The Department of Defense's Persian Gulf War registry year 2000: an examination of veterans' health status.

This study examined the health status of 46,633 Persian Gulf War theater veterans who received full clinical evaluations in the Department of Defense's Gulf War Comprehensive Clinical Evaluation Program (CCEP) as of spring 2000. Clinical data analyzed included demographic information, 15 health symptoms, 19 wartime exposures, and primary and secondary physician-determined medical diagnoses based on International Classification of Diseases, 9th Revision, Clinical Modification, criteria. Findings and discussions are arrayed, by gender, with comparative 1996 data from the Department of Veterans Affairs Health Examination Registry Program. Many veterans reported fewer physical symptoms now than during the time of the Gulf War. Many endorsed symptoms of joint pain, fatigue, weight change, and sleep disturbances. Most reported exposure to diesel fuel and the nerve agent antidote pyridostigmine bromide; far fewer female veterans reported combat involvement. The most frequent primary or secondary diagnosed medical conditions were musculoskeletal/connective tissue diseases, ill-defined conditions, and mental disorders. Female veterans were diagnosed more frequently with mental disorders. Symptom endorsement and diagnosis rates between the CCEP and the Department of Veterans Affairs registry were not dissimilar. Overall, the self-reported general health of veterans with symptoms was much poorer (females had higher rates of "fair to poor" health than males) than that of veterans with no reported symptoms.

IARC Monographs, volume 9: some Aziridines, N-, S-, & O-Mustards and Selenium - summary of data reported and evaluation.

It presents data reported and results of carcinogenicity evaluation for humans and animals of some chemical compounds.

Chronic hyperpigmentation from a heated mustard compress burn: a case report.

This is a case study of a woman who sustained a second-degree, partial-thickness burn of the midchest and medial breast distribution after the application of a heated mustard compress as a naturopathic remedy for a recent bout of pneumonia. This case study demonstrates the potential for hyperpigmentation and hypertrophic scarring associated with heated mustard burns. A photograph of the presenting burn with the region of hyperpigmentation 3 days after the injury is provided.

[Cutaneous burns caused by Yperite. Apropos of 2 new cases]. / Brûlures cutanées à l'Ypérite. A propos de deux nouveaux cas.

Based on two of their own cases, the authors review the lesions produced by Yperite. This chemical agent produces cutaneous burns which are quite characteristic; histological study of biopsies carried out on cutaneous lesions was used to define the effects on the epidermis and dermis. The treatment of patients, with this rare condition, remains symptomatic.

[The effect of psoriazin preparation on the morphologic and the histochemical liver image]. / Der Einfluss des Präparats Psoriazin auf das morphologische und das histochemische Leberbild.

The effect of Psoriazin-ointment, applied locally to the skin, has been examined by histochemical reactions and morphological examination in the rat's liver. It was found out that the longer application of the ointment changed the activity of all examined enzymes and the PAS reaction and caused a local steatosis of the hepatocytes.

[A case of generalized pustular psoriasis arising following the use of psoriazin]. / Sluchai generalizovannogo pustuleznogo psoriaza, razvivshegosia posle primeneniia psoriazina.

A case with a most severe course of psoriasis is described, developing after prolonged psoriazin therapy. The female patient has developed a condition threatening for life.

Chemical warfare. Cutaneous lesions from mustard gas.

Cutaneous lesions of eight patients evacuated from the Iran-Iraq war zone are reported. The patients were exposed to mustard gas, and there was a spectrum of dermatologic lesions. In the mild cases only there was a sunburnlike erythema, but in the most severe cases this erythema was followed by large and disseminated bullae, which histologically showed a subepidermal location with full-thickness epidermal necrosis. The resorption of these blisters was followed by hyperpigmentation, which was more evident in the intertriginous areas. In these last cases there also were ocular, respiratory, and gastrointestinal manifestations. In the skin this mustard gas seems to act through a primary irritant mechanism and without allergic contact sensitization.

An altered lectin binding to mucus glycoprotein in goblet cells of human tracheobronchial epithelium among former mustard-gas workers.

Lectins, which are well known to have an ability to bind with specific carbohydrate residues of glycoprotein, have been used to examine cellular changes associated with malignant transformation. For the analysis of mucus glycoprotein of goblet cells in the tracheobronchial epithelium, 192 paraffin-embedded sections from 54 autopsy cases including the cases with a history of mustard-gas (MG) exposure were stained with seven plant lectins using PAP method. PNA binding with no neuraminidase treatment as well as BSA-1 binding was observed most frequently in MG-exposed lung cancer cases. The proportion of cases positive for SBA binding in MG-exposed and/or lung cancer cases had a statistical difference from non-MG-exposed non-lung cancer cases. These observations may indicate a large heterogeneity in oligosaccharide chains of mucus glycoprotein and suggest its incomplete or abnormal synthesis, which is most likely to be due to previous exposure to carcinogen, such as MG.

Early cancer and related lesions in the bronchial epithelium in former workers of mustard gas factory.

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.

[Late manifestations in former mustard gas workers with special reference to cutaneous findings]. / Spätmanifestationen bei ehemaligen Kampfgasarbeitern unter besonderer Berücksichtigung der cutanen Befunde.

We report on late cutaneous manifestations following exposition to gas (in particular N- and S-LOST) which had not been observed until within the last years. In the years 1945 to 1951, inadequate protective measures during disbandment of the "Heeresmunitionsanstalt St. Georgen" caused contamination and inhalation of these radiomimetics in about 400 persons. Apart from the still today little known pulmonal and cardiac late manifestations, the surviving persons now suffer from multiple skin tumors, such as basal cell carcinomas, Bowen's disease, Bowen's carcinoma and carcinoma spinocellulare even in unexposed parts of the skin. Moreover, there are observed spontaneous flat and partly necrotic, gangrenously imposing, very painful ulcerations with tendency to spread, which keep unaffected by all therapeutic measures. The findings have been documented historically, macroscopically, histologically as well as cytologically. Presentation of these late sequele is of particular importance since at that time containers with mustard gas had been unloaded anywhere in the FRG without any special precautions, so that also contamination of citizens has to be assumed. For this reason, similar findings are to be expected throughout the country, accumulated in certain regions. This additional aspect has also to be considered concerning the application of these radiomimetics therapy of psoriasis ("Russian ointment").

Phase II trail of PCNU in refractory advanced breast cancer.

An evaluation of PCNU was carried out in 28 patients with extensively treated refractory breast cancer. The starting dose was 60 mg/m2 in 13 patients and 90 mg/m2 in 15 patients given intravenously every 6 weeks. The major side effect was myelosuppression, manifested mainly as thrombocytopenia. Nonhematologic side effects were minimal, consisting mainly of transient nausea. One mixed response was seen. Four patients had stable disease. PCNU demonstrated limited activity in advanced breast cancer and was not effective in the treatment of central nervous system metastases.

Phase I trial and clinical pharmacology of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea.

1-(2-Chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (NSC 95466) is a lipid-soluble nitrosourea that is presently undergoing clinical evaluation. In this Phase I study, the toxicity of this drug was examined after administration of the drug to cancer patients on 3 successive days every 6 to 8 weeks. Clinical pharmacology was studied using 1-[chloroethyl-14C](2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea. The dose-limiting toxicity was myelosuppression. The maximal tolerated dose was 105 mg/sq m, which produced a median platelet nadir of 40,000/microliter on Day 32 and a median white blood cell count nadir of 2200/microliter on Day 42. Progressive anemia was also observed. There was no evidence of acute or chronic hepatic, renal, or pulmonary damage. One patient with a metastatic hypernephroma exhibited a partial clinical remission. Plasma disappearance of the drug following bolus administration was biphasic, with an initial half-life of 18 to 25 min and a second half-life of 9 hr. Clearance of intact drug coincided largely with the initial disappearance phase of total radioactivity. Entry of radioactivity into the cerebrospinal fluid was observed. Approximately 35% of plasma radioactivity was protein bound, the major binder being albumin. Drug excretion was predominantly renal, and biliary elimination was only minor.

Phase I trial of PCNU administered by 5-day courses.

PCNU was selected for clinical trials based on high activity in both standard and intracisternally transplanted murine tumors. PCNU was administered of five daily to 24 patients with refractory advanced solid tumors by courses of five daily iv injections every 6 weeks. The total dose ranged from 25 to 125 mg/m2/course. The major dose-limiting toxicity was reversible thrombocytopenia, with the nadi at 28-49 days and recovery by 2 weeks later. At a dose of 125 mg/m2/course, the mean nadir platelet count was 77 X 10(3)/mm3 (range, 16-201 X 10(3)/mm3). Recovery time was prolonged with successive courses in four patients, suggesting cumulative toxicity. The mean nadir of leukopenia at this dose was 2.6 X 10(3) cells/mm3 (range, 1.2-5.0 X 10(3) cells/mm3) and tended to occur with a later median at Day 44. Nausea and vomiting were unusually mild for a nitrosourea. Sporadic transaminasemia and elevated LDH may have been related to the vehicle, N,N'-dimethylacetamide. Other major organ toxic effects were not encountered, and there were no objective responses. PCNU was found to be a base-substitution mutagen in the Salmonella typhimurium assay. A starting dose of 125 mg/m2, divided into five daily doses, is suggested for phase II trails in patients with no significant hematologic compromise from prior chemotherapy or radiation, and a dose of 75 mg/m2 is recommended for all others.

Cancer of the larynx and other occupational hazards of mustard gas workers.

An attempt was made to tract 511 men and women who manufactured mustard gas during the 1939--1945 war. Despite limitations in the identifying data available, 428 (84%) were traced to the end of 1974. The numbers of deaths from all neoplasms combined (45) and from all other causes (136) were slightly greater than those expected from national death rates, but not significantly so. Two deaths were attributed to carcinoma of the larynx and one to carcinoma of the trachea, compared with an expected number of 0.40 (P less than 0.02). Carcinoma of the larynx was also mentioned on the death certificate of another man. Seven subjects are known to have developed cancer of the larynx, compared with 0.75 expected (P less than 0.001). Excess mortality was also observed from cancer of the lung, pneumonia and accidents, but the excesses were small and difficult to interpret.

Iatrogenic carcinogenesis.

In a wider sense iatrogenic carcinogenesis means the induction of cancer by medical treatment. Some drugs have been now identified to be carcinogenic not only in experimental animals but also in man. For example, chlornaphazine used in the treatment of polycythemia has been proved to induce bladder cancer in 30% of the patients treated. This is also true for alkylating agents which are used as cytostatics in cancer treatment. Adjuvant chemotherapy must be used with due caution. There is probably one iatrogenic carcinoma in 10,000 cases. Hence, it is important to analyze the risk-benefit ratio of such drugs.