How likely is it that Stockholm stage 1 of the hand arm vibration syndrome will progress to stages 2 and 3?

The progression of symptoms in the hand arm vibration syndrome (HAVS) is dependent on the interaction of individual and workplace factors. Workplace factors include type, magnitude and intermittency of exposure to hand transmitted vibration (HTV), anti-vibration tool design and workpiece characteristics. Individual susceptibility and constitutional factors are poorly understood and the reliance on anamnesis for diagnosis can lead to recall bias, inaccurate classification and an unreliable assessment of the stage of deterioration. This may be overcome by the adoption of multiple standardized testing. The introduction of a policy covering identification, risk assessment, health surveillance and reasonably practicable control measures will have the most significant impact on the incidence of new cases and deterioration in established cases.     

Flumazenil-precipitated panic and dysphoria in patients dependent on benzodiazepines: a possible aid to abstinence

Ten long-term users of benzodiazepines (average daily dose, 20 mg of diazepam or equivalent) who had experienced problems in withdrawing from the drugs were given an i.v. challenge with either the benzodiazepine antagonist flumazenil (1 mg injected over 30 s) or placebo (vehicle solution) in a randomized double-blind design. There were no 'pseudo withdrawal' responses to either single-blind or double-blind placebo injections, whereas flumazenil produced dramatic panic reactions in all four subjects tested, followed by characteristic benzodiazepine withdrawal symptoms. There were also small but significant rises in pulse rate and blood pressure, but no change in serum cortisol. Flumazenil-induced panic could not be entirely accounted for by a past or present diagnosis of panic disorder, and did not seem to be related to previous withdrawal problems, present benzodiazepine dosage, or to the severity of withdrawal symptoms precipitated by flumazenil in the same challenge test. Attempts to reduce benzodiazepine intake over the next 3 weeks tended to be more successful in the flumazenil group. The results are discussed with reference to possible changes in the GABA-benzodiazepine system in long-term benzodiazepine users.     

Comparative pharmacokinetics of propofol in Chinese adults and children.

The pharmacokinetics of propofol were studied in 14 healthy young male Chinese adults, aged 18-38 years, undergoing minor orthopedic surgery. All patients who received a single bolus dose of propofol 2.5 mg/kg were paralyzed with atracurium and mechanically ventilated. Anesthesia was maintained with 67% nitrous oxide plus 1-2% isoflurane in oxygen with alfentanil 5 micrograms/kg intravenously as a bolus injection. Blood concentrations of propofol over the subsequent 24 hours were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistently described by a three compartment model but analysis revealed two significantly different blood propofol concentration-time profiles (p less than 0.05). Five patients, designated "fast" metabolizers, demonstrated a mean elimination half-life which was shorter than that described in Chinese children, while their total body clearance was similar. Nine other patients, designated "slow" metabolizers, had a longer mean elimination half-life and slower total body clearance than those in elderly Caucasian patients. This may be suggestive of propofol metabolism at some extra-hepatic site in some patients, while other patients demonstrate marked lipophilicitic constraint of the drug by the deep compartment.     

Prodigious alcohol consumption by Australian rugby league footballers

As an incidental finding in a general 'life-style' survey, amateur rugby footballers were found to drink prodigious (12-24 schooners per session) quantities of beer. Such drinking was regarded by the players as part of the traditions of mateship associated with the game. The need for intervention is discussed.     

The combined sensate radical forearm and iliac crest free flaps for reconstruction of significant glossectomy-mandibulectomy defects.

The loss of motor and sensory function of the tongue following ablative surgery has a devastating effect on oral function. At the present time, there is no way to restore lost tongue musculature following partial glossectomy. The use of sensate cutaneous flaps has been shown to restore sensory feedback to reconstructed areas of the oral cavity. No single composite flap supplies a sensate soft-tissue component together with an osseous component of sufficient bone stock for functional mastication. In this article, the combination of the radial forearm free flap with the iliac crest osteocutaneous or osteomyocutaneous free flap is reported. The radial forearm free flap was used to resurface the resected portion of the tongue to provide maximum mobility and sensation. The lingual nerve was the recipient nerve for anastomosis to the antebrachial cutaneous nerves in all but one case. The iliac bone was used to reconstruct the mandible, with the iliac skin paddle or the internal oblique muscle used to reconstruct the neoridge. This combination of flaps was used in 10 patients. There was one flap failure due to vascular kinking from "piggybacking" the iliac crest to the distal end of the radial forearm flap. As a result, the use of two separate sets of recipient vessels is now advocated. Although a single composite free flap offers an excellent form of oromandibular reconstruction in most cases, it has been shown that oral function deteriorates when large areas of anesthesia are present in the oral cavity. We believe that this combination of two free flaps offers an opportunity for superior function in select patients with significant glossectomy and/or large mucosal defects.     

Reports by anaesthetists to procurators-fiscal: analysis of "anaesthetic deaths" over 10 years in four Scottish teaching hospitals.

Review of 489 "anaesthetic deaths" reported to procurators-fiscal over 10 years disclosed only 30 that were thought to justify such reporting. Most of the remainder occurred in patients so desperately ill at the time of operation that death was expected. Postmortem examinations ordered by the Crown authorities in nearly all cases were probably largely unrewarding and mostly unnecessary. The results suggest that the present regulation on reporting should be revised to focus more attention on the few deaths that occur in patients who have no apparent contraindication to anaesthesia or operation.     

Cure rates of oral contraceptive users and non-users when treated for vulvovaginal candidiasis (moniliasis) with miconazole nitrate 2% vaginal cream

Analysis of the data from a carefully conducted multi-investigator study utilizing 261 subjects with a diagnosis of vulvovaginal candidiasis determined the cure rates in oral contraceptive users as compared to the cure rates in oral contraceptive non-users when treated with miconazole nitrate 2% Vaginal Cream (MONISTAT¹). The criteria for a cure required that subjects have a negative KOH smear, negative NICKERSON'S Medium culture for $\text{Candida}$ species, and complete absence of the signs and symptoms of vulvovaginal candidiasis 30 or more days following the course of therapy. There was no significant difference in the cure rates of the oral contraceptive users when compared to the oral contraceptive non-users. It is concluded that there is no justification for routinely discontinuing oral contraceptive therapy during treatment for vulvovaginal candidiasis with miconazole nitrate 2% Vaginal Cream (MONISTAT).     

Preliminary assessment of the acute toxicity of malathion in animals

Laboratory studies were conducted to acquire information concerning the acute toxicity of malathion in animals under various conditions of exposure. The responses in rabbits and quail exposed to aerosols generated from technical grade malathion (95%) and approximating an ultra-low volume ground spray were compared with those from a 6% malathion/No. 2 fuel oil mixture simulating a high volume spray. Results indicate that technical grade malathion (95%) as an ultra-low volume spray and at effective insecticidal concentrations in particle sizes having a mass median diameter of about 12 µ is relatively nonhazardous compared to the possible toxic fuel oil effects of a 6% malathion/No. 2 fuel oil mixture with a mass median diameter of 25 µ. Based on blood plasma cholinesterase activity analyses, quail were more sensitive to equivalent malathion exposure concentrations than were rabbits. Oral administration of technical grade malathion to rabbits resulted in reduction of plasma and erythrocyte cholinesterase activity at dosages of 120, 300, and 600 mg/kg with death resulting from 1200 mg/kg.The opinions contained herein are those of the authors and should not be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Mention of proprietary products is for the purpose of identification only and does not imply endorsement by the Department of the Army.The experiments reported herein were conducted according to the Guide for the Care and Use of Laboratory Animals (1972) as prepared by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care, of the Institute of Laboratory Animal Resources, National Research Council.     

Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA.

A vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with alpha-TEA exhibiting greater proapoptotic effects. Although both VES and alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only alpha-TEA is an effective inducer of apoptosis. VES or alpha-TEA treatment of cp70 cells with 5, 10, or 20 microg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by alpha-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of alpha-TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-alpha-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show alpha-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-alpha-tocopherol, an ineffective apoptotic-inducing agent.     

Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.

PURPOSE: There is considerable evidence that the presence of mouse mammary tumor virus (MMTV)-like gene sequences in human breast cancer is highly associated with human breast carcinoma. Previous studies have found MMTV-like gene sequences in 38% of breast cancer tissue from United States women. The prevalence of these sequences in Australian and Vietnamese women has never been reported. EXPERIMENTAL DESIGN: Using PCR and primers that amplify MMTV-like gene sequences, we tested cancerous and benign breast tissue from Caucasian-Australian, Vietnamese-Australian, and Vietnamese women. RESULTS: MMTV-like gene sequences were amplified in 19 of 45 (42.2%) archival breast cancer biopsy tissues from Caucasian-Australian women, but only 1 of 120 (0.8%) and 0 of 41 breast cancer biopsy tissues from Vietnamese and Vietnamese-Australian women, respectively. The same sequences were found in only 2 of 111 (1.8%) and 0 of 60 normal (benign) breast tissue samples from Australian and Vietnamese women, respectively. CONCLUSIONS: MMTV-like gene sequences are found in only some human populations and are rarely found in normal human breast tissue from all populations, suggesting they are not present in the normal human genome and have been acquired.