Assessing and Managing Unintentional Weight Loss: A Global Survey of Geriatrician Practice and Their Use of Ice Cream to Address It.

OBJECTIVES: Unintentional weight loss (UIWL) is common among older adults but lacks standardized methods for its diagnosis and management. With a limited understanding on how geriatricians actually address UIWL, we conducted a survey to examine how they diagnose and manage it, and their opinions regarding the use of ice cream to address it. DESIGN, SETTING, AND PARTICIPANTS: An international descriptive, cross-sectional, online survey conducted over a 16-week period in 2019 involving 1131 geriatricians in clinical practice across 51 countries. MEASUREMENTS: We collected information around respondent demographics, use of screening tools and diagnostic investigations, and pharmacological and non-pharmacological approaches to address UIWL. RESULTS: 89.1% of respondents reported frequently seeing UIWL. The most common methods reportedly used to evaluate UIWL were performing a comprehensive history and physical examination (97.4%) and assessing for cognitive impairment (86.5%). 74.2% noted that they routinely prescribed oral nutritional supplements and 71.6% involved non-medical professional(s) to help manage UIWL. While 50.4% reported recommending ice cream to their patients with UIWL, only 30.6% reported being aware of other colleagues recommending it. Geriatricians in practice for 30+ years were significantly more likely to recommend ice cream (P < 0.05). A thematic analysis of qualitative responses identified that prescribing ice cream tended to align both with patient preferences and socio-economic realities. CONCLUSION: While a majority of geriatricians surveyed routinely prescribe ONS and involve others to manage UIWL, at least half are also recommending ice cream. A key practice amongst experienced geriatricians, the use of ice cream could be better acknowledged as a practical and cost-effective way to address UIWL.

Endometrial lysosomal enzyme activity in ovulatory dysfunctional uterine bleeding, IUCD users and post-partum women.

The aim of this study was to evaluate the role of lysosomal enzymes in excessively heavy menstruation by comparing women with menorrhagia due to dysfunctional bleeding or intrauterine contraceptive device (IUCD) use with those with normal menstrual periods or with amenorrhoea associated with breastfeeding. This was a prospective cohort investigation of the activity of four endometrial lysosomal enzymes in three contrasting groups: (i) women with ovulatory dysfunctional uterine bleeding and users of intrauterine contraceptive devices; (ii) breastfeeding post-partum women in whom there are long periods of amenorrhoea, particularly in the early months post-partum; and (iii) normal cycling women. It was found that the total activity of lysosomal enzymes, particularly acid phosphatase and N-acetyl-beta-D-glucosaminidase, was markedly elevated (P < 0.001) in IUCD-exposed endometrium, and endometrium from women with dysfunctional uterine bleeding when compared with endometrium from women with a history of entirely normal menstrual periods or that in post-partum breastfeeding women. The activity of alpha-L-fucosidase was moderately elevated in IUCD users (P < 0.05) and ovulatory dysfunctional uterine bleeding (P < 0.05), whereas alphaD-mannosidase activity was elevated in ovulatory dysfunctional uterine bleeding (P < 0.05), but decreased in IUCD users (P < 0.01). No significant differences were observed in the lysosomal enzyme activities of breastfeeding post-partum women and normal cycling women. These results show that total endometrial tissue activity of four lysosomal enzymes was substantially increased throughout the cycle in most circumstances in women with two different causes for increased menstrual bleeding. This suggests a contributory role to the increased bleeding.

Endometrial lysosomal enzyme activity in normal cycling endometrium.

The objective of this study was to evaluate the possible role of four lysosomal enzymes in endometrial function and remodelling during the normal menstrual cycle by fluorimetric measurement (acid phosphatase, N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and alpha-D-mannosidase). A prospective study was conducted of 45 endometrial biopsies obtained from women with normal menstrual cycles. Activity of all four enzymes was identified in human endometrium. Activity of acid phosphatase and N-acetyl-beta-D-glucosaminidase was relatively high, whilst that of alpha-L-fucosidase and alpha-D-mannosidase was low. There was no significant change in the activity of any of the four enzymes from the proliferative to the secretory phase of the cycle. This study suggests that the activity of these enzymes remains constant throughout a major portion of the normal cycle.

