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Elderly patients can remain in acute care hospitals for protracted periods of time waiting for transfer to long-term care facilities. Because such patients no longer require acute care services, hospitals often fail to provide programs for them and staff may experience them as inappropriate. This study provides a descriptive understanding of these patients and examines factors associated with length of stay. Although differences were found between patients who were discharged in 6 months or less and those who remained in hospitals longer than 6 months, no significant differences were found among patients who remained for varying lengths of time beyond 6 months. Impact of long stay on patients and families is explored and implications for social work practice and discharge planning are examined. [ABSTRACT FROM AUTHOR]

A large body of research reveals the contribution of families to the care of elderly and health-impaired community-dwelling individuals. Less is known about the contribution of families to the provision of care following the admission of elderly relatives to a long-term care institution. Still less is known of the experience of elderly wives following the institutionalization of their husbands. The purpose of this paper is to increase nurses' awareness, through a review of the literature on family caregiving in later life, of the contribution to care made by elderly wives following the institutionalization of their husbands. We also hope to provide direction for clinicians with respect to the needs and concerns of wives, particularly at the time of, and following, the admission of their husbands to long-term care institutions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the visiting experience of wives whose husbands had been admitted to a long-term care institution. The study employed a longitudinal and prospective design and combined qualitative and quantitative approaches. The data were drawn from a larger study designed to explore the transition to quasi-widowhood. This article reports on one aspect of spousal caregiving following the admission of a husband to a long-term care setting, i.e. visiting. In this study, wives visited frequently. Their reasons for visiting included love and devotion, duty and obligation, the monitoring of husbands' well-being and the provision of assistance to both husbands and staff. They engaged in task performance and social interaction during visiting. Their feelings of satisfaction and enjoyment with visiting were associated with their husbands' well-being and feeling useful. Over the 9-month period of the study, two patterns of visiting and involvement emerged that were associated with different outcomes related to depression, morale and satisfaction with institutional dimensions of care. [ABSTRACT FROM AUTHOR]

This article considers, for a Canadian national probability sample of middle-aged women and men, the question of how typical is the experience of being 'caught in the middle' between being the adult child of elderly parents and other roles. Three roles are examined: adult child, employed worker, and parent (and a refinement of the parent role, being a parent of a co-resident child). Occupancy in multiple roles is examined, followed by an investigation of the extent to which adults in various role combinations actually assist older parents and whether those who provide frequent help are also those 'sandwiched' by competing commitments. The majority of middle-aged children do not provide frequent help to parents. Notably, the highest proportion of daughters who assist elderly parents are those in their fifties whose children are no longer co-resident. For both sons and daughters, being 'caught in the middle' is far from a typical experience in this cross-sectional analysis. [ABSTRACT FROM AUTHOR]

Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16 Hi ) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16 Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16 Hi Vδ2 T cells as a viable therapeutic option for cancer treatment., (© 2023. The Author(s).)

Introduction: Fontan patients have variable exercise capacity. Contemporary understanding as to which factors predict high tolerance is limited., Methods: Records from the Ahmanson/University of California, Los Angeles Adult Congenital Heart Disease Center were reviewed for adult Fontan patients who underwent CPET. Patients were considered "high performers" if their maximum oxygen uptake (VO 2 max/kg)-predicted was greater than 80%. Cross-sectional clinical, hemodynamic, and liver biopsy data was gathered. High-performers were compared to control patients across these parameters via associations and regression., Results: A total of 195 adult patients were included; 27 patients were considered "high performers". They had lower body mass indices (BMI, p < 0.001), mean Fontan pressures (p = 0.026), and cardiac outputs (p = 0.013). High performers also had higher activity levels (p < 0.001), serum albumin levels (p = 0.003), non-invasive and invasive systemic arterial oxygen saturations (p < 0.001 and p = 0.004), lower New York Heart Association (NYHA) heart failure class (p = 0.002), and were younger at Fontan completion (p = 0.011). High performers had less severe liver fibrosis (p = 0.015). Simple regression found Fontan pressure, non-invasive O 2 saturation, albumin level, activity level, age at Fontan surgery, NYHA class, and BMI to predict significant changes in VO 2 max/kg %-predicted. These associations persisted in multiple regression for non-invasive O 2 saturation, NYHA class II, activity level, and BMI., Conclusions: Thin Fontan patients who exercise more had better exercise capacity, Fontan hemodynamic profiles, and less liver fibrosis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we outline the unique features of different subsets of human γδ T cells and their antitumor properties. We also summarize the past and the ongoing pre-clinical studies and clinical trials utilizing γδ T cell-based cancer immunotherapy.

