Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.

This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.

Loss of a chance in medical malpractice litigation: expanding liability of health professionals versus providing justice to those who have lost.

The loss of a chance doctrine in medical malpractice litigation is essentially based on the perceived unfairness of denying recovery to a patient when a health provider's malpractice has reduced the patient's chance of a better outcome. It is the thesis of the article that loss of a chance must the recognised at law, notwithstanding that the chance is less than even or not subject to the benefit of statistical and/or scientific proof and that each lost chance should be assessed according to the value of that chance. Varying approaches to allocating value to the chance lost are examined both historically and internationally. The author contends that the policy arguments--which include potential for increased medical malpractice litigation, tainted reputations and an increase in professional indemnity policies--are insignificant when compared to the value and quality of human life and therefore cannot be supported.

Setting occupational exposure limits for sensory irritants: the approach in the European Union.

Beginning in 1990, the European Commission initiated a program to establish European Union (EU)-wide occupational exposure limits (OELs). As in the United States and other countries, a panel of experts known as the Scientific Committee on Occupational Exposure Limits (SCOEL) was identified and brought together to identify the proper values. This article describes the approach used by SCOEL to identify appropriate values for sensory irritants. The EU panel believes that irritant effects in the eyes and respiratory tract can produce symptoms that range from trivial to serious, and that responses to irritants may be viewed as belonging to a continuum. One of the interesting differences between the approach used by the ACGIH TLV committee and the SCOEL is the use of five grades of irritation to evaluate this class of chemicals. For purposes of setting an OEL, the SCOEL makes no distinction between irritation or nuisance and related somatic effects such as headache. How the committee established an OEL for ethyl acetate is offered as an illustrative example.

Collagen vascular diseases: cutaneous manifestations in ophthalmology.

PURPOSE: To describe the effects of collagen vascular diseases on the eyelids and periorbital tissues. METHODS: Retrospective review of dermatologic pathology slides at Massachusetts General Hospital and eye pathology slides at Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. RESULTS: A spectrum of dermatologic manifestations of collagen vascular diseases was observed, affecting the eyelids and periorbital region. CONCLUSIONS: Collagen vascular diseases may present complicated diagnostic and clinical challenges for the practicing ophthalmologist. Familiarity with the cutaneous periocular manifestations of these diseases may facilitate early recognition, diagnosis, and ophthalmologic intervention where necessary.

A brief history of the randomized controlled trial. From oranges and lemons to the gold standard.

This article discusses the history and development of randomized clinical trial methodology, the reasons for its status and authority as a method of therapeutic evaluation, and the continuing role of clinical judgement in designing, interpreting, and applying the findings of trials.

Toward a canon of the pain and analgesia literature: a citation analysis.

UNLABELLED: The purpose of this study was to use citation analysis to identify major themes and contributors to the pain and analgesia literature over the past two decades. A citation analysis was performed on a database of more than 110,000 articles in the biomedical literature from January 1981 through June 1997, and in the interval from January 1988 through June 1997. Articles and authors related to pain and analgesia research and practice were identified by searching approximately 7,700 journals. The 20 articles and 20 authors with the most citations were then checked by hand to ensure relevance to pain or analgesia. Most of the high-impact articles identified pertained to research on basic pain pathways. Nearly all the articles concerned opioids, nonsteroidal antiinflammatory drugs, and consequences of analgesic use. None of the highest-impact articles address assessment of clinical pain. Few women were first authors of any most frequently cited paper. Citation analysis is a useful tool in identifying important contributions to the biomedical literature. Recent and continuing research trends include the use of nonsteroidal antiinflammatory drugs, opioid mechanisms, and persistent pain disorders. Current trends expected to become stronger include description of pain from the patient's perspective and mechanisms of the transition from acute to chronic pain. IMPLICATIONS: We performed a citation analysis to identify important contributions and contributors to the biomedical literature. Recent pain and analgesia research has been focused on mechanisms of pain, but evidence suggests the importance of understanding the pain experience from the patient's perspective and the transition from acute to chronic pain.

Necrotizing fasciitis after cosmetic blepharoplasty.

PURPOSE: To report a case of necrotizing fasciitis after cosmetic blepharoplasty. METHOD: Case report. A 74-year-old woman with history of type II diabetes mellitus underwent bilateral upper eyelid blepharoplasty. Postoperatively she developed fever, grayish discoloration of the skin, violaceous bullae, and a right facial nerve palsy. Necrotizing fasciitis was diagnosed and treated with intravenous antibiotics, debridement of necrotic tissue, and hyperbaric oxygen therapy. RESULTS: The infection resolved, but the patient required reconstruction for correction of cicatricial ectropion. CONCLUSION: Necrotizing fasciitis is a potentially fatal infection that typically occurs in the setting of trauma. Early recognition of its pathognomonic signs and aggressive management are paramount.

Toxicology of hydrogen fluoride in relation to major accident hazards.