An extended 10-day course of clomiphene citrate (CC) in women with CC-resistant ovulatory disorders.

OBJECTIVE: To evaluate the effectiveness of extended duration clomiphene citrate (CC) (100 mg for 10 days) as an alternative to complex ovulation induction strategies for women who fail to ovulate despite standard incremental doses of CC of > or = 150 mg for 5 days. DESIGN: Retrospective case series. SETTING: University-based infertility practice. PATIENT(S): Thirty women with CC-resistant World Health Organization group II ovulatory disorders. INTERVENTION(S): At least one cycle of 100 mg CC from days 3 to 12. RESULT(S): Fourteen patients (47%) ovulated during 31 of their 48 cycles (65%). Five women (17%) conceived a total of seven singleton pregnancies, including five term deliveries and two spontaneous abortions. Weight, body mass index, and the presence of hyperandrogenism did not predict responsiveness to the extended duration CC. Side effects were similar to those reported during standard CC treatment. CONCLUSION(S): An extended 10-day course of CC provides a simple, noninvasive, and inexpensive alternative for a subset of women with ovulatory disorders that are refractory to standard CC treatment.

Endometrial morphometry in users of intrauterine contraceptive devices and women with ovulatory dysfunctional uterine bleeding: a comparison with normal endometrium.

Copper-bearing intrauterine contraceptive devices (IUCD) are commonly associated with menorrhagia. They cause certain morphological changes in the endometrium. These have been extensively reported and the mechanisms of menorrhagia have been investigated in a number of studies. By contrast, ovulatory dysfunctional uterine bleeding has not been as widely studied and mechanisms of menorrhagia in these patients are still not well understood. In this study, we examined endometrial morphometry in a group of women using IUCD, a group of women with ovulatory dysfunctional bleeding, and a control group of women with entirely normal cycles. There was increased leukocytic infiltration of the endometrium in both groups of women with menorrhagia compared to control cases. In addition, IUCD use was associated with greater luteal phase glandular epithelial height, supporting the concept of a secretory function defect in glandular epithelium. Possible links are postulated between static morphometric observations and dynamic biochemical changes.

PIP: Researchers conducted endometrial morphometry on 23 women suffering from menorrhagia and ovulatory dysfunctional uterine bleeding, 23 users of a copper releasing IUD, and 45 healthy women (controls) to compare their endometrial histology. Cases and controls were patients at Royal Prince Alfred and King George V Hospitals in Sydney, Australia. The endometria of IUD users had many more plasma cells than normal endometria (median, 0.3/1000 stromal cells vs. 0; p 0.05). 12 biopsies from IUD-exposed endometria had no plasma cells at all. Almost all of the remaining biopsies had less than 2/1000 stromal cells. Endometrial gland epithelial height in IUD-exposed users was much greater than that in normal users (26.9 vs. 20.3 mcm; p 0.01). The difference was exclusively due to a change in the secretory phase (29.4 vs. 20.3 mcm; p 0.01), suggesting that there was a secretory function defect in glandular epithelium. All other parameters were not significantly different between IUD users and normal subjects. Women who suffered from menorrhagia and ovulatory dysfunctional bleeding had many more infiltrating leukocytes in their endometrium than those with a normal endometrium (41.1/1000 vs. 30.1/1000; p 0.05). These leukocytes tended to be lymphocytes. All other parameters were not significantly different between menorrhagia sufferers with ovulatory dysfunctional bleeding and normal subjects. Endometrial morphometry of dysfunctional bleeders and of IUD users was not significantly different. These findings suggest that IUD use and ovulatory dysfunctional bleeding may be associated with static morphometric observations and dynamic biochemical changes.

Reproductive function and contraception in the postpartum period.

