Re: "Self-evaluated health and mortality among the elderly in New Haven, Connecticut, and Iowa and Washington Counties, Iowa, 1982-1986".
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Biomedical subjects
Publications and source records attributed to G Kaplan.
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One hundred twenty major general surgical procedures were performed on 88 adult patients harboring the human immunodeficiency virus. Fifty-eight (48%) of the procedures were performed on patients who fulfilled the criteria for acquired immunodeficiency syndrome. The patients were predominantly male (94%). Single risk factors included homosexuality (73% of cases), intravenous drug abuse (8%), and previous blood transfusions (8%). Four patients (5%) had multiple risk factors; risk factors were denied by seven patients (8%). The mean age at surgery was 41.6 years (range, 22 to 67 years). Surgical conditions that rarely affect the population without the human immunodeficiency virus presented diagnostic challenges. Altered physiologic responses to even routine conditions were observed. Thirty-day morbidity rates for emergency (group A) and elective (group B) procedures were 19% and 9%, respectively. This included seven surgical deaths (13%) in group A and one in group B (2%). Patients undergoing 92 of 112 procedures (82%) not associated with surgical mortality were followed up. Patients who were dead at follow-up had mean procedure-survivals of 19 weeks (group A) and 21 weeks (group B) for 33 procedures. Those who remained alive had a mean procedure-survival of 86 weeks for 59 procedures. No single prognosticator could be correlated with outcome, although the combination of hypoalbuminemia with a history of opportunistic infection(s) was associated with short survival. Emergency and elective procedures can be performed in the patient with human immunodeficiency virus/acquired immunodeficiency syndrome with acceptable morbidity and mortality. Procedures are indicated to extend patient life or to improve quality of life.
We have examined the effect of the intradermal administration of IL-2 on the generation of natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity. Peripheral blood mononuclear cells (PBMC) obtained from borderline lepromatous (BL) and lepromatous leprosy (LL) patients and normal volunteers prior to and after IL-2 injection were stimulated in vitro with IL-2 and their cytolytic activities compared against 51Cr labeled target K562 cells, Daudi cells, and monocytes. Before IL-2 administration, PBMC obtained from BL/LL patients and normal volunteers possessed similar levels of NK cell activity indicating that the NK cell activity of the BL/LL patients was intact. LAK cell activity was induced with IL-2 in vitro in both BL/LL patients and in normal volunteers. The level of LAK cell activity in BL/LL patients was, however, suboptimal. A single intradermal dose of 25 micrograms IL-2 had no effect on the phenotype of circulating mononuclear cells in either patients or normal volunteers. However, 6-12 days after IL-2 injection and subsequent restimulation of the PBMC with IL-2 in vitro, cytolytic activity of LAK cells obtained from the BL/LL patients was enhanced while cells from normal volunteers expressed the same high levels of activity as observed before IL-2 injection.
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The intradermal injection of the purified protein derivative of tuberculin into lepromatous leprosy patients leads to a local cell-mediated immune response and to the extensive destruction of Mycobacterium leprae. This local response also occurs after intradermal injection of recombinant human interleukin-2; when administered over an 8-day period interleukin-2 evokes a systemic cell-mediated immune response and a reduction in the bacillary burden.
Isotretinoin and etretinate are synthetic derivatives of vitamin A widely used in the treatment of dermatological diseases, mainly those affecting keratinization. They have numerous side-effects, among which the rheumatic symptoms are not the most common or the most severe. The main skeletal adverse reaction of retinoids is hyperostosis. It mainly occurs with protracted treatments and high dosages, and its incidence may exceed 80% after a few years of administration. Hyperostosis is axial, located in the cervical and thoracic spine, and may be responsible for limitation of movement; in the appendicular bone, enthesopathies occur at the foot, pelvis, hip, and less commonly the shoulder and elbow. They are usually mild and asymptomatic. The radiological appearance is very similar to diffuse idiopathic skeletal hyperostosis. Isotretinoin tends to be responsible for axial involvement, etretinate for peripheral locations. The other skeletal side-effects are uncommon and include periosteal proliferation, calcification of the interosseous membrane of the forearm and diffuse radiological bone hyperlucency. In children, premature epiphyseal closure is very rare. About 20% of patients complain of musculoskeletal pain and arthralgias. A few cases of true arthritis have been reported. Retinoids may be responsible for muscular damage and an abnormality of muscular tone resembling the stiff-man syndrome. Some cases of necrotizing vasculitis and three cases of Wegener's granulomatosis have been observed in patients treated with retinoids. Except for these latter arguable cases, rheumatoid syndromes due to retinoids are rather benign, and should not be an obstacle to the future development of their therapeutic utilization.
