, urethane- or pento-barbitone-anaesthetized normotensive rats were also compared. The relative order of presynaptic potency appeared similar to that observed for the bradycardic activity of the compounds in urethane- and pento-barbitone-anaesthetized rats. In pentobarbitone-anaesthetized rats all compounds evoked a maximal effect of 18–20% reduction in heart rate. In urethane-anaesthetized rats, however, a difference was observed between clonidine and azepexole on the one hand and oxymetazoline, St 91, naphazoline and DPI on the other hand. The former induced a 20–22% reduction in cardiac frequency, whereas the latter diminished heart rate by 10–16% only. In vagotomized, bilaterally adrenalectomized, urethane-anaesthetized rats, clonidine, St 91, naphazoline and azepexole evoked a 25% reduction in heart rate, whereas a 20% reduction was observed for DPI and oxymetazoline.
• 3 A radio-enzymatic determination of plasma catecholamines demonstrated that under urethane-anaesthesia plasma adrenaline concentrations were significantly elevated over the values observed in pentobarbitone-anaesthetized rats. This rise in plasma adrenaline was related to the amount of urethane used. In urethane-anaesthetized, bilaterally adrenalectomized rats, plasma adrenaline was not significantly elevated.
• 4 These findings demonstrate the involvement of cardiac presynaptic α₂-adrenoreceptors in the acute bradycardia, evoked by the α-adrenoreceptor agonist upon intravenous application to pentobarbitone-anaesthetized, normotensive rats. In urethane-anaesthetized rats, however, the functional role of the cardiac presynaptic α₂-adrenoreceptors may be obscured as a result of the high plasma adrenaline levels observed in these animals.

     

IMPAIRMENT BY NIFEDIPINE OF VASOPRESSOR RESPONSES TO STIMULATION OF POSTSYNAPTIC α2-ADRENORECEPTORS IN GANGLION-BLOCKED RABBITS. FURTHER EVIDENCE FOR THE SELECTIVE INHIBITION OF POSTSYNAPTIC α2-ADRENORECEPTOR-INDUCED PRESSOR RESPONSES BY CALCIUM ANTAGONISTS

• 1 After ganglionic blockade and bilateral vagotomy, vasopressor responses induced by activation of postsynaptic α₁- and α₂-adrenoreceptors were elicited in the intact circulatory system of rabbits.
• 2 The hypertensive effects of the selective stimulating agents methoxamine (α₁-agonist) and B-HT 920 (α₂-agonist) were effectively antagonized by the adrenoreceptor antagonists prazosin and yohimbine, respectively. These findings confirm the existence of two types of postsynaptic α-adrenoreceptors (α₁-and α₂-type) in vascular smooth muscle of rabbits.
• 3 The calcium antagonistic drug nifedipine did not affect the maximal increase in diastolic pressure brought about by methoxamine, whereas it strongly inhibited the hypertensive effects of B-HT 920.
• 4 It is concluded that this confirmation of the selective inhibition of postjunctional α₂-adrenoreceptor-mediated vasopressor responses by a calcium antagonistic drug, such as nifedipine, indicates that this activity constitutes a general phenomenon. This finding supports the hypothesis that an influx of extracellular calcium is necessary for the vasoconstriction mediated by postsynaptic α₂-adrenoreceptors.

     

Neoadjuvant cisplatin plus ifosfamide in patients with stage IIB cervical cancer: a single center phase II study

The objective of this study was to evaluate cisplatin plus ifosfamide as neoadjuvant chemotherapy with regard to toxicity and clinical response in patients with stage IIB cervical cancer. Sixty-eight patients with previously untreated stage IIB cervical cancer were given two cycles of chemotherapy: cisplatin 20 mg m⁻² on Days 1–5, infused over 1 h; ifosfamide 1.2 g m⁻² on Days 1–5 infused over 30 min. Mesna 120 mg m⁻² was administered as a bolus 15 min before ifosfamide, and a continuous infusion, delivering Mesna 1.2 g m⁻², was given subsequently over the next 16 hours. The treatment cycle was repeated on day 21. Responders were then randomized to surgery or radiation therapy. All 68 patients were evaluable for toxicity. Toxicity was found to be acceptable. One patient died at home one month after completion of the second treatment cycle. There was one grade 4 thrombocytopenia. Grade 3 toxicities included anemia in four patients, leucopenia and nausea and vomiting in one patient each. Sixty-two patients were evaluable for response. A clinical response was documented in 44 of the 55 evaluable patients (80%), with 17 complete responses (31%) and 27 partial responses (49%) (95% confidence limits 69%–91%, 19%–43%, and 36%–62% respectively). The intent-to-treat response rate was 64.7%. Twenty-one patients were randomized to surgery and 23 patients to radiation therapy. Amongst the eight patients with a complete clinical response, one patient had a complete pathological response and one patient had residual intra-epithelial neoplasia. The drug combination of cisplatin plus ifosfamide had acceptable toxicity and gave a clinical response rate of 80% in previously untreated patients with stage IIB cervical cancer.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.