A major industrial accident involving the release of hydrogen fluoride has the potential to cause serious injury and possibly death in the surrounding human population. Given the potential for such serious and large-scale effects, there is a need for scientifically based risk assessments for determining appropriate on-site risk control measures, as well as for informing off-site emergency plans and land-use development decisions. Within Great Britain, the Health and Safety Executive (HSE) has the statutory responsibility for providing land-use planning advice in the vicinity of major accident hazard sites. The advice is based on quantified assessment of the individual risk of exposure to a specified amount of the toxic substance. Among other things this requires a consistent, reliable, and transparent understanding of the major hazard toxicology of the substance concerned. An assessment of the toxicology of hydrogen fluoride in relation to major accident hazards, based on conventional inhalation toxicity studies, was published by HSE in 1993. Recently, studies have been reported in which rats inhaled hydrogen fluoride via a mouthpiece attached to an endotracheal cannula. HSE has explored the use of this "mouth-breathing" rat model as a possible basis for human health risk assessment for hydrogen fluoride in the context of major accident hazards. A number of uncertainties in the use of this animal model have been identified that warrant caution in the use of this model for regulatory purposes. Overall, the results from the "mouth-breathing" rat model did not lead to a change in the HSE assessment of hydrogen fluoride, which remains based on experimental data obtained following "mainstream" toxicological practices.

Desmoplastic spindle-cell melanoma of the eyelid with orbital invasion.

PURPOSE: To describe the clinicopathologic features of a patient with a spindle-cell melanoma of the eyelid that exhibited orbital invasion. METHODS: Case report. RESULTS: A slowly enlarging mass developed in the eyelid of a 50-year-old woman. Excision of the mass showed desmoplastic spindle-cell melanoma. The tumor recurred in the orbit, and an exenteration was performed. A second recurrence 7 months later was treated with radiation therapy. CONCLUSIONS: There is a continuum of spindle-cell to desmoplastic melanoma. The prognosis of patients with orbital invasion of melanoma is poor, and adjuvant treatment including radiation and chemotherapy has little benefit.

Sino-orbital aspergillosis in acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical features, causes, imaging characteristics, treatment, and outcome of patients with the acquired immunodeficiency syndrome (AIDS) and sino-orbital aspergillosis. DESIGN: Records of 5 patients were reviewed. Results of imaging and histopathologic examinations and clinical courses of the patients were studied. RESULTS: There were 3 women and 2 men (mean age, 34.0 years). All had received a diagnosis of AIDS, and mean CD4+ cell count was 0.014 x 10(9)/L (14 cells/mm3). Computed tomographic scanning exhibited heterogeneous, enhancing sino-orbital soft tissue lesions with bony erosion, and magnetic resonance imaging disclosed soft tissue masses hypointense on T1- and T2-weighted images. The infection involved 1 or more paranasal sinuses, with extension into the right orbit in 3 patients and into the left orbit in 2. Patients were treated with aggressive surgical debridement and intravenous antifungal agents. In addition, local irrigation of amphotericin B was performed in 3 patients. Aspergillus fumigatus was found to be the cause in all 5 patients. Intracranial extension developed in 4 patients, and all subsequently died. The 2 longest surviving patients were the only ones being treated with protease inhibitors. Three patients had a history of frequent marijuana smoking. CONCLUSIONS: Sino-orbital aspergillosis is a progressive, relentless, and usually fatal opportunistic infection of advanced AIDS. Patients are first seen with long-standing headache and proptosis with minimal external inflammatory signs. Marijuana smoking may increase the risk for development of sino-orbital aspergillosis in these patients. Aggressive surgical and medical treatment, combined with newer combination therapies using protease inhibitors, may improve the longevity of these patients.

Neoadjuvant intracarotid chemotherapy for treatment of advanced adenocystic carcinoma of the lacrimal gland.

OBJECTIVE: To investigate a new chemotherapeutic regimen as an adjunct to the conventional surgical management of patients with advanced adenocystic carcinoma of the lacrimal gland. PATIENTS AND METHODS: Two patients with extensive adenocystic carcinoma of the lacrimal gland were treated with intracarotid cisplatin and intravenous doxorubicin hydrochloride prior to orbital exenteration. Postoperatively, the patients received 55 to 60 Gy of orbital irradiation, augmented by additional intravenous cisplatin and doxorubicin. Serial clinical and computed tomographic scan examinations were performed to monitor for evidence of recurrent disease. RESULTS: Tumor shrinkage was documented radiographically following this preoperative chemotherapy regimen, downstaging the disease in one case from intracranial involvement to a more surgically amenable intraorbital process. Tumor necrosis was confirmed in the exenteration specimen. Limited morbidity was experienced and both patients have achieved long-term survival to date of 9 1/2 years (114 months) and 7 1/2 years (94 months). CONCLUSIONS: To our knowledge, this is the first report of the efficacy of neoadjuvant intracarotid chemotherapy in the treatment of an advanced adenocystic carcinoma of the lacrimal gland. The combination of cisplatin and doxorubicin and the methods of drug delivery may be factors contributory to the favorable response. The results of this new treatment regimen are encouraging and justify further investigation.