Background: Infliximab (IFX) discontinuation is not uncommon during the first year of treatment due to inadequate drug concentrations and anti-IFX antibodies (ATI). Both combination therapy and proactive therapeutic drug monitoring (pTDM) are used to decrease ATI and increase IFX durability. We proposed that monotherapy (Mono) is as effective as combination therapy (Combo) if the first maintenance infusion is dosed based on week 10 pTDM., Methods: In a retrospective cohort of 83 patients with inflammatory bowel disease (IBD), we examined the frequency of IFX discontinuation, ATI, infusion reactions, and IFX concentrations during the first year of treatment in patients receiving week 10 pTDM-guided IFX monotherapy (Mono pTDM; n = 16) compared with patients on mono (n = 32) or combination therapy (n = 35) in whom TDM was introduced at or after week 14, per standard of care (SOC)., Results: The frequency of IFX discontinuation was lower with Mono pTDM compared with Mono SOC (P = 0.04) but did not differ with Combo SOC (P = 1). At first TDM, no patient in the pTDM strategy had ATI, vs 41% in Mono SOC (P = 0.002) and 6% in Combo SOC (P = 1). Of the 13 subjects with ATI in Mono SOC, 7 (47%) had ATI already at week 14. IFX trough concentrations with Mono pTDM were higher during maintenance compared with Mono SOC (9.5 vs 6.4 µg/mL, P = 0.04) but not Combo SOC., Conclusions: Infliximab durability did not differ between patients on IFX monotherapy dosed based on p-TDM and patients receiving combination therapy. In the absence of concomitant immunosuppression, proactive TDM may improve IFX durability by maintaining higher IFX concentrations entering into maintenance. Further studies are needed to confirm our findings.

Background: Low infliximab (IFX) trough levels and high anti-infliximab antibodies (ATI) levels are associated with loss of response to IFX. Optimizing IFX levels to maintain target concentrations before loss of response may improve long-term efficacy. We hypothesized that trough levels at week 14 are predictive of IFX durability., Methods: A prospective observational cohort of pediatric patients with inflammatory bowel disease initiating IFX had IFX and ATI levels drawn at weeks 14 and 54. Primary outcome was week 54 persistent remission (PR), defined as clinical remission without IFX dose intensification. Univariate analyses tested associations of week 14 IFX (IFX14) and ATI (ATI14) levels, clinical and laboratory data with week 54 outcomes. Receiver operating curve analysis and positive and negative predictive values for IFX14 cut-off points were examined., Results: Of 58 patients enrolled, 8 (13%) stopped IFX before week 14 and 4 discontinued IFX between weeks 14 and 54. IFX14 level (P = 0.03), baseline C-reactive protein (CRP) level (P = 0.01), and week 14 CRP (CRP14) level (P = 0.0001) were associated with PR. A model with IFX14 levels predicting PR had an area under the receiver operating curve of 0.68 and a model with both IFX14 level and CRP14 >1.0 mg/dL had an area under the receiver operating curve of 0.74. IFX14 cut points of >3, >4, and >7 µg/mL had positive predictive values of 64%, 76% and 100%, respectively, for predicting PR., Conclusions: Both IFX levels and CRP at week 14 were significantly associated with week 54 efficacy. A model combining both CRP and IFX at week 14 may help predict remission at week 54.

This paper utilizes Helena Znaniecka Lopata's concept of life frameworks as a lens through which to understand the experience of widowhood amongst elderly Chinese immigrant women living in Toronto, Canada. While Lopata defined life frameworks as including social supports, social relations and social roles, for these widows, personal resources (framed in Chinese cultural context) were also important aspects of life frameworks. In-depth interviews with 20 widows contacted through a Chinese community center were conducted in Mandarin and Cantonese and then transcribed and interpreted through team-based qualitative analyses. These women ranged in age from 69 to 93 years and had been in Canada an average of 17 years, with over half of them widowed following immigration. Our analysis framed the widows' narratives in terms of four types of supports defined by Lopata: social, service, financial and emotional supports. They had fairly extensive social and service supports focused primarily around family and the Chinese community. Although norms of filial piety traditionally dictate sons as primary supports, daughters predominated as providers of supports to these widows. Interpreted from a life course perspective, financial supports were deemed sufficient, despite overall limited financial means. Emotional support was more nuanced and complex for these widows. Loneliness and feelings of social isolation were prevalent. Nevertheless, themes of acceptance and satisfaction dominated our findings, as did reciprocity and exchange. The narrative accounts of these widows depict a complexity of experience rooted in their biographies as Chinese women and as immigrants, rather than primarily in widowhood itself., (© 2013.)

