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Biomedical subjects

W D Johnson

Publications and source records attributed to W D Johnson.

At least 19 recordsLinked to original sources

Regression toward the mean in 2 x 2 crossover designs with baseline measurements.

Clinical trials often involve the study of patients whose values for some quantitative characteristic are in the extreme of the distribution for the normal population. Subsequent observation of the characteristic of interest will ordinarily tend to regress toward the mean of the distribution even in the absence of a treatment effect. We consider the impact of regression toward the mean in the analysis of data arising in 2 x 2 crossover trials with two baseline measurements. The usual summary statistics can be especially misleading in the presence of regression toward the mean.

Bias

Aspirin use and survival after coronary bypass surgery.

From Jan. 1, 1968, through Dec. 31, 1981, 5618 patients in a single cardiovascular surgery practice underwent coronary bypass surgery. Detailed clinical information was obtained during hospitalization and entered into a data base. All surviving patients were surveyed for aspirin use four times: in 1984, 1985, 1986, and 1987. A subgroup of 2395 patients gave consistent answers on every returned survey. The group that answered consistently "yes" had a 5-year survival rate of 79%; those who answered consistently "no" had a 5-year survival rate of 67%. Stepwise logistic regression showed that, after adjusting for patient characteristics, the relative risk of death was 58% (confidence interval 47% to 70%) for consistent aspirin users compared with consistent non-aspirin users. This study provides evidence that regular aspirin use after bypass surgery may enhance survival.

Actuarial Analysis

Immunologic markers of clinical evolution in children recently infected with Leishmania donovani chagasi.

The study attempted to identify immunologic markers for progression of Leishmania donovani chagasi infection to disease in children in an area endemic for visceral leishmaniasis (VL). [3H]thymidine uptake of lymphocytes stimulated with L. donovani chagasi antigen from children with asymptomatic infection (25,286 +/- 11,648) and from children with self-healing subclinical infection (15,511 +/- 4681) was greater (P = .001) than that observed with lymphocytes from children who progressed to classic VL (4811 +/- 2984). The interferon-gamma (IFN-gamma) levels from asymptomatic and subclinically infected children (74 +/- 90 units/ml) were higher (P = .02) than those observed in children who progressed to VL (7 +/- 8 units/ml). Absence of lymphocyte blastogenesis and IFN-gamma production were associated with progression of infection to classic VL. In the presence of these markers, children should be closely followed to identify signs and symptoms that would permit early initiation of therapy.

Adolescent

Surgical treatment of syringomyelia based on magnetic resonance imaging criteria.

The treatment of syringomyelia includes many surgical options. We report a retrospective study of 65 patients with cavitary lesions of the spinal cord in whom the results of magnetic resonance imaging were used to develop specific treatment strategies. Intramedullary cavities were classified into three general types: 1) communicating syrinxes, which occurred with hydrocephalus and were anatomically continuous with the 4th ventricle (9 patients); 2) noncommunicating syrinxes, which were separated from the 4th ventricle by a syrinx-free segment of spinal cord (42 patients); and 3) atrophic syrinxes, which occurred with myelomalacia (14 patients). Noncommunicating syrinxes were further subdivided according to type: Chiari II malformations with hydrocephalus (5 patients), Chiari I malformations without hydrocephalus (11 patients), extramedullary compressive lesions (12 patients), spinal cord trauma (6 patients), intramedullary tumors and infections (6 patients), and multiple sclerosis (2 patients). Of the 65 patients, 39 underwent surgical treatment for progressive symptoms. Syrinxes occurring with hydrocephalus were treated empirically with a ventriculoperitoneal shunt. Excellent results were achieved in 7 of 7 patients with communicating syrinxes and in all 5 patients with Chiari II malformations. Two approaches were used in the treatment of syrinxes occurring with Chiari I malformations: Posterior fossa decompression improved symptoms but did not reduce syrinx size in 2 of 3 patients. In the third patient and in 3 patients who were not treated with decompression, shunting from the syrinx to the cerebellopontine angle cistern collapsed the cavity and resolved symptoms over the interval of follow-up (average follow-up, 1.5 years). Excision of extramedullary obstructions at the rostral end of noncommunicating syrinxes resulted in collapse or disappearance of the cavity in 6 of 7 patients. The remaining patient was treated effectively by a syringocisternal shunt. In all 4 patients with posttraumatic syringomyelia, good results were achieved by a spinal or syringocisternal shunt. Syrinxes associated with intramedullary masses were managed by biopsy or excision of the causal lesion and appropriate adjunctive therapy (6 patients). Patients with atrophic syrinxes were not operated upon except to relieve symptoms referrable to the causal lesion (4 patients). Recurrent syrinxes were not encountered in the 35 surviving patients over an average follow-up of 2.5 years. It is concluded that syringomyelia is a complex pathological disorder with several mechanisms of pathogenesis that requires a number of different treatment strategies.

Adolescent

Syrinx shunt to posterior fossa cisterns (syringocisternostomy) for bypassing obstructions of upper cervical theca.

Syrinx shunts to the spinal subarachnoid space are likely to fail if the cerebrospinal fluid pathways rostral to the syrinx are blocked. To bypass obstructions at or below the level of the foramen magnum, a technique was developed for shunting the syrinx to the posterior fossa cisterns, termed "syringocisternostomy." Syrinxes were shunted to the cisterna magna in two patients with spinal arachnoiditis and to the cerebellopontine angle cistern in four patients with Chiari I malformations. There was symptomatic improvement and collapse of the syrinx in each case, with no complications or recurrences over a follow-up interval of 14 to 27 months (average 20.3 months). The surgical technique and results of treatment are described.

Adult

Fitting growth curve models to longitudinal data with missing observations.

We discuss the analysis of growth curve data with missing or incomplete information. The approach is to fit subject-specific models and then to carry out an analysis in terms of the estimated parameters. This achieves reduction of data and eliminates the need for special considerations for subjects with missing data. Although there is no perfect substitute for complete data, our approach provides a way to handle missing data using a straightforward application of well-known statistical methodology.

Cephalometry

Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs.

A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog.

Animals

Soluble IL-2 receptor as an agent of serum-mediated suppression in human visceral leishmaniasis.

In visceral leishmaniasis (VL), patient's lymphocytes are not activated by leishmania Ag stimulation, and their sera exhibit a potent nonspecific suppressive effect on the responses of normal lymphocytes. Sera were obtained from 33 VL patients, eight patients with subclinical VL, and from 27 normal volunteers. Only sera from VL patients markedly reduced Con A-induced lymphocyte proliferative responses, as well as IL-2 or IFN-gamma production by normal lymphocytes. Addition of exogenous human rIL-2 to cultures containing VL patient sera partially reversed the normal lymphocyte proliferative capacity and restored IFN-gamma production. This phenomenon was consistent with the presence of greatly elevated levels of soluble IL-2R (sIL-2R) in VL patients' sera (4299 +/- 2351 U/ml), well above those of normal sera (180 +/- 94 U/ml), or of sera from patients with subclinical leishmania infection without immunosuppression (1002 +/- 281 U/ml). Furthermore, the removal of sIL-2R reduced VL serum suppressive activity as evaluated by effects on IL-2 and on IFN-gamma production. These data suggest the participation of high levels of sIL-2R in the serum-mediated suppression in VL.

Concanavalin A

Effect of regression to the mean in the presence of within-subject variability.

Regression to the mean arises often in statistical applications where the units chosen for study relate to some observed characteristic in the extreme of its distribution. Gardner and Heady attribute the effect of regression to the mean to measurement errors. They assume the model Yi = U + ei, where U is a fixed within-subject component and ei is the random measurement error. They suggest several replicate measurements to reduce the regression effect under the assumption that the measurement errors ei are independent within subjects. While measurement errors play an important role in regression to the mean, one should not overlook within-subject variation. In this paper, we consider a model to estimate the regression effect in the presence of correlated within-subject effects as well as independent measurement errors.

Adult

A randomized controlled trial of allopurinol in coronary bypass surgery.

A plethora of experimental evidence indicates that allopurinol reduces the formation of cytotoxic free radicals during myocardial ischemia and reperfusion. The purpose of this study was to evaluate the effect of allopurinol on cardiac performance and early mortality after coronary bypass surgery. Allopurinol (n = 89) or placebo (n = 80) was administered to 169 patients before surgery. Randomization produced groups evenly matched for surgical risk factors. Hospital mortality rate in the placebo group was 14 of 80 (18%) in the allopurinol group 4 of 89 (4%), p = 0.014. Cardiac performance, scored by cardiac index and the need for ionotropic or mechanical support, was significantly better in the allopurinol group. More nonfatal complications occurred in the allopurinol group. When either a complication or death is termed an event, the proportion of events was equal in the two groups. No side effects were identified. We now administer allopurinol to all patients who are undergoing bypass surgery unless specifically contraindicated.

Adult

Predisposition to emotional distress and psychiatric illness amongst doctors: the role of unconscious and experiential factors.

This paper explores the contribution of unconscious and experiential factors in accounting for the high rates of depression, alcohol and drug abuse and suicide within the medical profession. The first part of the paper reviews the literature on motivations to study medicine and proposes that, for some doctors, a component of their decision is a response to unconscious drives to compensate for childhood experiences of parental impotence, or emotional neglect. The second part of the paper utilizes the theoretical framework of Kohut to argue that these childhood experiences may also result in the development of a narcissistic disturbance, and a vulnerable self-esteem. A model is outlined of how this may contribute to the development of emotional distress and psychiatric illness through the creation of a state of dependence on patients, emotional detachment and the denial of personal vulnerability. It is proposed that preventative strategies will need to include changing the emotionally 'abusive' nature of medical education, which tends to exacerbate this process.

Affective Symptoms

Isospora belli infections.