As the number of patients infected with the human immunodeficiency virus (HIV) increases and their life-expectancy grows, more patients will present with conditions that require surgical intervention. Laparoscopic procedures provide several specific advantages over traditional (open) procedures in this population. For the patient, the extent of invasiveness is diminished; incisions are limited; healing time and wound complications can be decreased; pulmonary function is optimized; and the patient rapidly returns to regular activity. For the surgical team, risk of exposure to body fluids is minimized. For the general population, the exclusive use of readily available disposable instruments addresses infection control issues. Of 62 procedures performed on HIV-infected patients prior to the availability of laparoscopic surgery in the general surgery department, 27 (43.6%) could have been approached laparoscopically. Two patients with HIV infection are described who recently underwent successful laparoscopic procedures. In one case, this approach was the only option the patient would consent to. More widespread use of the approach should be specifically encouraged in patients with HIV infection.
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Identification of individuals at risk for developing leprosy and their early diagnosis are central to effective disease control. Lack of immunologic response to Mycobacterium leprae among persons exposed to the infectious agent may be predictive of susceptibility. M. leprae-induced interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells was used as a measure of immune responsiveness. Household contacts of multibacillary patients likely to be at risk of developing active disease were identified, and a preliminary analysis after 2 years of follow-up is presented. A persistent in vitro negative response to M. leprae was present in 34.6% of the contacts, and a decrease in IFN-gamma production was noted in 52.5%. Five contacts (6.41%) developed leprosy during follow-up and, as predicted, belonged to the group of individuals who were negative or showed reduced levels of IFN-gamma in response to the antigen.
Major immunogenic sites of foot-and-mouth disease virus (FMDV) have been mapped to the C-terminal third of capsid protein VP1; we studied the immunogenicity of a series of TrpE-FMDV fusion proteins containing this region of FMDV strain O1 Campos. Fusion protein TrpE-dCN, which contains a dimer of VP1 amino acid sequences consisting of amino acids 200 to 213 linked by a diproline spacer to amino acids 141 to 158 (200-213 approximately P-P-G approximately 141-158), induced the best response. A single inoculation of guinea-pigs with 100 micrograms TrpE-dCN elicited high levels of neutralizing antibodies and protected all the animals against challenge infection with homologous virus. Although the closely related FMDV strains O1 Campos and O1 Caseros induced high levels of cross-protection, TrpE-dCN-vaccinated guinea-pigs were poorly protected against challenge infection with heterologous FMDV strain O1 Caseros. Nucleotide sequence analysis revealed that amino acid differences at residues 149 and 152 were critical for the induction of cross-protection and that neutralizing epitopes not present in TrpE-dCN are likely to be responsible for conferring a high level of cross-protection between FMDV strains O1 Campos and O1 Caseros.
A line of HeLa cells (SOFIA) was previously isolated that is resistant to poliovirus infection and does not express functional virus binding sites at the cell surface. The expression of the poliovirus receptor (PVR) gene in SOFIA cells was examined to determine the molecular basis for the failure of these cells to express PVRs. Southern blot analysis of genomic DNA revealed that the PVR gene in SOFIA cells did not contain gross alterations. However, PVR transcripts were not detected in Northern (RNA) blot analysis of SOFIA cell RNA. In vitro nuclear run-on analysis showed that transcription of PVR-specific RNA was reduced in SOFIA cells. Treatment of SOFIA cells with 5-azacytidine restored susceptibility to poliovirus infection, which correlated with the appearance of PVRs at the cell surface, as detected with anti-PVR monoclonal antibody D171. PVR RNA was detected in clones derived from 5-azacytidine-treated SOFIA cells. SOFIA cells were converted to poliovirus sensitivity at a rate of 5 to 7%, suggesting that down regulation of PVR expression involved few cellular targets. Resistance of SOFIA cells to poliovirus infection therefore appears to result from down regulation of PVR RNA, leading to lack of PVR expression at the cell surface. Methylation may play a role in regulating the expression of the PVR gene, which is not essential for survival of HeLa cells.
Fourteen cases of vasculitis associated with a neoplasm are reported. The vasculitides were classified as: leukocytolytic vasculitis 7, periarteritis nodosa 4, purpura rheumatica 1, cutaneous granulomatous vasculitis 1, microvasculitis nervosa 1. The neoplasms were diagnosed as: 10 hemopathies (including 4 cases of refractory anemia) and 5 solid tumors (1 patient had 2 tumors). The cutaneous manifestations (purpura, papules, subcutaneous nodules, etc.) and fever were the most common, while joint and neurological involvement were the rarest. The evolution of the vasculitis was usually corticosensitive and independent of the underlying neoplasm. A review of the literature revealed that these vasculitides (primarily leukocytolytic) were frequently associated with dysplastic myelogenous syndromes and hairy cell leukemia, while bronchopulmonary and colonic neoplasms were the most common solid tumors. The mechanisms giving rise to these vasculitides are discussed.
