Decreased lymphocyte adenosine deaminase activity in tumor patients.

Adenosine deaminase has been measured in the lymphocytes of individuals with various types of solid tumors. The mean activity was found to be significantly lower when compared with control individuals of a similar age.

Drug combinations in the treatment of gastric adenocarcinoma: a randomized Southwest Oncology Group study.

The FAM combination with the simultaneous administration of 5-fluorouracil, doxorubicin, and mitomycin C is considered standard chemotherapy for gastric adenocarcinoma. This study was initiated to determine whether a kinetically designed sequential administration of these three drugs would be superior and whether the presence or absence of easily measurable tumor would imply differences in survival. To do so, the Southwest Oncology Group tested two schedules in a randomized study of 239 patients. Independent judgments of response were made by two authors with the same results. Equivalent response rates (23% of all eligible sequential and 30% simultaneous) and median survival durations (22 and 23 weeks, respectively) were seen. Patients with and without readily measurable tumors each lived a median of 22 weeks. Higher degrees of hematologic toxicity were associated with prolonged survival (median 27 weeks versus 20 weeks, p = 0.04). Patients treated by community oncologists were described as having higher response rates than those treated in major medical centers (64% versus 31%, p = 0.03). The meaning of this is questionable in that there were no statistical differences in survival or toxicity. Those with prior exposure to 5-fluorouracil had only a tendency, without statistical significance, for a slightly inferior response and survival.

Autologous and allogeneic suppressor lymphocyte inhibition of human erythroid colony forming unit proliferation.

Certain in vitro and in vivo animal studies have supported the concept that lymphocyte-derived microenvironmental factors are important in erythroid proliferation. Considerable controversy has developed regarding the applicability of these concepts to human erythroid proliferation. We, therefore, evaluated the role of lymphocytes on human erythroid colony forming unit (CFUE) proliferation in the plasma clot system. Bone marrow (BM) was obtained from normal donors and cocultured with the following cell populations: a) cultured (6 day) lymphocytes autologous or allogeneic to BM; b) cultured lymphocytes stimulated with conconavalin A (Con A), allogeneic lymphocytes or streptokinase streptodornase (SKSD). In general, unstimulated cultured lymphocytes enhanced CFUE proliferation. In contrast, lymphocytes stimulated with Con A. SKSD, or allogeneic lymphocytes suppressed lymphocyte proliferation. The suppressor cell was concentrated in the T-cell fraction obtained by sheep red blood cell rosetting followed by ficoll-Hypaque centrifugation. Both allogeneic and autologous stimulated T-cells suppressed CFUE. Moreover, supernatants from stimulated lymphocyte cultures suppressed CFUE proliferation although the cell of origin and characteristics of the suppressive factors have not been defined. These data support the concept that lymphocytes may play an important role in modulating the human BM erythroid microenvironment.

Graduate medical education and rural health care.

Currently, residency training is neither detrimental nor helpful to the problems of rural health. Based on four generally accepted "truths" about rural health, medical schools should recruit students from rural areas, have them choose family practice as a career, and train them in rural settings. Given no substantial changes in residency training, the following recommendations are made. Develop a consensus definition of "rural." Educate rural communities to the purpose of residency training. Residency review committees should support rural rotations of at least six months; consider the number of residencies at a site irrelevant for accreditation; judge the quality of the product as the standard of accreditation; and define teaching competency by other than specialty label. All medical school departments should be involved in seeking solutions to the problems of rural health. New opportunities for funding of rural residency training should be sought. If major changes in residency training are possible, internal medicine, family practice, and pediatrics should merge as a single primary care specialty and for residency training. Only this residency should be considered primary care for residency reimbursement purposes, and only its graduates should be reimbursed for primary care services.

Cis-platinum plus high-dose methotrexate. Toxicity and efficacy in ovarian carcinoma.

Cis-platinum plus high-dose methotrexate with citrovorum factor rescue underwent an initial evaluation of toxicity in patients with pelvic or abdominal adenocarcinoma and a subsequent efficacy trial in proven ovarian cancers. Forty-five patients with advanced abdominal adenocarcinoma were evaluable for toxicity. Toxicity was minimal and was not exacerbated by the presence of effusions or by modestly compromised renal function. Twenty-six patients had definite ovarian primaries and were evaluable for efficacy. All but four were refractory to standard therapy. Seven achieved either complete response (four) or partial response (three). Four additional patients showed lesser, but clinically important, objective responses. Patients who had not received prior therapy all responded with three of the four attaining complete response lasting from 7-22+ months. This regimen is well tolerated and has definite tumoricidal activity even in heavily pretreated patients.

Phase II trial of methyl-GAG (NSC-32946) in squamous cell and adenocarcinoma of the lung.

Thirty-four assessable patients with advanced squamous cell and adenocarcinoma of the lung were treated with weekly MGBG in a phase II trial. Only one partial response, in adenocarcinoma, was observed. Myelosuppression was mild to moderate. Major toxicities consisted of myalgia, myopathy, mucositis, gastrointestinal and pronounced vasculitis in one patient. It would appear that MGBG does not have sufficient antitumor activity to warrant further investigation in advanced squamous cell and adenocarcinoma of the lung.

Systemic talc granulomatosis associated with disseminated histoplasmosis in a drug abuser.

A 32-year-old intravenous drug abuser was found to have systemic talc granulomatosis and disseminated histoplasmosis. The clinicopathologic findings of this case support the hypothesis that the patient was predisposed to disseminated histoplasmosis by repeated intravenous talc administration. The effects of silica, a close relative of talc, on macrophages and the role of macrophages in recovery from Histoplasma capsulatum infection are described.

Scabies associated with radiation therapy for cutaneous T-cell lymphoma.

Scabies, infection with Sarcoptes scabiei, is known to be predisposed to by poor body hygiene, environmental exposure, and systemic immunodeficiency. We report the case of an 83-year-old man with Sezary's syndrome who developed scabies limited to the skin of the upper chest, the same location where he had previously received electron beam radiation treatments for cutaneous T-cell lymphoma. Histologic and immunohistochemical studies demonstrated that sections of the previously irradiated right and left chest skin, compared to non-irradiated chest, abdominal, and leg skin, had infestation by scabies, diminished involvement by T-cell lymphoma, and notably reduced numbers of Langerhans cells. These findings suggest that the development of scabies may be predisposed to by local cutaneous radiation therapy, and that it may be mediated by local cutaneous immunodeficiency secondary to reduced numbers of Langerhans cells.

Effects of teacher assistance teams on special education referrals in elementary schools.

School-based problem-solving teams recently have received much attention as a possible support for children who are at risk for school failure and for over-referral to special education. However, no controlled studies of the effects of such teams on numbers of referrals for special education or for proportion of appropriate referrals for special education have been conducted. The lack of adequate research concerning school-based problem-solving teams, coupled with the widespread promotion of their use, suggests that further study of such teams is important. In this study, we investigated the effect of one team model, Teacher Assistance Teams, on special education referrals in elementary schools of a large urban district. To address limitations of previous research, schools with such teams were compared with those without across several years of implementation. Analysis yielded a significant decrease in referrals in both groups of schools but no significant differences between groups. These findings may be explained by the context in which both groups of schools functioned.

The use of failure mode effect and criticality analysis in a medication error subcommittee.

Failure Mode Effect and Criticality Analysis (FMECA) is the systematic assessment of a process or product that enables one to determine the location and mechanism of potential failures. It has been used by engineers, particularly in the aerospace industry, to identify and prioritize potential failures during product development when there is a lack of data but an abundance of expertise. The Institute for Safe Medication Practices has recommended its use in analyzing the medication administration process in hospitals and in drug product development in the pharamceutical industry. A medication error subcommittee adopted and modified FMECA to identify and prioritize significant failure modes in its specific medication administration process. Based on this analysis, the subcommittee implemented solutions to four of the five highest ranked failure modes. FMECA provided a method for a multidisciplinary group to address the most important medication error concerns based upon the expertise of the group members. It also facilitated consensus building in a group with varied perceptions.

T M J screening for orthodontics.

A crisis seems to be developing in the ongoing dilemma of the relationship of orthodontics to temporomandibular disorders. Articles in the lay and dental press bear out this increasing concern. This paper provides a six step TMJ screening process for all dental practitioners providing orthodontic services. Specialty licensed orthodontists as well as dentists providing orthodontics as a part of family practice will find these guidelines simple to incorporate into their clinical evaluations.

Assessment of temporomandibular injury and orofacial pain.

Every individual has physical faults which makes him less than a perfect biological specimen. This is the foundation for the legal "eggshell principal." Most of us do not have perfect skeletal formation, muscular adaptation, neurological or vascular systems. Additionally, we may not have complete symmetry and ideal form to our cranium or mandible. Our dentitions are imperfect. All of these imperfections play a role in every injury. The variances of normal that are seen in any medical or dental population, must be accepted; therefore, a given injury can have tremendously varied sequelae, depending on the person receiving it. The patho-physiology resultant from an accident may not parallel the severity of the motor vehicle accident, fall or blow. Prompt and proper evaluation of the individual-turned-patient is imperative. Referral to a dentist, competent in providing the necessary evaluation of the injury, is the responsibility of those individuals attending to the injured person's physical, emotional, and financial trauma. Their physician, dentist, attorney or counselor should take the responsibility of providing proper referral. The four most dangerous words in medicine and dentistry today are: "It Will Go Away." People often develop serious sequelae by assuming that their problem will "go away" by just leaving it alone long enough or by simply ignoring it. With proper evaluation and management, most trauma related temporomandibular injuries can be corrected or at least be properly managed.

Broad support evident for the emerging specialty of orofacial pain.

The emerging field of Orofacial Pain is being considered by the American Dental Association for full status as a new dental specialty. Many recent advances in the neuroscience of orofacial pain have lead to treatments by orofacial pain dentists that provide significant relief for patients with chronic orofacial pain disorders. However, access to this care has been limited leaving many patients to continue to suffer. Subsequently, recent efforts to improve this by developing the field into a specialty have shown broad support among dentists and increased awareness of the benefits this field can provide for dentists and their patients. A recent survey of 805 individuals in the general population who reported having a persistent pain disorder revealed that more than four out of 10 people have yet to find adequate relief, saying their pain is out of control-despite having the pain for more than 5 years and switching doctors at least once. "This survey suggests that there are millions of people living with severe uncontrolled pain," says Russell Portenoy, MD, President of the American Pain Society. "This is a great tragedy. Although not everyone can be helped, it is very likely that most of these patients could benefit if provided with state-of-the-art therapies and improved access to pain specialists when needed." (1). Development of the field of Orofacial Pain into a dental specialty has been motivated primarily by this issue; patients with complex chronic orofacial pain disorders have not been historically treated well by any discipline of health care. Recent studies of chronic orofacial pain patients have found that these patients have a high number of previous clinicians and have endured many years with pain prior to seeing an orofacial pain dentist (2) (Fig. 1). Complex pain patients and the clinicians who see them are often confused about whom they should consult for relief of the painful disorder. Treatment for these patients within the existing structure of dental or medical specialties has been inadequate and millions of patients are left suffering. Insurers are also confused with regard to reimbursement and make decisions to exclude treatment for orofacial pain disorders under both dental and medical policies. However, Dentistry has taken a leading role in health care to address this national problem by developing the field of Orofacial Pain into a dental specialty. A study of dentists and dental specialists have shown that there is a recognized need and broad support for further development of this field into a new dental specialty(3).