Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites

The antitumor effects of two polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when combined with cis-diamminedichlroplatinum (CDDP) or mitomycin C (MMC), were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO 1000 mg/kg and MGBG 50 mg/kg were given intraperitoneally for 6 successive days, while CDDP 3 mg/kg or MMC 2 mg/kg was given every second day. Although DFMO and MGBG plus MMC did suppress the tumor growth, the combination with CDDP led to no suppression, and rapid growth occurred after the cessation of therapy. The inhibition of tumoral DNA biosynthesis and a decline in polyamine levels, were also not observed. The polyamine antimetabolites when used with CDDP did not produce the desired antitumor efficacy, even though the platinum concentration in the tumor tissue was high. On the contrary, however, DFMO and MGBG when combined with MMC did suppress tumor growth, inhibited DNA biosynthesis, and tissue polyamine levels were low. These results suggest that though CDDP and MMC belong to a similar category of DNA attacking, bifunctional alkylating agents, the findings of these two drugs are contradictory. Here, the mechanism of action no doubt plays a contributory role.     

The Resource-Based Relative Value Scale. Toward the development of an alternative physician payment system

This article describes the design and methods of a study currently under way to develop a Resource-Based Relative Value Scale (RBRVS); an alternative basis for establishing the payment rate for the services and procedures (S/Ps) of physicians in medical and surgical specialties. Physician resource inputs to be measured include (1) S/P time, (2) pre-S/P and post-S/P times, (3) intensity, (4) practice costs, including malpractice premiums, and (5) the cost of specialty training. These five factors will be combined to produce an RBRVS denominated in nonmonetary units. In the initial phase of the study, data on time and intensity will be obtained through a national survey of physicians who perform these S/Ps. In the second, consensus phase of the project, the investigators will convene a panel of representatives of the medical profession, third-party payers, consumers, and other interested parties to examine areas of agreement and disagreement as to how an RBRVS should be used for policy purposes. The final results of this study are expected by the summer of 1988.     

Rapid diagnosis of pneumonia in children

Antigen detection techniques are available for the identification of bacterial polysaccharides, viruses, and chlamydia. Viruses and chlamydia are detected by direct immunofluorescence (DFA) or enzyme immunoassay (EIA). Bacterial polysaccharides are detected by latex agglutination or staphylococcal coagglutination of serum or concentrated urine. Most studies have not compared these techniques to the gold standard of lung puncture, so the role of dual infections with bacteria and viruses cannot be adequately determined. The sensitivity of any of these techniques is dependent on the quality of the antisera used. Monoclonal sera are now available for the detection of most viruses and seem to be as sensitive as polyclonal sera. DFA or EIA may offer equal sensitivity but their advantages and disadvantages must be considered by the local diagnostic laboratories. Most DFA and EIA systems have a sensitivity of 90% when compared with viral cultural for the identification of the organism. Agglutination reagents are available commercially for the detection of pneumococcal and Hemophilus influenzae type b polysaccharides. The sensitivity and specificity of each brand should be determined on serum or urine from patients known to have positive blood cultures and those free of disease. The brand chosen should be the one that has reasonable sensitivity and specificity. Rapid diagnostic techniques are helpful if they are used within a clinical context and they are positive. Negative tests do not rule out infection.     

Conceptual trends and issues in the psychotherapy of schizophrenia

A review of the theoretical principles of exploratory, insight-oriented psychotherapy of schizophrenia shows three major trends: drive theory, object-relations theory, and ego-psychology. These trends follow the development of psychoanalytic theory and may relate to symptom clusters of the illness. Current considerations of countertransference follow similar lines.     

Responses to tuberculin in the guinea-pig eye as a model of cell mediated immune responses in the external eye.

The clinical and histological findings in an animal model of ocular cell mediated immune responses are described. These were evoked in sensitised guinea-pigs by dropping tuberculin into the conjunctival sac or injecting it under the palpebral conjunctiva. When tuberculin was dropped into the conjunctival sac, higher doses were required to evoke a strong response than when it was injected subconjunctivally. When high doses of antigen were used for challenge, a mild response was observed in unchallenged contralateral eyes. The cellular response at low doses of tuberculin consisted predominantly of mononuclear cells. At higher doses the cellular infiltrate was more pronounced, and polymorphonuclear cells tended to predominate 24 hours after challenge, while at 48 hours mononuclear cells predominated.     

