Lymphadenopathy associated virus infection of a blood donor--recipient pair with acquired immunodeficiency syndrome.

A retrovirus isolated from three patients with the acquired immunodeficiency syndrome (AIDS) in the United States was morphologically and antigenically identical to lymphadenopathy associated virus isolated in France. Two of these isolates were from a blood donor-recipient pair, each of whom developed AIDS. Lymphadenopathy associated virus was isolated from the blood donor's lymphocytes 12 months after his onset of AIDS symptoms and from the blood recipient's lymphocytes 1 month after her onset of AIDS symptoms. Two isolates from the blood donor-recipient pair and an isolate from an epidemiologically unrelated homosexual man were examined by competitive radioimmunoassay to determine their antigenic relatedness to each other and to other human retroviruses. The major core proteins (p25) of the isolates were antigenically identical and all three isolates were identical to prototype lymphadenopathy associated virus isolated in France.

Lung cancer in Louisiana: death certificate analysis.

In a search for etiologic clues, a review was made of death certificates of residents in a cluster of Louisiana parishes, mainly in the southern part of the state, where lung cancer mortality was high. A comparison of the statements on occupation for 3,327 patients with lung cancer and those of 3,327 controls (matched by sex, race, age, and parish of residence) during 1960-75 revealed an approximately twofold excess risk associated with transportation equipment manufacture, mainly shipbuilding, and the fishing industry. Smaller elevations of lung cancer risk were found among older men who had been employed in petroleum exploration and production and among male and female residents of towns where the petroleum industry was a major employer. In addition, Acadian ancestry was associated with a higher risk of lung cancer among older male and female residents.

CNS toxoplasmosis in acquired immunodeficiency syndrome.

Several distinct patterns of neurological involvement occur in epidemic acquired immune deficiency syndrome (AIDS). Two patients with this disorder had Toxoplasma gondii encephalitis, one suspected and one proved. Computed tomographic (CT) scanning showed focal lesions in both patients. Spinal fluids were remarkable for elevated protein, hypoglycorrhachia, and absence of pleocytosis. In patients with AIDS, focal CT scan findings and serum indication of past T gondii infection should prompt strong consideration of the diagnosis of CNS toxoplasmosis. The absence of specific IgM antibody or rise in IgG antibody titer to T gondii does not exclude this condition in the immune compromised host. In the patient with AIDS, CNS lesions mimicking brain abscess warrant biopsy or empiric therapy for T gondii. Early recognition and initiation of a prolonged or indefinite course of pyrimethamine plus sulfonamide therapy could reduce the mortality associated with this infection in AIDS. Computed tomographic scans, repeated frequently, appear, at present, to be the best guide to monitor the status of CNS involvement.

Clinical drawbacks of total lymphoid irradiation: the cons.

Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.

Serial changes in markers of disease activity with corticosteroid treatment in sarcoidosis.

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced vital capacity, from 59.2 +/- 5.5 to 70.5 +/- 5.3 percent of the predicted value (p less than 0.001, Student paired t test), serum angiotensin-converting enzyme levels, from 66.0 +/- 12.1 to 28.2 +/- 4.0 U/ml (p = 0.003), 67gallium lung scanning scores, from 3.6 +/- 0.2 to 0.8 +/- 0.3 (p less than 0.001), serum gamma globulin levels, from 2.40 +/- 0.2 to 1.5 +/- 0.1 g/dl (p less than 0.001), and erythrocyte sedimentation rate, from 26.8 +/- 2.7 to 14.8 +/- 3.0 mm per hour (p less than 0.001). Changes in percent of bronchoalveolar lavage fluid lymphocytes were less impressive (from 28.7 +/- 4.9 to 21.2 +/- 5.1, p = 0.034), but the geometric mean number of bronchoalveolar lavage fluid-IgG-secreting cells decreased from 23,861 to 3,830 (p = 0.013). Serial evaluations in five patients treated with decreasing doses of alternate-day prednisone for an additional 10 1/2 months indicated that changes in 67gallium lung scanning scores corresponded most closely to the clinical course in five of five patients. Determination of serum angiotensin-converting enzyme levels also closely paralleled the clinical course in four of five patients, whereas the other parameters measured were more variable markers of clinical response. However, abnormalities of bronchoalveolar lavage fluid-IgG-secreting cells often persisted in the absence of clinically evident disease, and the percentages of bronchoalveolar lavage fluid lymphocytes were frequently normal in patients who responded subsequently to corticosteroids. Larger prospective studies are warranted to more extensively evaluate various measurements of disease activity, especially bronchoalveolar lavage fluid analysis, in sarcoidosis.