We report an original form of chronic inflammatory arthritis in 14 young adults, mainly females: an oligoarthritis with antinuclear antibodies. A first group of 10 patients, 9 females and one male, over 17 year-old, mean age 25, presented with monoarthritis or oligoarthritis of the knees, and less frequently of the wrist or elbow. Arthritis was chronic, recurrent, not destructive nor incapacitating. Rheumatoid factor was absent, and the only biologic abnormality was positive ANA at a significant rate. No patient was typed for HLA DR5. No other clinical or biological symptom appeared during a mean follow-up period of 5.5 years (6 mo-30 yrs). The patients have been totally free of any ocular symptoms. The benignity of the disease and its good prognosis must be underlined. Another group of 4 adult women had a similar inflammatory disease, which started during childhood: the biological and clinical spectrum was found quite similar in both groups, except for uveitis which occurred only in the later. Most subsets of juvenile arthritis have counterpart in adulthood, except for the pauciarticular subset with AAN. The cases herein described could fill the gap, the only difference with the juvenile onset form being the absence of uveitis. Thus, even if our observations of oligoarthritis with ANA in young women are the equivalent of the pauciarticular form in young girls, ocular involvement remains specific of childhood.
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Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.
To characterize the type of cell expressing natriuretic peptide receptors in the brain and the nature of these receptors, we conducted studies in primary cultured glial and neuronal cells derived from fetal rat diencephalon. The glial predominant cultures (95% of total cells and glial fibrillary acidic protein positive) expressed nearly a 10-fold greater specific binding of the natriuretic peptides to cell surface receptors compared with the neuron-predominant cultures. Scatchard analysis of binding studies with 125I-atrial natriuretic peptide (ANP) and 125I-brain natriuretic peptide (BNP) revealed a single class of receptors with dissimilar affinities (0.25 +/- 0.09 and 0.74 +/- 0.07 nM, respectively, n = 3 experiments p less than 0.01) but similar numbers of binding sites for both peptides (93 and 88 fmol/mg of protein, respectively). Cross-linking of 125I-ANP and BNP to cultured glia followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography identified distinct bands at either approximate Mr 130,000, or 102,000 and 66,000, corresponding to two high molecular weight (B) receptors and one low molecular weight (C) receptor described in other tissues. Different subtypes of astrocytes appeared to express different B receptors. Binding and cross-linking of radiolabeled ANP or BNP were competitively inhibited equally by unlabeled ANP or BNP, indicating that ANP and BNP probably bind the same receptors. The glial cultures functionally expressed a receptor(s) with guanylate cyclase activity; BNP was less potent than ANP in stimulating cGMP at lower concentrations. These results indicate that both high and low molecular weight natriuretic peptide receptors are expressed in astrocyte-predominant cultures from the fetal diencephalon and suggest that glia participate in several actions of ANP which are probably mediated through this area of the brain.
We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy. Patients were treated with either sodium fluoride (n = 15), or sodium monofluorophosphate (n = 3). Oral calcium supplementation was given in 11 patients, and vitamin D in 13. Stress fractures occurred after 17.1 +/- 10.3 months of therapy (range: 5-41 months). Atraumatic sudden pain in a lower limb bone extremity, normal initial roentgenogram, high 99technetium uptake on early bone scan, and a 3 to 4 week delay in linear bone condensation area at the same site were characteristics of stress fracture. The most frequent sites were the tibial metaphysis (n = 13), femoral neck (n = 10), and calcaneus (n = 4). Biochemical data showed increased plasma alkaline phosphatase levels in 11 patients, and mild renal failure in 2. Bone histomorphometry was performed on an iliac crest specimen in 10 patients at the time of the stress fracture. Trabecular bone volume was normal, and formation parameters were increased. Features of osteomalacia were encountered in only 2 patients with decreased renal function. Trabecular resorption was increased, as assessed by the osteoclastic surface (1.01 +/- 1.15% bone surface), and the number of osteoclasts (0.44 +/- 0.49 per mm2 bone section). The clinical course was favorable in all patients who stopped fluoride, although 5 patients who continued the treatment had either completion of femoral neck stress fractures to hip fractures (n = 2), or recurrent stress fractures (n = 2), or both (n = 1). Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients.