Mortality among Male and Female Hospitalized Alcoholics in Stockholm 1962–1983

The general and case-specific mortality has been studied in a cohort consisting of 3,910 male and 962 female patients admitted to the Magnus Huss clinic, Karolinska hospital 1962–1981. The clinic is specialized in the care of voluntarily admitted patients with alcohol problems. The cohort has been followed until 20 March 1983. During this period there were 1,141 deaths among the male patients which gives the relative risk of 3.0, compared with the male population in Stockholm. Among the females there were 191 cases of death and the relative risk is 5.2. Among males there was a significant excess mortality due to alcoholism, cirrhosis of the liver, pancreatitis, tuberculosis, pneumonia, alcohol intoxication, suicide, other causes of violent death, ischaemic heart disease, cancer in upper digestive tract, primary hepatic cancer and lung cancer. Causes of death where a significant excess mortality was found among females were alcoholism, alcohol intoxication, cirrhosis of the liver, suicide, other causes of violent death and mammary cancer. The mortality ratios among males were lower for the married patients than among those living single. Among females the ratio was lower for divorced patients. There were no significant variations in the mortality ratios among different social classes, with the exception of females from the highest social class, who showed a lower mortality ratio. The mortality was higher among the patients who entered the clinic during the latter part of the observation period. The ratio was highest the first year after admission but there was a significant excess mortality as long as 20 years after the first treatment period.     

Malignancy: Insulin-like Growth Factor-1 (IGF-1) is a Costimulator of the Expansion of Lineage Committed Cells Derived from Peripheral Blood Mobilized CD34+ Cells in Multiple Myeloma Patients

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34(+) progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte - colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34(+) cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation. After 7 days of cytokine-dependent proliferation the total number of viable cells increased 1.6-8.2 times, and subsets of cells expressing the granulocyte marker CD15, the myelomonocytic marker CD64 and the erythrocyte phenotype CD71(high) /CD64(-) were detected among the in vitro cultured cells. Addition of G-CSF together with SCF + IL-3 + GM-CSF increased the number of CD15(+) and CD64(+) cells, but without altering the number of erythroid cells. IGF-1 caused a dose-dependent increase in the number of CD15(+), CD64(+) and CD71(high) /CD64(-) cells, and this increase was detected when cells were cultured in both SCF + IL-3 + GM-CSF alone and G-CSF + SCF + IL-3 + GM-CSF. A minor subset of CD34(+) cells could still be detected among in vitro cultured cells and the number of CD34(+) cells was not altered by adding G-CSF and/or IGF-1. Morphologically recognizable mature granulocytes or erythroid cells could not be detected for any of the combinations investigated. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from apheresis CD34(+) cells.     

Occurrence of Pustular Psoriasis after Treatment of Crohn Disease with Infliximab

Abstract: We report a case of pustular psoriasis induced by anti‐TNF‐α therapy in a 12‐year‐old boy with inflammatory bowel disease. This is a well‐documented phenomenon but remains a clinical challenge, especially when presenting in the pediatric setting.     

Tubular Apocrine Adenoma: Presentation in the Vaginal Introitus of an Eight‐Year‐Old

Abstract: Tubular apocrine adenoma is a very rare hamartomatous lesion that to our knowledge has never been described in the anogenital region in the pediatric population. A brief report of a tubular apocrine adenoma in the vaginal introitus of an 8‐year‐old.     

Influence of extracellular calcium and nifedipine on α1-and α2-adrenoceptor-mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries

The influence of extracellular Ca²⁺ and nifedipine on contractile responses to 10 μM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly α₂-adrenoceptors), the NA-induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly α₁-adrenoceptors) and CMA (sensitive to both at,- and α₂-adrenoceptor selective antagonists). The tonic component of the NA-induced contraction in the four types of artery was substantially suppressed after only short periods in Ca²⁺-free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K⁺ was more sensitive to Ca²⁺ deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca²⁺, can also release Ca²⁺ from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, α₁-adrenoceptor-mediated contractions in the RCA and RMA seem to depend on both Ca²⁺ influx and intracellular Ca²⁺ release, whereas α₂-adrenoceptor-mediated contractile responses in the CCA appear to rely almost entirely on Ca²⁺ influx. Both the maximum response and the tonic component of the NA-induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA-induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca²⁺-free medium, nifedipine almost abolished the contraction induced by re-addition of Ca²⁺, whereas in the other types of artery, Ca²⁺ re-application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca²⁺ influx and intracellular Ca²⁺ release to the contractile activation, but also in the nifedipine sensitivity of the Ca²⁺ entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of α-adrenoceptor stimulated by NA and to the type of vessel studied.     

Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta

The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears mainly to play a role in degradation of trophoblast cell-associated extracellular matrix, and thus may be of greatest importance during early stages of placentation.     

Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer

Heat shock proteins (HSPs) protect cells against stress‐associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow‐up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence‐free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613–0.823 for intensity and 0.584–0.719 for IRp, but only 0.036–0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.     

IMMUNOREACTIVE TRYPSIN SCREENING FOR CYSTIC FIBROSIS

ABSTRACT. Immunoreactive cationic trypsin (irCT) was measured in 22 cystic fibrosis (CF) and 132 control infants. IrCT was analysed with radioimmunoassay of dried blood samples collected for PKU screening around the 5th day of life and stored on filter paper. The mean ± 1 SD level of irCT for the control infants was 42±19 μg/l. Sixteen of the 22 CF children had an irCT level above 100 μg/l (mean + 3 SD) while 6 had a level at or below this cut-off limit. A specificity of 99%, which gives a sensitivity of 73%, and an approximative noise: signal ratio of 30: 1, suggests that the irCT test may be unsatisfactory as a neonatal screening method for CF.