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

Response of AIDS-related thrombocytopenia to intravenous and oral azidothymidine (3'-azido-3'-deoxythymidine).

A patient with AIDS-related thrombocytopenia (ART) was treated with the new anti-retroviral agent azidothymidine (AZT, Retrovir, zidovudine) by the intravenous and oral routes for a period of 20 weeks. After a 6 week period of initial treatment, the platelet count rose from 38,000 to 140,000/mm3. AZT was intentionally discontinued for three weeks over which the platelet count declined to 70,000/mm3. After reinstitution of AZT, the platelet count rose once again and remained near normal levels for over one year. We conclude that AZT may have efficacy against the thrombocytopenia observed in some patients infected with human immunodeficiency virus (HIV). The pathogenesis of ART and the mechanisms of action of AZT in this condition remain unknown.

Case-control cancer mortality study and chlorination of drinking water in Louisiana.

Several Louisiana parishes (counties) using the Mississippi River for their source of public drinking water have the highest mortality rates (1950-69) in the United States for several cancers. Therefore, a case-control mortality study on cancer of the liver, brain, pancreas, bladder, kidney, prostate, rectum, colon, esophagus, stomach, non-Hodgkin's lymphoma, multiple myeloma, leukemia, Hodgkin's disease, lung; breast and malignant melanoma, from 1960 to 1975 in South Louisiana parishes grouped for similarities in industrial characteristics, having approximately equal exposure of the population to surface and groundwater, was conducted. Noncancer deaths were randomly selected as controls and matched to the case death on age, race, sex, and year and parish group of death. Water source at death was assigned based on the residence at death and described as surface or ground and chlorinated or nonchlorinated. A significantly increased risk for surface, chlorinated water use was noted for rectal cancer. No risk could be demonstrated for colon cancer. The risk noted for bladder cancer by other investigators is not substantiated. Brain cancer risk appears to be associated with chlorinated groundwater, but this may be industrial confounding. Breast cancer demonstrated a slight, but significant, risk associated with surface chlorinated water. This risk, however, might be due to confounding of rural life style, early childbearing and large families with nonchlorinated water found in these settings. Chlorination risk for kidney cancer was not significant. No risk was observed in association with surface water for other cancers of the gastrointestinal or urinary tract. Multiple myeloma was significantly associated with a risk from ground water.

Lung cancer mortality and residential proximity to industry.

A potential causal relationship has been suggested by other studies between air pollution and lung cancer. To attempt to define the risk of lung cancer associated with residential proximity to industry by type in Louisiana, lung cancer deaths occurring between 1960 and 1975 in residents of 20 parishes were compared to controls matched on age, sex, year of death and parish of residence. The comparisons were limited to cases (N = 1418) and controls (N = 1429) with known length of exposure to and residing within 0.99 mile (exposed and 1.0 to 3.0 miles (unexposed) radius of an industry type. Of the 13 industry types evaluated, the petroleum and chemical industries showed the highest consistent elevations in risk associated with closeness of residence to industry, whereas possible risks shown for food, grain, canning, and paper industries are less defined. For the petroleum industry, the risk was demonstrated in the group with 10 or more years of residential exposure to the industry in question. For the chemical industry, the residential risk was found in people employed in low risk occupations, who were exposed to large individual industries and was independent of length of exposure as determined for less or more than ten years, (RR = 4.5). The results suggest that residential proximity to petrochemical industries may make a contribution to the lung cancer mortality in Louisiana.

Treatment guidelines for HIV-associated wasting.

Patients with acquired immunodeficiency syndrome (AIDS) often suffer from weight loss manifested by a loss of body cell mass (BCM). The causes of human immunodeficiency virus (HIV)-associated wasting may include anorexia, malabsorption, and a variety of altered metabolic states. Malabsorption and diarrhea may result from gastrointestinal tract opportunistic infections or from direct effects of HIV on the gastrointestinal tract. Infection with HIV may produce metabolic derangements that alter nutrient utilization, resulting in loss of BCM. Nutritional assessment of the patient with AIDS should include an evaluation of BCM and physical and psychosocial functioning. Antiretroviral therapy and eradication of opportunistic infections do not always reverse wasting. Treatment should include nutritional counseling. Total parenteral nutrition is sometimes of benefit, particularly in patients with damaged gastrointestinal tracts. Dronabinol and megestrol acetate may promote weight gain; however, dronabinol may have adverse effects, and most of the gain with megestrol acetate is in fat rather than BCM. If gonadal dysfunction is present, testosterone replacement therapy should be included in the treatment plan. Some studies suggest that oral anabolic steroids may improve muscle strength and body composition. In randomized, placebo-controlled trials, mammalian-derived human growth hormone (rhGH[m]) has produced sustained weight and BCM gains in AIDS patients. If a patient continues to lose BCM after the above factors have been addressed and corrected, a 12-week course of rhGH[m] is indicated. Halting the progression of HIV-associated wasting may improve survival, enhance physical and social functioning, and enrich quality of life.

Cancer and drinking water in Louisiana: colon and rectum.

A case-control mortality study conducted in 20 parishes (countries) of South Louisiana to determine what relationship drinking Mississippi River water might have on mortality from colon or rectal cancer, found a significant risk for rectal cancer associated with surface water. Rectal and colon cancer deaths (692 and 1167) from 1969 to 1975 were matched to non-cancer deaths by age at death (+/- 5 years), year of death, sex and race, and within groups of parishes with similar industrial and urban-rural characteristics, each group being defined so as to ensure that it included as nearly as possible equal populations using water from ground and surface sources, based on the 1970 census. Colon cancer did not relate significantly to any water variable, but rectal cancer associated strongly with surface, or Mississippi River, water. The odds ratio for rectal cancer between those who were born and died on ground water was 2.07 with 95% C.I.: (1.49-2.88). A multi-dimensional contingency table analysis found the association between rectal cancer and surface water significant at the .0001 level and not dependent on age, race, sex or year of death. The risk for men was slightly higher than for women, but both sexes showed an increased risk. Chlorination also associated significantly with rectal cancer. Among those who used river water, the risk increased inversely as the distance from the mouth, with greater risk downstream from the many industries which line the river.

Double gloving. Protecting surgeons from blood contamination in the operating room.

Health care workers, particularly surgeons, understand the importance of preventing contamination from blood of patients infected with deadly viruses. One of the most common areas of contamination is the hands and fingers due to the failure of glove protection. There are varying opinions regarding the frequency of glove failure, the necessity of wearing two gloves for added protection, and the ability to operate when wearing two gloves. We performed a prospective, randomized, trial of 143 procedures involving 284 persons to answer these questions for surgeons and first assistants. Overall, the glove failure rate (blood contamination of the fingers) was 51% when one glove was worn and 7% when two gloves were worn. Acceptability was 88% in the group who agreed to wear two gloves, and 88% of these did not perceive that tactile sense was significantly impaired. We believe that double gloving should be, and can be, used routinely during major surgical procedures to protect surgeons from blood contamination.

Ocular disorders associated with a new severe acquired cellular immunodeficiency syndrome.

Among the prominent features of a newly described acquired cellular immunodeficiency syndrome that affects previously healthy male homosexuals are multiple opportunistic infections and Kaposi's sarcoma. Immunosuppression induced by cytomegalovirus infection may play a major role in the pathogenesis of this disorder. We have performed ophthalmic examinations on seven such patients and found ocular abnormalities in all cases. Six patients were examined during the course of their illness and one patient at autopsy only. Each patient had several cotton-wool spots in the affected eye. Other ocular findings included cytomegalovirus retinitis, severe retinal periphlebitis, and conjunctival Kaposi's sarcoma (one case each).

Cytomegalovirus retinopathy as the initial manifestation of the acquired immunodeficiency syndrome.

Of 100 consecutive patients with human immunodeficiency virus infection and cytomegalovirus retinopathy, 15 did not have a previous diagnosis of the acquired immunodeficiency syndrome before the ocular infection. All had other HIV-related disorders that would place them in Group IV of the Centers for Disease Control hierarchical classification system for HIV infections. In nine patients, cytomegalovirus retinopathy was the only disorder that fulfilled the Centers for Disease Control criteria for diagnosis of AIDS. In the other six, examination disclosed additional preexistent or concurrent nonocular disorders that were also diagnostic of AIDS. No demographic, medical, or ophthalmic characteristics distinguished the nine patients for whom cytomegalovirus retinopathy was initially the only manifestation of AIDS. On the basis of published figures for the prevalence of cytomegalovirus retinopathy in patients with AIDS, and the incidence with which HIV-infected persons develop AIDS, it is estimated that approximately 1.8% of patients with AIDS have cytomegalovirus retinopathy as the first manifestation and that less than 1% of HIV-infected persons will develop cytomegalovirus retinopathy as the initial manifestation of AIDS during the first seven years after infection with HIV.

Comparison of xenon arc and argon laser photocoagulation in the treatment of choroidal melanomas.

We analyzed the follow-up data in 38 consecutive patients with selected choroidal melanomas that were treated by photocoagulation between 1971 and 1980. Indications for treatment included photographic documentation of tumor growth or an unequivocally positive radioactive phosphorus uptake test, or both. Xenon arc photocoagulation was used in 22 patients (58%) and argon laser was used in 16 patients (42%). At the time of data analysis, the length of follow-up was at least 58 months in all patients. Although all treated tumors were initially eradicated according to ophthalmoscopic and fluorescein angiographic criteria, there was subsequent regrowth in three of the 22 patients (14%) treated with xenon photocoagulation and in ten of the 16 patients (64%) treated with argon laser. The recurrences were observed on an average of 71 months after completion of treatment in the xenon-treated group and on an average of 30 months in the argon-treated group. More treatment sessions were required in the argon laser group to achieve tumor control. Complications of vitreous hemorrhage, cystoid macular edema, and retinal detachment were greater in the xenon photocoagulation group.

Immunologic aspects of the acquired immunodeficiency syndrome and male homosexuality.

The acquired immunodeficiency syndrome (AIDS) is the most common and best characterized disorder of T cells leading to enhanced susceptibility to infection. Current hypotheses hold that infection with human T-cell lymphotropic virus type III/lymphadenopathy virus (HTLV-III/LAV) is a necessary but not a sufficient condition for the development of AIDS, and that a variety of cofactors participate in the pathogenesis of the syndrome. This article reviews the immunologic aspects of AIDS and the AIDS-related syndromes, as well as concepts of etiology and pathogenesis. Predisposing factors for this disease in the homosexual or bisexual host are emphasized.

Analysis of pain management in critically ill patients.

We analyzed the adequacy of pain control for 17 trauma patients during the initial part of their stay in the intensive care unit, and assessed reasons for inadequate analgesia, if it occurred. Patients, and physicians, and nurses were interviewed. A verbal pain intensity scale was used to determine whether patients received adequate analgesia. Patients were asked if the pain hindered their activities, and whether they requested pain medication from their caregivers. Caregivers were questioned whether patients received adequate analgesia. Prescribed morphine regimens and the amount of narcotic administered were analyzed. Twenty-seven percent of patients rated pain intensity as moderate and 47% as severe. Ninety-five percent of housestaff and 81% of nurses reported the patients received adequate pain control. Forty-seven percent of the patients who had moderate or severe pain asked their physician for more pain medication, and 65% asked the nurse. Thirteen residents did not order a larger dose of morphine due to concern about respiratory depression or hypotension. Morphine dosages ranged from 1-8 mg intravenously every 1-2 hours as necessary. Nurses administered less than the maximum amount ordered 58% of the time. The mean dosing interval was 2.3 hours. Barriers to adequate pain management were disparity in the perception of pain between patients and caregivers; patients not requesting more analgesia despite despite the presence of moderate to severe pain; and physician and nurse concerns about patients' adverse physiologic response to increased dosages.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

The relationship between adjusted hospital mortality and the results of peer review.

This study assessed the relationship between the Health Care Financing Administration adjusted mortality rate for a hospital and the errors in care found by the peer review process. The three data sets used were: (1) the 1987-1988 completed reviews from 38 peer review organizations (PROs) of 4,132 hospitals and 2,035,128 patients; (2) all 1987 hospital mortality rates for Medicare patients as adjusted by HCFA for patient mix; and (3) the 1986 American Hospital Association Survey. The PRO data were used to compute the percentage of cases reviewed from each hospital confirmed by a reviewing physician to have a quality problem. The average percentage of confirmed problems was 3.73 percent with state rates ranging from 0.03 percent to 38.5 percent. The average within-state correlation between the problem rate and the adjusted mortality rate for all PROs was .19 (p < .0001), but the correlations were much higher for relatively homogeneous groups of hospitals, .42 for public hospitals and .36 for hospitals in large metropolitan statistical areas (MSAs). These results suggest that the HCFA adjusted hospital mortality rate and the PRO-confirmed problem rate are related methods to compare hospitals on the basis of quality of care. Both methods may compare quality better if used within a group of homogenous hospitals.

Choroidal rupture and optic atrophy.

The association between post-traumatic optic disc pallor and traumatic choroidal rupture is poorly understood. To further define this relationship, nine cases of indirect traumatic choroidal rupture and post-traumatic optic disc pallor were compared with cases of indirect choroidal rupture without disc pallor in terms of severity of ocular injury, fundus findings, and visual outcome. The type and severity of the injury did not appear to influence the risk of optic disc pallor. Optic disc pallor was associated with a slightly poorer long term visual acuity than eyes without pallor (p = 0.059). The presence of a relative afferent pupillary defect was strongly associated with optic disc pallor (p = 0.016). Peripapillary retinal pigment epithelial abnormalities were a common finding, suggesting peripapillary trauma as a cause for optic disc pallor.