Assessment of closed head injury in trauma-related spinal cord injury

The complete medical records of 122 patients who sustained traumatic spinal cord injuries were reviewed to determine the frequency and results of emergency room assessments for loss of consciousness (LOC) and post-traumatic amnesia (PTA). Eighty-eight percent of the patients were assessed for LOC and 19% were assessed for PTA. Fifty patients (41% of the total population) admitted to LOC, PTA or both. Fourteen of these 50 patients underwent subsequent radiographic examinations of the skull, all of which were negative. Because of the association of intracranial complications and long-term cognitive sequelae with even brief LOC or PTA, early recognition of craniocerebral trauma is an important component of the acute management of spinal cord injured patients.     

C-reactive protein levels predict postoperative septic complications

We studied 108 patients undergoing clean-contaminated and dirty surgical procedures to determine whether daily C-reactive protein (CRP) measurements for 14 days postoperatively could predict the occurrence of septic complications prior to clinical diagnosis. Diagnostic criteria for septic complications and positive CRP response were defined in advance of the study. The CRP assays were carried out using an automated laser nephelometer system after the patient's discharge from the hospital. Forty-six septic complications were diagnosed in 40 patients. These complications consisted of wound infection (23), urinary tract infection (11), pneumonia (six), upper respiratory tract infection (three), intra-abdominal abscess (one), and other (two). The CRP testing was found to have a positive predictive value of 69% and a negative predictive value of 78%. We conclude that serial CRP measurements may be a valuable adjunct to surgical care in patients at high risk of postoperative septic complications.     

Polymorphonuclear leukocyte function in psoriasis vulgaris

Polymorphonuclear leukocyte (PMN) migration was assessed in vitro using the agarose plate method in patients with psoriasis vulgaris, and compared with an age- and sex-matched control group. No significant difference was found between the two groups in the PMN response to the chemotactic substances F-Met-Leu-Phe (FMLP) or zymosan activated serum (ZAS). Equally, the chemokinetic or chemotactic potential of psoriatic serum did not differ from control serum. Our results do not support a primary abnormality of PMN function in psoriasis.     

A national alcohol and trauma center survey. Missed opportunities, failures of responsibility

The results of a national survey of trauma centers concerning their assessment and response to the problem of alcohol and trauma are reported. Surveys were returned from 154 trauma centers located in 43 states and the District of Columbia. The profile of the 125,000 patients treated at the centers is a 30-year-old man sustaining blunt trauma, usually in a vehicular crash. Two-thirds of centers estimated that the majority of their patients had abused alcohol. While acknowledging alcohol as a significant cause of trauma, only 55.2% of centers routinely obtain admitting blood alcohol levels. Less than a third of the centers employ alcoholism counselors. Most trauma centers are not providing services that allow them to fulfill their responsibility to detect and initiate treatment of alcohol abuse, a major cause of traumatic injury.     

Inhibition of vessel allograft rejection by endothelial removal. Morphologic and ultrastructural changes.

The vascular endothelium plays an important and complex role in vascular allograft rejection. Antigens expressed by the endothelium can act to promote and be the target of rejection reactions, which often lead to thrombosis and ischemic necrosis of the allograft. In this study, segments of femoral artery and femoral vein with or without endothelium were grafted between allogenic or autologous control rats. Immunocompetent Lewis (RT1(1] recipient rats were randomly selected for groups (N = 14 for each) receiving the following: ACI- (RT1a) allografts with intact endothelium, allografts with endothelium removed before operation, autografts with endothelium, and autografts with endothelium removed. Rejection was assessed by graft patency as well as morphologic and ultrastructural changes. At 5 days, the allografts with intact endothelium were totally occluded, whereas allografts without endothelium remained patent, as did autologous control grafts with or without endothelium. Two additional groups (N = 14 each) receiving the de-endothelialized allografts or autografts were examined at 120 days after operation, revealing that grafts in both groups were still patent and had been re-endothelialized. These findings indicate that physical removal of vascular endothelium may depress vessel allograft rejection without immunosuppressive therapy.