Perirenal fat surface area as a risk factor for perioperative difficulties and 30-day postoperative complications in elective colon cancer surgery.

AIM: Visceral obesity is associated with perioperative and postoperative complications in colorectal surgery. We aimed to investigate the association between the perirenal fat surface area (PRF) and postoperative complications. METHOD: Data on 610 patients undergoing curative, elective colon cancer resection between 2006 and 2016 at Stockholm South General Hospital were retrieved from a local quality register. We assessed perioperative and postoperative outcomes using a multinomial regression model adjusted for age, sex, American Society of Anesthesiologists classification and surgical approach (open/laparoscopy) in relation to PRF. RESULTS: PRF could be measured in 605 patients; the median area was 24 cm2 . Patients with PRF ≥ 40 cm2 had longer operation time (median 223 vs 184 min), more intra-operative bleeding (250 vs 125 ml), reoperations (11% vs 6%), surgical complications (27% vs 13%) and nonsurgical infectious complications (16% vs 9%) than patients with PRF < 40 cm2 , but there were no differences in the need for intensive care or duration of hospital stay. The multivariate analyses revealed an increased risk of any complication [OR 1.68 (95% CI 1.1-2.6)], which was even more pronounced for moderate complications [Clavien-Dindo II, OR 2.14 (CI 1.2-2.4]; Clavien-Dindo III, OR 2.35 (CI 1.0-5.5)] in patients with PRF ≥ 40 vs < 40 cm2 . The absolute risk of complications was similar in men and women with PRF ≥ 40 cm2 . CONCLUSION: PRF, an easily measured indirect marker of visceral obesity, was associated with overall and moderate complications in men and women and could serve as a useful tool in the assessment of preoperative risk.

Presenting symptoms of glioma in adults.

OBJECTIVE: Studies on the presenting symptoms of glioma in adults in the age of readily available MRI imaging are scarce. This study investigates presenting symptoms of glioma and assesses the correlations of the presenting symptoms with patient age and histopathological class of the tumor. MATERIALS AND METHODS: A retrospective review of the medical records of histologically verified glioma patients treated in Turku University Hospital, during 2006-2010, was conducted. The associations between the presenting symptoms and other covariates were assessed individually. RESULTS: One hundred and fifty patients were ascertained. The most common presenting symptoms of glioma were seizure and cognitive disorder. Patients presenting with seizures were younger than patients with cognitive disorders, and the grade of the tumor was also found to significantly correlate with the most common presenting symptoms. Age group and tumor grade were statistically significant factors of cognitive disorder (P = 0.0037 and P = 0.0069) and age group of seizure (P = 0.0065). The associations between the presenting symptoms and the anatomical location, spread into adjacent brain areas, or laterality of the tumor or site of diagnosis were found to be statistically insignificant. Headache was not a common presenting symptom in glioma patients. CONCLUSIONS: The main presenting symptoms of glioma in adults in the MRI age still are seizures and cognitive disorder. Patient age and tumor grade correlate positively with the incidence of cognitive disorder and patient age negatively with incidence of seizure as a presenting symptom. Headache is an uncommon manifestation and does not appear as a sole symptom.

Low salivary IgA activity to cell-surface antigens of mutans streptococci related to HLA-DRB1*04.

BACKGROUND/AIMS: Mutans streptococci are found in almost all individuals, though there are large differences in colonization levels between individuals. These differences are not readily explained, though several factors are believed to influence the colonization. One factor is the immune response to mutans streptococci, mainly provided by salivary immunoglobulin A (IgA). In a previous study, differences in salivary IgA reactions to oral streptococci were observed between human leukocyte antigen (HLA)-DR4-positive and DR4-negative individuals. A lower salivary IgA activity to Streptococcus mutans in particular was most pronounced for two DR4 subgroups, DRB1*0401 and *0404. The main purpose of this study was to further investigate, in a larger study group, the salivary IgA activity to antigens of three oral streptococci in relation to different HLA-DRB1*04 alleles. METHODS: Stimulated saliva was collected from 58 HLA-DRB1*04-positive individuals. Whole cell antigen extracts from S. mutans, Streptococcus sobrinus and Streptococcus parasanguis and the streptococcal antigen (SA) I/II were separated in SDS-PAGE, transblotted and detected with diluted saliva (Western blot), and analyzed in a computer program. All distinct immunoblot bands over 100 kDa were recorded and compared in relation to DRB1*04. RESULTS: The immunoblots revealed lower salivary IgA reactions to S. mutans, S. sobrinus and SA I/II, but not to S. parasanguis, for the DRB1*0401- and *0404-positive individuals compared to other DRB1*04 types. For the *0401 subgroup there was a significant association with a lower IgA response to S. mutans. CONCLUSION: The results confirm earlier observations and may also support previous demonstrated association between colonization by mutans streptococci and the serologically defined HLA-DR4.

Characterization of the expression and function of N-methyl-D-aspartate receptor in keratinocytes.

The N-methyl-D-aspartate (NMDA) receptor is expressed on neural tissue where it gates calcium ion entry upon stimulation. Using immunohistochemistry, it has been demonstrated in this study that the NMDAR1 receptor is also expressed on keratinocytes (KCs) in normal human skin and inflamed psoriatic skin in vivo. Furthermore, the NMDA receptor was functional as demonstrated by the ability of this receptor to trigger Ca++ influx in KCs. Incubation of cultured, human KCs with MK-801 decreases the cell growth and induces an increase in apoptosis. These findings demonstrate that the KC expression of NMDA receptor is a mechanism through which the influx of Ca++ into the cell can be regulated and suggest that the expression of this receptor may play a role in the regulation of KC growth and differentiation.

Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.

Reactive oxygen species (ROS) are known mediators of intracellular signaling cascades. Excessive production of ROS may, however, lead to oxidative stress, loss of cell function, and ultimately apoptosis or necrosis. A balance between oxidant and antioxidant intracellular systems is hence vital for cell function, regulation, and adaptation to diverse growth conditions. Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. In mammals, extracellular forms of Trx also have cytokine-like effects. Mammalian TrxR has a highly reactive active site selenocysteine residue resulting in a profound reductive capacity, reducing several substrates in addition to Trx. Due to the reactivity of TrxR, the enzyme is inhibited by many clinically used electrophilic compounds including nitrosoureas, aurothioglucose, platinum compounds, and retinoic acid derivatives. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In this review, we focus on the reactions of the Trx system with ROS molecules and different cellular antioxidant enzymes. We summarize the TrxR-catalyzed regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-containing substances, lipoic acid, and ubiquinone (Q10). We also discuss the general cellular effects of TrxR inhibition. Dinitrohalobenzenes constitute a unique class of immunostimulatory TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in view of their reactions with the Trx system.

Centrosome-dependent exit of cytokinesis in animal cells.

As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is essential to mitotic fidelity, and its inheritance could be critical to understanding cell transformation. Investigating the behavior of the centrosome in living mitotic cells, we documented a transient and remarkable postanaphase repositioning of this organelle, which apparently controls the release of central microtubules from the midbody and the completion of cell division. We also observed that the absence of the centrosome leads to defects in cytokinesis. Together with recent results in yeasts, our data point to a conserved centrosome-dependent pathway that integrates spatial controls into the decision of completing cell division, which requires the repositioning of the centrosome organelle.

Mammalian thioredoxin reductase is irreversibly inhibited by dinitrohalobenzenes by alkylation of both the redox active selenocysteine and its neighboring cysteine residue.

The immunostimulatory dinitrohalobenzene compound 1-chloro-2, 4-dinitrobenzene (DNCB) irreversibly inhibits mammalian thioredoxin reductase (TrxR) in the presence of NADPH, inducing an NADPH oxidase activity in the modified enzyme (Arnér, E. S. J., Björnstedt, M., and Holmgren, A. (1995) J. Biol. Chem. 270, 3479-3482). Here we have further analyzed the reactivity with the enzyme of DNCB and analogues with varying immunomodulatory properties. We have also identified the reactive residues in bovine thioredoxin reductase, recently discovered to be a selenoprotein. We found that 4-vinylpyridine competed with DNCB for inactivation of TrxR, with DNCB being about 10 times more efficient, and only alkylation with DNCB but not with 4-vinylpyridine induced an NADPH oxidase activity. A number of nonsensitizing DNCB analogues neither inactivated the enzyme nor induced any NADPH oxidase activity. The NADPH oxidase activity of TrxR induced by dinitrohalobenzenes generated superoxide, as detected by reaction with epinephrine (the adrenochrome method). Addition of superoxide dismutase quenched this reaction and also stimulated the NADPH oxidase activity. By peptide analysis using mass spectrometry and Edman degradation, both the cysteine and the selenocysteine in the conserved carboxyl-terminal sequence Gly-Cys-Sec-Gly (where Sec indicates selenocysteine) were determined to be dinitrophenyl-alkylated upon incubation of native TrxR with NADPH and DNCB. A model for the interaction between TrxR and dinitrohalobenzenes is proposed, involving a functional FAD in the alkylated TrxR generating an anion nitroradical in a dinitrophenyl group, which in turn reacts with oxygen to generate superoxide. Production of reactive oxygen species and inhibited reduction of thioredoxin by the modified thioredoxin reductase after reaction with dinitrohalobenzenes may play a major role in the inflammatory reactions provoked by these compounds.

Selective regulation of T-cell development and function by calcitonin gene-related peptide in thymus and spleen. An example of differential regional regulation of immunity by the neuroendocrine system.

In the course of our studies, we have shown the presence of calcitonin gene related peptide (CGRP) by immunocytochemistry in cell bodies and nerve fibers of the murine thymus and in a sparse innervation of the spleen. Receptors for CGRP have been characterized within these glands, and their activation by physiological levels of CGRP was found to suppress Con A-stimulated proliferation of thymocytes and splenic T cells as well as antigen-specific T-cell proliferation. This suppression is blocked by the antagonist for CGRP (CGRP 8-37). Within the thymus cultures, the antagonist CGRP (8-37) alone enhanced proliferation of thymocytes during Con A stimulation, most likely by inhibiting the endogenous release of CGRP into the culture medium by resident thymocytes. Some of the CGRP-induced suppression of mitogenic stimulation of thymocytes, but not of splenocytes, was due to apoptosis. The antagonist, CGRP(8-37), did not block apoptosis caused by Con A or CGRP but rather enhanced it. Flow cytometric analysis of CGRP-treated cultures using antibodies to cluster determinates (CD) showed that the majority of thymocytes undergoing apoptosis induced by CGRP were of the CD4/CD8 double-positive type. These data indicate that apoptosis in the thymocytes is mediated by a CGRP receptor not sensitive to the antagonist CGRP(8-37). Because proliferation of thymocytes and splenocytes induced by Con A is blocked by this antagonist and splenocytes are refractory to CGRP induced apoptosis, CGRP appears to mediate at least two separate functions on subpopulations of thymocytes and T cells via two different CGRP receptors within the gland. These effects of a neuropeptide exemplify the phenomenon of differential regional regulation of immunity by the autonomic and neuroendocrine systems.

Effect of vacuolar proton ATPase on pHi, Ca2+, and apoptosis in neonatal cardiomyocytes during metabolic inhibition/recovery.

Recently, we found that vacuolar proton ATPase (VPATPase) operates in cardiomyocytes as a complementary proton-extruding mechanism. Its activity was increased by preconditioning with resultant attenuation of intracellular acidification during ischemia. In this study, we examined whether VPATPase-mediated proton efflux during metabolic inhibition/recovery may spare Na+ overload via Na+-H+ exchange, attenuate Na+-Ca2+ exchange, and decrease apoptosis. Neonatal rat cardiomyocytes were subjected to 2- to 3-hour metabolic inhibition with cyanide and 2-deoxyglucose and 24-hour recovery. The effect of VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i was studied by flow cytometry with propidium iodide, seminaphthorhodafluor (SNARF)-1-AM, and indo-1-AM staining, respectively. VPATPase inhibition increased the amount of apoptosis measured after 24 hours of recovery and abrogated the protective effect of inhibition of Na+-H+ exchange by (5-N-ethyl-N-isopropyl)amiloride (EIPA). Dual blockade of VPATPase and Na+-H+ exchange was additive in effect with EIPA on pHi during metabolic inhibition/recovery and recovery from the acid challenge with sodium propionate. VPATPase blockade increased the rate of accumulation of intracellular Ca2+ at the beginning of metabolic inhibition and abrogated the delaying effect of EIPA on intracellular Ca2+ accumulation. These results indicate that VPATPase plays an important accessory role in cardiomyocyte protection by reducing acidosis and Na+-H+ exchange-induced Ca2+ overload.

Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase.

Reduction of the antioxidant lipoic acid has been proposed to be catalyzed in vivo by lipoamide dehydrogenase (LipDH) or glutathione reductase (GR). We have found that thioredoxin reductase (TR) from calf thymus, calf liver, human placenta, and rat liver efficiently reduced both lipoic acid and lipoamide with Michaelis-Menten type kinetics in NADPH-dependent reactions. In contrast to LipDH, lipoic acid was reduced almost as efficiently as lipoamide. Under equivalent conditions at 20 degrees C, pH 8.0, mammalian TR reduced lipoic acid by NADPH 15 times more efficiently than the corresponding NADH dependent reduction catalyzed by LipDH (297 min-1 for TR vs. 20.3 min-1 for LipDH). Moreover, TR was 2.5 times faster in reducing lipoic acid with NADPH than in catalyzing the reverse reaction (oxidation of dihydrolipoic acid with NADP+). In contrast, LipDH was only 0.048 times as efficient in the forward reaction as compared to the reverse reaction (using NADH and NAD+). We conclude that all or part of the previously described NADPH-dependent lipoamide dehydrogenase (diaphorase) activities in mammalian systems should be attributed to TR. Our results suggest that in mammalian cells a significant part of the therapeutically important reduction of lipoic acid is catalyzed by thioredoxin reductase.

Events in apoptosis. Acidification is downstream of protease activation and BCL-2 protection.

Cytoplasmic acidification is now recognized as a feature of apoptosis in a variety of systems. However, its relation to other events in the process of apoptosis is not yet characterized. In this work, we examined the effect of BCL-2 overexpression on acidification mediated by cycloheximide treatment or Fas ligation in Jurkat T-lymphoblasts. We find that BCL-2 overexpression attenuates cytoplasmic acidification and apoptosis detected by annexin V labeling. Acidification and phosphatidylserine externalization were found to occur concurrently. We also examined the requirement for protease activation for cytoplasmic acidification to occur and found that inhibition of interleukin-1beta converting enzyme/CED-3 family proteases (using carbobenzoxy-Val-Ala-Asp-fluoromethylketone, an inhibitor of these proteases) prevents acidification and apoptosis mediated by Fas ligation. These studies suggest that BCL-2 acts at a point upstream of acidification and that protease activation is also upstream of acidification.

Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification.

We have previously shown that in neutrophils deprived of granulocyte colony-stimulating factor, apoptosis is preceded by acidification and that the protection against apoptosis conferred on neutrophils by granulocyte colony-stimulating factor is dependent upon delay of this acidification. To test the hypothesis that acidification could be a general feature of apoptosis, we examined intracellular pH changes in another cell line. Jurkat cells, a T-lymphoblastoid line, were induced to undergo apoptosis with anti-Fas IgM, cycloheximide, or exposure to short-wavelength UV light. We found that acidification occurred in response to treatment with these agents and that acidification preceded DNA fragmentation. Jurkat cells were also found to possess an acid endonuclease that is active below pH 6.8, compatible with a possible role for this enzyme in chromatin digestion during apoptosis. Incubation of the cells with the bases imidazole or chloroquine during treatment with anti-Fas antibody or cycloheximide or after UV exposure decreased apoptosis as assessed by nuclear morphology and DNA content. The alkalinizing effect of imidazole and chloroquine was shown by the demonstration that the percentage of cells with an intracellular pH below 6.8 after treatment with anti-Fas antibody, cycloheximide, or UV was diminished in the presence of base as compared with similarly treated cells incubated in the absence of base. We conclude that acidification is an early event in programmed cell death and may be essential for genome destruction.

Serum levels of interleukin 6, interleukin 8, and C-reactive protein after human allogeneic bone marrow transplantation.

Serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) were measured every second day from day -6 to day +86 in 24 patients undergoing allogeneic (n = 23) and syngeneic (n = 1) bone marrow transplantation (BMT). Endogenous serum levels of IL-6, IL-8, and CRP were further analyzed during complications after BMT, such as fever of unknown origin (FUO), severe infectious complications and acute graft-versus-host disease (GVHD). In addition, CRP levels were measured in 10 patients with interstitial pneumonitis of various origins (CMV, idiopathic). In all 24 patients IL-6 and CRP levels showed a characteristic monophasic pattern. After a slight decrease in the first days after BMT, a significant increase was observed, starting on day +3/+5 (P < 0.05) and reaching peak levels on day +9/+11 (P < 0.01). CRP had a similar pattern, with an increase in serum levels on day +3/+5 and maximum levels one to three days after the IL-6 peak was reached. The magnitude of the peak was related to the development of complications in the further course of BMT and was high in patients with and low in patients without complications. Serum levels of both molecules returned to baseline after day 14 posttransplant. Increased IL-6 and CRP levels were observed in the further course of BMT during severe infections or FUO either on the day of clinical onset (IL-6) or three days later (CRP), but not during acute GVHD grade III/IV. CMV interstitial pneumonitis (CMV-IP) was accompanied by an increase in CRP levels, while no such elevations were observed in patients with idiopathic interstitial pneumonitis (IIP). Elevated IL-8 serum levels occurred during bacterial infections, but to a lesser amount also during GVHD and CMV-IP. In conclusion, a characteristic pattern of IL-6 and CRP was observed after allogeneic BMT and a further increase associated with infectious complications. Since no significant elevations were seen in patients with GVHD, we conclude that both molecules are not involved in the induction of GVHD and might be useful diagnostic tools for the prediction and diagnosis of infectious complications after BMT. In contrast, assessment of IL-8 serum values does not permit clinical complications to be specified.

Circulating serum levels of interleukin 6 and C-reactive protein after liver transplantation.

The study objectives were to investigate serum levels of interleukin-6 and C-reactive protein (CRP) after liver transplantation to correlated measurements with various clinical parameters. Twenty-three patients were studied after orthotopic liver transplantation. Serum IL-6 activity was evaluated by testing its capacity to induce proliferation of the IL-6-dependent hybridoma cell line B9. CRP was assessed by a nephelometric method. Only two of seven patients with acute cellular rejection developed an increase of serum IL-6 and CRP. In contrast to this rejection group, elevated IL-6 levels were observed in 7/9 patients with bacterial infections. Peak values for IL-6 were observed one day and for CRP two days after clinical diagnosis of infection. CMV disease was also associated with markedly increased IL-6 and CRP levels in 5/7 patients. Surprisingly, levels in this condition were approximately in the same range as in bacterial infection. IL-6 and CRP serum levels seen in bacterial infection and CMV disease were significantly higher than those in rejection (P less than 0.001). Serum IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6. Preferential elevations of IL-6 and CRP represent one feature of bacterial and viral infections. Elevation of TNF during rejection as described earlier is only rarely accompanied by increased serum IL-6 levels.

p185neu expression in human lung adenocarcinomas predicts shortened survival.

p185neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185neu expression was associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04) and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.

Evaluation of immunocytochemical detection methods of incorporated bromodeoxyuridine in hybridomas.

Bivariate distributions obtained from nominal acid hydrolysis or thermal treatment methods used in the cell cycle analysis of incorporated bromodeoxyuridine were shown to be unacceptable with hybridomas. Four different cell treatment and staining methods were compared. These methods are acid hydrolysis, thermal denaturation, nuclei extraction with pepsin digestion, and simultaneous pepsin digestion and acid hydrolysis. The nuclei extraction method was determined to be the most appropriate for the immunocytochemical staining of incorporated bromodeoxyuridine in hybridomas. The resulting bivariate distribution provides a clear distinction between labelled and unlabelled cell fractions. The method based on nuclei extraction with pepsin digestion was optimized for a hybridoma line used in this study.

Expression of the neu gene-encoded protein (P185neu) in human non-small cell carcinomas of the lung.

The neu protooncogene is a recently described transforming gene originally isolated from ethylnitrosourea-induced rat neuroblastomas. We have examined the expression of the neu gene in human non-small cell lung carcinomas using immunoprecipitation and immunohistochemistry. The neu protein product (p185neu) was present in eight of 22 non-small cell carcinoma cell lines derived from human lung tumors. Expression of p185neu was found in all histological subtypes of non-small cell carcinomas including large cell carcinomas, squamous cell carcinomas, and adenocarcinomas. Extension of these data to biopsy specimens of human lung tumors demonstrated that normal ciliated bronchial epithelium of the peripheral airways expressed p185neu at low levels. Neoplastic cells in four of 12 adenocarcinomas and three of five squamous cell carcinomas also expressed p185neu at levels higher than the normal ciliated bronchial epithelium. Together these studies indicate that p185neu expression is a common feature of human lung tumors.

High glucose prolongs cell-cycle traversal of cultured human endothelial cells.

There is evidence suggesting that the diabetic state adversely affects replication of certain cell populations. We document that exposure to high ambient glucose (20 mM) induces delay in various phases of the cell cycle of human endothelial cells in primary culture. Cells in S phase were labeled with bromodeoxyuridine (an analogue of thymidine), and the cell-cycle position of the labeled cohort was analyzed by flow cytometry at successive time points. The movement of cells exposed to high glucose for 7-8 days was retarded both in S and G2 phases so that the increase in bromodeoxyuridine-positive cells over 24 h was 1.6-fold, versus 2.0-fold in control cultures. In experiments in which mitotic arrest with vinblastine was used to investigate the movement of cells out of G1 phase without interference from reentering cells, depletion of the G1 compartment was significantly inhibited in cultures grown in high glucose. The effects of chronic high glucose on cell cycle occurred while total protein synthesis was not diminished. Acute exposure to high glucose had no effect on cell-cycle traversal or cell generation time. Cell-cycle abnormalities observed in this study may relate to the DNA damage we have previously observed in endothelial cells exposed to high glucose and, if occurring in vivo, could be of pathogenetic importance for the vascular lesions and teratogenicity of diabetes.

Clubbing and hypertrophic osteoarthropathy.

Acquired clubbing of the digits and hypertrophic osteoarthropathy are closely related disorders of unknown etiology that derive special significance from their frequent association with serious underlying diseases of the thorax or abdomen. Most importantly, clubbing or HOA may provide the first clinical indication of a chronic infection or an intrathoracic neoplasm. However, clubbing is easily overlooked on physical examination, and hypertrophic osteoarthropathy is often mistaken for some other disorder. The diagnosis of clubbing is based on the finding of an increase in the soft tissue at the base of the finger or toenails. Of the several objective criteria that have been proposed for the diagnosis of digital clubbing, the best documented and most practical is an increase in the ratio of the distal phalangeal depth (DPD) to the interphalangeal depth (IDP) of the index finger to 1.0 or greater. Hypertrophic osteoarthropathy is characterized in advance cases by the combination of digital clubbing, periostitis of the long bones, arthritis-like changes in the knees, elbows, ankles, and wrists, and swelling of the soft tissues in the distal extremities. Bone scintigraphy has emerged as the most sensitive test for HOA; in fact, a bone scan may show evidence of periostitis in patients with no other signs, symptoms, or radiographic abnormalities of the disorder. The symptoms of HOA respond to anti-inflammatory agents, and to ablation or cure of the underlying disorder.

Studies in homosexual patients with and without lymphadenopathy. Relationships to the acquired immune deficiency syndrome.

We studied the immunologic function of 19 sexually active homosexual men, ten of whom had persistent lymphadenopathy. Analysis of mononuclear cell populations distinguished homosexuals from heterosexual controls since, as a group, homosexuals had increased percentages of natural killer cells (Leu 7+), decreased helper-inducer T lymphocytes (OKT-4+), increased suppressor/cytotoxic (OKT-8+) T lymphocytes, low OKT-4:OKT-8 ratios, and depressed mitogenic responses. Homosexuals without lymphadenopathy were distinguishable from controls by increased percentages of Ia+ cells, decreased OKT-4+ cells, and decreased OKT-4:OKT-8 ratios. Four had positive findings simultaneously for hepatitis B surface antigen (HBsAg) and surface antibody, and five had positive findings for HBsAg alone. Homosexuals with lymphadenopathy were distinguishable from controls by increased percentages of Leu 7+ cells, increased total lymphocyte numbers per cubic millimeter, decreased percentages of both OKT-4+ and OKT-8+ cells, abnormal OKT-4:OKT-8 ratios, and depressed mitogenic responses. Only histories of larger numbers of sexually acquired diseases, higher numbers of OKT-8+ cells per cubic millimeter, and lower mitogenic responses in homosexuals with lymphadenopathy distinguished this group from homosexuals without lymphadenopathy. Furthermore, none of the nine patients tested in this group was HBsAg positive. We conclude that homosexuals without lymphadenopathy are distinguishable from those with lymphadenopathy by both immunologic and serologic abnormalities.