While concern has been expressed for some time about the impact of rising female employment on informal help to older adults, few studies have directly compared employed and not-employed women and only rarely has research utilized national, population-based samples. This article examines whether paid employment reduces the provision and/or the intensity of specific types of help offered by women to older parents and parents-in-law. Data were drawn from the 1996 General Social Survey of Canada and consist of a sub-sample of women aged 40 to 64 who had at least one parent or parent-in-law alive. The independent variable is employment status (full-time, part-time, not employed). Dependent variables are type of help (meal preparation, cleaning, home maintenance, grocery shopping, transportation, banking and money management, personal care) and intensity of help. Two additional types of help examined are emotional support and checking up or monitoring. The analysis shows that employed daughters and daughters-in-law are less likely than those who are not employed to provide help with banking or bill paying but no differences are found on other types of help. Employment status is not significantly related to the total amount of time spent helping older parents and parents-in-law, although not-employed women spend more time helping with meal preparation. Women employed part-time are less likely to provide emotional support to a parent or parent-in-law. There are no differences by employment status in the likelihood of checking up on or monitoring the parent's or parent-in-law's situation. It is concluded that, on the whole, in the domains measured in this study, employment does not reduce women's provision of help to parents and parents-in-law.

Purpose: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy., Methods and Materials: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation., Results: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient., Conclusions: Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.

Factors contributing to depressive symptoms in a group of 67 family caregivers of hospitalized "long-stay" patients were investigated. Levels of depressive symptoms were quite high and were related to level of patient dependency, caregiver's health, feeling too many demands were being made on the caregiver, feeling torn between the patient's needs and the caregiver's own needs, not getting enough rest, amount of time spent in caregiving activities, feeling someone else could take over caregiving if necessary, and perceptions of staff. The factors contributing to depressive symptoms differed among spouses, children and other caregivers, but for all the strongest contributor was experiencing difficulty with staff.

Mutations in the serum protein transthyretin (TTR) cause amyloidosis involving the peripheral nerves, heart, and other organs. In Ashkenazic Jews, the only TTR variant described to date has been TTR Ile 33. We have studied DNA from another Ashkenazic Jewish kindred with familial amyloidotic polyneuropathy. Single-strand conformation polymorphism analysis, DNA sequencing, and restriction analysis indicated that this kindred has the TTR Pro 36 variant, previously described only in a Greek kindred.

There are no specific chromosomal abnormalities associated with refractory anemia with excess blasts in transformation [RAEB-T]. An 80-year-old white male with RAEB-T was found to have trisomies of chromosomes 8 and 11, i.e., 48,XY,+8,+11. To our knowledge, this chromosomal abnormality in RAEB-T has not been previously reported.

We treated 20, steroid resistant or steroid dependent and cyclophosphamide or chlorambucil treated, relapsing nephrotic patients with oral cyclosporine A for eight weeks. Cyclosporine A was started at 7 mg/kg/day and titrated to maintain HPLC level of 100 to 200 ng/ml. Of 20 patients, 14 had a complete remission and the remaining 6 had a reduction in their proteinuria. The mean serum albumin of the 14 responders rose from 2.1 g/dl to 4.1 g/dl (P less than 0.00001) after cyclosporine A therapy. The mean serum cholesterol of the 14 responders decreased from 394 mg/dl to 184 mg/dl (P less than 0.0001) after cyclosporine A therapy. The mean creatinine clearance of the 20 patients (104 ml/min/1.73 m2) was unchanged (107 ml/min/1.73 m2) after eight weeks of cyclosporine A. By life table analysis, 40% of the responders show a sustained remission of up to a year. Cyclosporine A responders had a higher T3 cell count prior to therapy compared to nonresponders (69 +/- 5.54% vs. 61 +/- 6.4%, P less than 0.02). Pre-therapy interleukin-2 levels measured in 10 patients were normal or supranormal in 8, 6 of whom were treatment responders. Two patients with low interleukin-2 levels were nonresponders. Cyclosporine A can be used to induce a remission in relapsing nephrotic patients, and short-term cyclosporine A therapy does not produce nephrotoxicity.

This study was aimed at purifying the progenitors of erythroid burst units (BFU-E) from human peripheral blood. Human mononuclear leukocytes from five normal donors were fractionated into several mononuclear cell subpopulations, including null lymphocytes with (null Fc+) and without (null Fc-) receptor for the Fc fragment of immunoglobulin G, through a succession of rosetting procedures and discontinuous Ficoll-Hypaque gradient centrifugations. The fractionated cells were separately cultured for 14 days in plasma clots in the presence of erythropoietin. Among fractionated cell subpopulations large and numerous BFU-E derived colonies grew only from the Fc- null lymphocyte subpopulation. This fraction, representing less than 4% of all mononuclear cells, also contains cells (42 + 11%) capable to differentiation towards the B-cell and plasma-cell lineages. The Fc+ null lymphocytes, representing less than 9% of all mononuclear cells, contained 15.2 + 3.3% cells capable of differentiation toward the T-cell lineage. The whole null lymphocyte subpopulation generated half the number of BFU-E colonies expected from its content in Fc- null lymphocytes. These data demonstrate that the progenitor of erythroid cells (BFU-E) resides in a small heterogeneous null Fc- subpopulation of circulating lymphocytes and suggest that its in vitro differentiation, though generally subjected to inhibitory and enhancing influences from other circulating cell subpopulations, does not necessarily require interaction with other peripheral blood cells.

Immunoreactivity for AA protein was rarely detected in briefly fixed amyloid of senile plaques and dyshoric angiopathy, but was not observed in Congophilic angiopathy. Plaque and dyshoric amyloid exhibited variable sensitivity to permanganate oxidation; Congophilic angiopathy was resistant to oxidation. In contrast to systemic amyloid composed of AA protein, the rare immunoreactivity of senile cerebral amyloid was lost with prolonged fixation. This study demonstrates that the fibrillar protein of senile cerebral amyloid differs from that of systemic amyloid of AA type.

Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas.

Serum amyloid A (SAA) protein is a 12,000 dalton protein that exists in serum under physiologic conditions as an 85,000 dalton complex and under certain conditions, as a 170,000 dalton component. To study the reason for this finding, the behavior of 125I-SAA was studied in the presence of cold SAA and several serum proteins. SAA caused a shift of some of the radioactivity to the region of albumin. Addition of normal human serum or albumin caused a shift of a significant fraction of the radioactivity to a peak eluting slightly ahead of albumin (80.000 daltons). This interaction could be blocked by the addition of cold SAA. No shift was noted when IgG or Bence Jones proteins were added. Thus, it appears that low molecular SAA protein has a tendency to aggregate with itself and to bind to albumin but not to human IgG or Bence Jones proteins.

In the current literature on parent care, the assertion is made that modern women at some time in their lives may expect to be sandwiched between responsibilities to old parents and their other commitments. This article presents the distribution for a random sample of 163 women aged 40 to 69 with respect to combinations of variables or commitment configurations that have been identified in the literature as contributing to women's being "caught in the middle." In addition, the lifetime caregiving experiences and the likelihood that those who have not yet been caregivers will be "caught" are examined for a subsample of the women. The argument is made that adult children rather than caregivers to frail parents are the appropriate population on which to focus if the incidence and prevalence of the involvement of adult children in parent care are to be ascertained.

Three patients receiving diphenylhydantoin (DPH) were seen with a reversible process suggesting mycosis fungoides. Clinical and laboratory manifestations included generalized pruritic exfoliative erythroderma, eosinophilia, lymphadenopathy, hepatosplenomegaly, circulating Sézary cells, epidermal Pautrier's microabscesses on skin biopsy, and moderate liver dysfunction. Studies of the distribution and function of the various lymphocyte subpopulations from these patients showed: (1) an increase in the relative and absolute number of T lymphocytes (85--92%); (2) significant stimulation of lymphocyte-blastic transformation by DPH and low response to pokeweed mitogen stimulation; (3) the impaired ability of T gamma lymphocytes to suppress B-cell differentiation and immunoglobulin production. With only one exception, 15 symptom-free patients on DPH showed none of these abnormalities. The clinical manifestations and immunologic abnormalities of patients with this pseudo mycosis fungoides syndrome remitted three to four weeks after DPH administration was discontinued. The proliferation of T lymphocytes and the inhibition of the function of T gamma-suppressor lymphocytes noted in these patients may be significant to the development of other types of pseudolymphoma and to that of true lymphoma.

Using the radioactively-labeled alkaline-degraded acid-soluble fraction of amyloid ([ 125I ]DAA), we developed a radioimmunoassay for the previously described amyloid-related component of the human serum (SAA). Screening the sera of 228 normal individuals and of 297 patients with a variety of illnesses, we found that SAA is a component of all human sera, including cord blood (mean 94 plus or minus 57 ng/ml). The concentration of this component increases significantly with the aging process, reaching very high levels in the eighth and nine decades. It is also elevated in all cases of amyloidosis (except for those associated with nephrotic syndrome) as well as in many patients with myeloma, macroglobulinemia, lymphoma, carcinoma, rheumatoid arthritis, and tuberculosis. A marked increase was noted in the early stages of a variety of acute inflammatory and infectious states with a return to normal levels paralleling clinical improvement and faster than the erythrocyte sedimentation rate. The possible implications of this component in the genesis of amyloid and in the immune process are discussed.

A patient is described with Gardner's syndrome manifested initially by an extra-abdominal desmoid which was resected. The case was complicated by metastatic adenocarcinoma of the colon and recurrence of several large painful desmoid lesions. In view of the predilection of desmoids to occur in women in their childbearing years, it was decided to treat these painful lesions with an anti-estrogen, tamoxifen (20 mg orally, four times daily). This therapy led to a complete relief of pain within 1 week and a progressive decrease in the size of the desmoid tumors to less than 50% of their initial volume by the end of the second week. Unfortunately, the patient's metastatic adenocarcinoma progressed and was complicated by sepsis leading to her death. This case suggests that the growth of desmoid tumors is under hormonal influence, a suggestion which deserves further investigation.

The level of serum amyloid A, a protein previously found to behave as an acute-phase reactant, was measured by a radioimmunoassay in 621 patients with various neoplastic diseases free of inflammatory processes. In all but eight of the 289 patients with solid tumors with distant metastases, in all patients with myelocytic leukemia with high leukocyte counts, and in all patients with advanced lymphoma, the serum amyloid A level was above 400 ng/mL. It was below this value in all tested patients with lymphocytic leukemia and in 250 of 270 patients with solid malignant tumors with localized or regional disease. Among the 20 patients from this latter group with levels higher than 400 ng/mL, 16 developed distant metastases within 214 days from the initial measurement. The serum amyloid A level decreased significantly in patients with lymphoma and those with metastatic solid tumors who responded to chemotherapy. Thus the level of serum amyloid A can be used as a biochemical marker that discriminates between disseminated and localized or regional disease, and monitors the response to therapy.

We treated 20 steroid-resistant or steroid-dependent nephrotic patients with oral cyclosporin for 8 weeks; they had been treated previously with cyclophosphamide or chlorambucil. Cyclosporine was started at 7 mg/kg/d and titrated to maintain a serum level of 100 to 200 ng/mL. Of 20 patients, 14 had a complete remission and the remaining six had a reduction in their proteinuria. By life table analysis, 40% of the responders show a sustained remission of up to a year. Pretherapy levels of interleukin 2, measured in 10 patients, were normal or supranormal in eight, six of whom were treatment responders; two patients with low levels of interleukin 2 were both nonresponders. Cyclosporine can be used to induce a remission in relapsing nephrotic patients, and short-term cyclosporine therapy does not produce nephrotoxic effects.

Cellular-mediated immunity was examined in 6 consecutive patients with active SLE, 6 patients with low active SLE 6 patients with DLE, 8 patients with other collagen diseases, and 9 healthy controls. The following parameters were measured: delayed hypersensitivity, in vitro lymphocyte blast transformation, and MIF production after stimulation with five common antigens, DNA, and two nonspecific mitogens (PHA, PWM). The 6 active SLE patients were anergic and had a markedly depressed response in vitro to the specific antigens and PWM (P less than 0.001). When CMI was retested in 5 patients as early as 5 days after the start of prednisone (60 mc/day), the results were significantly improved in 4 who also improved clinically, and they remained unchanged in a fifth patieht who failed to improve. There was a less marked impairment of CMI among the low active SLE group, whereas the DLE and OCD patients did not differ significantly from the control subjects. DNA did not cause significant stimulation of blast transformation in any of the study groups.

Serum SAA concentration was determined by radioimmunoassay in 21 Polish children with amyloidosis secondary to juvenile rheumatoid arthritis (JRA). The results were compared to controls and children with JRA in Polish populations (where amyloidosis is a frequent complication of JRA) as well as to American children with JRA (where amyloidosis in JRA has been observed only sporadically) and American control children. No significant differences of SAA protein levels were found in the amyloidotic Polish children when compared to JRA Polish and American children. However, significantly higher levels of SAA protein were present in amyloidotic Polish children when compared to the control Polish and American group. High serum SAA protein concentration in JRA children did not necessarily correlate with the presence of secondary amyloidosis. Other mechanisms are probably involved in the development of amyloidosis.

A 12,000 dalton serum amyloid A protein (SAA) has been isolated by chromatography on Sephadex in 10% formic acid. It is similar immunologically to the previously characterized 8500 dalton tissue amyloid A (AA) protein. The results of amino acid analyses, peptide maps, and the identity of the first 11 residues of the SAA and AA proteins support the idea that AA represents the amino terminal fragment of SAA and is derived from it by proteolysis.

This study was designed as a Phase II clinical trial in advanced recurrent or metastatic squamous cell carcinoma of the cervix with a combination of bleomycin (B: 10 u/m2/d) and cisplatin (P: 20 mg/m2/d) administered for five consecutive days in intravenous infusion for 7 hours and vincristine (V: 1 mg/m2) and methotrexate (M: 40 mg/m2) administered only on day one of each cycle which was repeated every 28 days up to a maximum of 6 times. Over a period of 2 years, 15 evaluable patients with measurable disease received at least 3 courses of therapy. Six had recurrent disease and nine had distant metastases. All had previous radiation therapy. There were two dropouts after the first course due to nausea and vomiting which was practically universal. Other side effects included: mild paresthesias of the extremities (89%), stomatitis (41%), diarrhea (17%), moderate pancytopenia and hypomagnesemia which was reduced from 65% to 17% when magnesium sulfate 10% was administered with cisplatin. Sixty-six percent of the evaluable patients achieved remission (7 partial and 3 complete) usually before the fourth course of therapy. The disease-free interval was of 29.7 +/- 15 weeks in all responders (40.6 +/- 15.5 weeks in complete responders). The mean survival from the start of BPVM therapy was of 55.8 +/- 33.3 weeks in responders and of only 14 +/- 2.9 weeks in nonresponders (P less than 0.01). It is concluded that BPVM is an effective combination chemotherapy in advanced squamous cell carcinoma of the cervix. These results should be confirmed in a Phase III trial.

In this study the presence of an amyloid A, antigenically related material was determined in four subpopulations of human leukocytes. Monocytes, granulocytes, thymus-derived lymphocytes, and bone marrow-derived and null lymphocytes were isolated from the peripheral blood of five apparently normal subjects, two patients with secondary amyloidosis, three patients with acute infections, and seven patients with metastatic cancer. Mononuclear leukocytes, isolated from the interface of a Ficoll-Hypaque gradient, were separated into monocytes, thymus-derived lymphocytes, and bone marrow-derived plus null lymphocytes by glass adherence and depletion of sheep erythrocyte rosette-forming lymphocytes. Granulocytes were isolated by sedimentation in 2% methyl cellulose from the erythrocyte-rich pellet formed at the bottom of the Ficoll-Hypaque gradient. The four isolated leukocyte subpopulations were cultured and, at varying intervals, the amyloid A content of the culture medium and of sonicated, 2 x 10(6) cells was determined by radioimmunoassay. Our results indicated a 2-14 times greater amount of amyloid A-related material in the sonicated granulocytes compared with the individuals' serum amyloid A levels. The mononuclear subpopulations showed a low or negligible amyloid A content. The amount of amyloid A antigenic material was further found to increase in cultured granulocytes, reaching a peak value between the 16th and 30th h of culture. The granulocytes of only two out of eight individuals tested released amyloid A antigenically related material into the culture medium. This release was found to be blocked by the presence of colchicine, vincristine, puromycin, or cycloheximide in the culture medium. In contrast, only the presence of puromycin or cycloheximide was shown to significantly inhibit the intracellular increase of amyloid A in the cultured granulocytes. Thus, it appears that among the circulating blood cells, the granulocytes produce amyloid A antigenically related material and could release it under conditions that remain to be further defined.

Superior vena cava obstruction developed a few hours after the administration of chemotherapy for small-cell lung carcinoma. The syndrome responded rapidly to dexamethasone. Although the mechanisms of the appearance and resolution of the superior vena cava obstruction in this patient remain hypothetic, there is an important therapeutic implication.