I. belli is common in tropical and subtropical environments. Sporadic outbreaks have occurred in mental institutions and in day-care centers in the United States. The infection is common in immunosuppressed patients, particularly those with AIDS living in tropical areas. Transmission probably occurs by the fecal-oral route. Chronic diarrhea is the major clinical manifestation. The pathophysiology of I. belli-induced diarrhea is unknown. Laboratory diagnosis is readily performed with the examination of unstained and stained stool specimens particularly by the modified Ziehl-Nielsen method. I. belli infection responds promptly to trimethoprim-sulfamethoxazole therapy and recurrent disease can be prevented with either trimethoprim-sulfamethoxazole or pyrimethamine-sulfadoxine.

Animals

A case-control study of serum vitamins A, E, and C in lung cancer patients.

In a case-control study, serum levels of vitamins E, C, and A, carotenoids, total cholesterol, and retinol-binding protein along with smoking levels were studied on 59 persons newly diagnosed with lung cancer and also on matched hospitalized controls. The relative risk for smoking increased with the number of pack years of cigarettes smoked. Cases had significantly lower serum levels of carotenoids, vitamin E, and total cholesterol. Adjustment for serum cholesterol levels diminished the case-control difference for serum carotenoid levels and reduced the case-control difference for serum vitamin E levels. The results indicate that serum vitamin E may also be associated with lung cancer, possibly to a greater degree than serum retinol (vitamin A) is associated with lung cancer.

Aged

Prevalence of HIV infection and high-risk activities in Haiti.

The prevalence of antibodies to human immunodeficiency virus (HIV) was determined in the relatives, friends, and sex partners of AIDS patients in Haiti and in other unrelated Haitian population groups. Among contacts of AIDS patients, HIV seroprevalence was highest among sex partners of the opposite sex (55%) and lowest among female relatives and friends (9%) of female AIDS patients. Male relatives and friends of male AIDS patients had a seroprevalence rate of 19% and also had a history of multiple heterosexual partners and frequent contact with prostitutes. The HIV seroprevalence rate among unrelated groups of Haitian adults ranged from 2% in rural healthy adults to 22% among tuberculosis patients to a high of 49% among Haitian prostitutes. This seroprevalence pattern suggests that HIV infection is widespread in Haiti and that heterosexual activity plays a major role in transmission.

Bisexuality

Treatment and prophylaxis of Isospora belli infection in patients with the acquired immunodeficiency syndrome.

Enteric infection with the protozoan Isospora belli is common in patients with the acquired immunodeficiency syndrome (AIDS) and causes severe diarrhea. I. belli responds well to treatment with trimethoprim-sulfamethoxazole, but there is a high rate of recurrence. To investigate the effect of long-term prophylaxis, we studied 32 Haitian patients with AIDS complicated by I. belli infection and chronic diarrhea. All were treated with trimethoprim (160 mg) and sulfamethoxazole (800 mg), given orally four times a day for 10 days; the patients were then randomly assigned to receive 500 mg of sulfadoxine and 25 mg of pyrimethamine weekly, 160 mg of trimethoprim and 800 mg of sulfamethoxazole three times a week, or placebo. Half of the patients (5 of 10) who received placebo had recurrent, symptomatic isosporiasis a mean of 1.6 months after the initial treatment. All 22 patients who received either trimethoprim-sulfamethoxazole or sulfadoxine-pyrimethamine remained asymptomatic. I. belli was identified in the stools of only one of these patients, who was receiving trimethoprim-sulfamethoxazole. The study medications were generally well tolerated but had to be discontinued in the cases of two patients because of severe pruritus. In 10 patients, the prophylactic regimen has been continued for a mean of 16 months without recurrent isosporiasis. We conclude that isosporiasis in patients with AIDS can be treated effectively with a 10-day course of trimethoprim-sulfamethoxazole and that recurrent disease can subsequently be prevented by ongoing prophylaxis with either trimethoprim-sulfamethoxazole or sulfadoxine-pyrimethamine.

Acquired Immunodeficiency Syndrome

Pruritic skin lesions. A common initial presentation of acquired immunodeficiency syndrome.

During July 1983 to December 1984, we observed that 62 (46%) of 134 Haitian patients with acquired immunodeficiency syndrome had intensely pruritic eruptions for which neither specific causative nor categoric diagnoses could be established. These lesions were a presenting manifestation of acquired immunodeficiency syndrome in 79% of the patients and appeared a mean of 8 months before the diagnosis of either Kaposi's sarcoma or opportunistic infection. Lesions included erythematous round macules, papules, or nodules that first appeared on the extensor surface of the arms, but subsequently involved the legs, trunk, and face. Histologically, the lesions were characterized by varying degrees of mixed (predominantly eosinophilic) perivascular and perifollicular inflammatory cell infiltrates of the dermis. The lesions did not respond to any therapeutic regimens used and usually persisted throughout the acquired immunodeficiency syndrome illness. Demographic and laboratory data did not distinguish these patients from those without pruritic skin lesions.

Acquired Immunodeficiency Syndrome