Use of galeal or pericranial flaps for reconstruction or orbital and eyelid defects.

The use of galeal or pericranial flaps for craniofacial reconstruction is well recognized. The excellent blood supply of the flap permits vascularized support for skin, bone, or cartilage grafts in otherwise unsatisfactory recipient sites. The pericranial flap was used in 1 patient with a large orbital bony defect and the galeopericranial flap was used in 3 patients with various periocular defects produced by trauma or following tumor extirpation. In the case of an orbital defect induced by chronic cocaine abuse, the pericranial flap successfully sequestered the orbit from the nasal cavity while providing support for the globe. In 3 of the 4 cases involving eyelid reconstruction, the galeopericranial flap served a dual function in providing vascular supply to the underlying free tarsal graft and to the overlying free skin graft. This tissue flap is analogous to a median forehead flap, except skin is not transposed and a second-stage inset revision is not required.

Cataract extraction after silicone oil repair of retinal detachments due to necrotizing retinitis.

Cataract is common after silicone oil repair of retinal detachment due to necrotizing retinitis in acquired immunodeficiency syndrome. Surgical management has not been reported. Twenty-two eyes of 19 patients were reviewed. The majority underwent phacoemulsification with a posterior chamber convexoplano implant without iridotomy Complications included capsular fibrosis and hyphema. Unpredictable refractions in the first 16 eyes prompted refinement of lens calculations and resulted in a reduction in refractive errors. A 3-step modification of intraocular lens calculations is recommended: (1) use of specific sound velocities to calculate axial length; (2) use of convexoplano lenses; and (3) addition of a constant to the lens power to compensate for the refractive index of silicone oil. Good surgical technique and accurate lens calculations should improve management of cataracts that arise after retinal detachment repair with silicone oil in patients with acquired immunodeficiency syndrome.

"Simple methods" and "determined contraceptors": the statistical evaluation of fertility control, 1957-1968.

PIP: This paper discusses the use of two US research projects in legitimizing fertility control through the authority of scientific research. The projects included field trials of "simple methods of contraception" and IUDs that were sponsored by the US Population Council and the Planned Parenthood Federation of America (PPFA). Research was used to test whether simple methods and the IUD were safe and effective. In 1957, contraception research did not have the support of the academic medical leadership, and most state health departments did not distribute birth control literature. The clinical field trials were conducted through 95 PPFA-affiliated centers under the direction of PPFA's Medical Director Mary Calderone during 1957-64. The institutional affiliation served to give legitimacy to PPFA and to validate use-effectiveness of creams, jellies, or spermicides with a diaphragm. The Population Council reactivated the National Committee on Maternal Health (NCMH) with Christopher Tietze as head and as a member of the Advisory Committee of the new PPFA Clinical Investigation Program. Clarence Gamble, who believed in the "anything that works approach," severed his relationship with NCMH. Calderone thought that "any method was better than no method, but the most critical factor in effectiveness was availability." What was innovative about these trials was the study of the practice of contraception and the use of a statistical measure. The trials found that the diaphragm was the most effective and acceptable method. The EMKO brand was the most popular foam. Tietze's evaluation of five different IUDs during 1963-68 did not meet the rigorous criteria of Louis Lasagna, but did determine the regularity and continuity of contraceptive practice. Life table methods were used to demonstrate a statistically valid result. By 1964 contraception became recognized in the medical field. By 1968 a statistically valid result among "determined contraceptors" established the medical legitimacy of the IUD, and global distribution ensued.^ieng

Glutamate efflux from rat brain slices and cultures: a comparison of the depolarizing agents potassium, 4-aminopyridine, and veratrine.

The major excitatory amino acid neurotransmitter in the mammalian brain is glutamate (GLU). GLU release from nerve terminals is both calcium-dependent and -independent, yet these mechanisms of release are not fully understood. Potassium, 4-aminopyridine (4-AP) and veratrine are commonly used depolarizing agents that were studied for their ability to stimulate GLU efflux from brain slices. These agents produced significant regional variations in GLU efflux from rat brain slices. Potassium was the most potent of the three secretogogues tested. 4-AP produced a significant GLU efflux only in the cerebellum. Veratrine produced consistent stimulation of GLU efflux from all brain regions tested. Potassium was the only depolarizing agent tested that stimulated GLU release from primary astroglial cultures of rat cerebral cortex. All three agents also demonstrated an ability to inhibit GLU reuptake in brain slice preparations. This data suggest that both GLU release and uptake are modulated in a regionally selective manner, and that commonly used depolarizing agents affect not only calcium-dependent neuronal release, but also uptake and glial responses.