The postpartum period is a time of major cellular and hormonal change enabling the return of pelvic organs and the hypothalamic-pituitary-ovarian axis to the nonpregnant state. Breast-feeding modifies this change and maintains the endocrine profile and uterine endometrium in a "static" state. In nonlactating women, menstruation returns on average by day 55 to 60 postpartum and ovulation returns on average by day 40 to 50 postpartum. Breast-feeding prolongs the return of menstruation to some 8 to 15 months postpartum and the first ovulation on average was between 30 to 40 weeks postpartum. However, in breast-feeding women, the return of menstruation and ovulation can be quite variable and is influenced by the pattern of breast-feeding, in particular, the intensity and pattern of suckling. There is concern that breast-feeding, although an effective contraceptive on a wide population scale, is unpredictable for the individual. An overall pregnancy rate of 2 to 10 per cent during lactational amenorrhea has been reported. Barrier methods, intrauterine contraceptive devices, and progestogen-only contraceptives are some of the highly effective and most commonly used additional methods of contraception by lactating women. Other methods of contraception during this period include the use of periodic abstinence and combined oral contraceptives. This paper provides an overview of postpartum reproductive function in relation to breast-feeding and the use of contraception in this unique period.

Developmental pattern of Thy-1 immunoreactivity in the human kidney and the application to pediatric renal neoplasms.

The localization of Thy-1, a surface membrane lipoglycoprotein, was investigated using a monoclonal antibody specific for human Thy-1 (HB-2S-1). The localization of Thy-1 during development was established in a series of five fetal, three childhood, and two adult normal kidneys. In this series, Thy-1 immunolocalization progressed from mesangial and endothelial cell staining in the 16- to 17-week fetuses to similar staining along with staining of the parietal epithelium of the capsule and proximal tubule staining in the 20- to 24-week fetuses. Glomerular mesangial cell and endothelial cell staining was absent by 9 months postnatally when the adult pattern of staining was apparent. The localization of Thy-1 during development was also compared with a series of pediatric renal tumors including 14 Wilms' tumors, 3 congenital mesoblastic nephromas, 1 clear cell sarcoma, and 1 pediatric renal cell carcinoma. Thy-1 staining was demonstrated in epithelial tubules of Wilms' tumors and in the spindle-shaped cells of congenital mesoblastic nephroma correlating with Thy-1 immunoreactivity in the kidney proximal tubule and fetal medullary stroma, respectively. Thy-1 staining was absent in the anaplastic epithelial Wilms' tumor, the renal cell carcinoma, and the clear cell sarcoma. This staining pattern fails to provide evidence that these tumors may arise from the medullary mesenchyme or the differentiated proximal convoluted tubule. These results show that Thy-1 is a renal differentiation marker and is useful in the characterization of tumors of renal development.

Laparoscopic salpingostomy with electrocautery in the management of tubal pregnancy.

From August, 1990 to May, 1991, all cases of tubal pregnancy presenting to King George V Hospital for Mothers and Infants were considered for laparoscopic salpingostomy. This procedure involved opening the affected Fallopian tube with diathermy, removal of ectopic tissue via the laparoscope, achieving haemostasis and leaving the tubal incision to heal by secondary intention. The procedure was undertaken in 35 patients and was successfully performed in 31 patients with an average operating time of 66.4 minutes (+/- 20.1 minutes). Average hospital stay was 2.1 days (+/- 1.3). This paper examines the technique and results of the initial learning curve for laparoscopic salpingostomy and finds that with knowledge of potential hazards and care in surgery, this operation can be safely carried out in a selected group of patients.

Identification of Thy-1 homologue in rabbit brain by immunoblot, immunohistochemistry and DNA/DNA hybridization.

A membrane glycoprotein with an apparent molecular weight of approximately 26,000 reacted on immunoblot with a monoclonal antibody (HB-3S-17) directed toward human Thy-1. At cellular level, HB-3S-17 reacted with both rabbit and human cerebral cortexes in a similar manner as demonstrated by immunohistochemical staining. Screening of a rabbit brain expression cDNA library with HB-3S-17 resulted in the isolation of a clone designated RBT-2A-1. The rabbit cDNA insert of RBT-2A-1 hybridized in Southern blot with an oligonucleotide probe derived from the mouse Thy-1.2 gene. These data strongly indicate the existence of a glycoprotein in rabbit brain which is the counterpart of human and mouse Thy-1.

Detection of Thy-1 on cell surface of human T lymphoid cell lines by a monoclonal antibody.

A mouse IgG2b(kappa) monoclonal antibody (MAb) HB-2S-1 against human brain Thy-1 was secreted by a hybridoma clone after fusion of mouse myeloma cells with spleen cells from a mouse that went through a prolonged immunization procedure before fusion. When tested against isolated human Thy-1 by the enzyme-linked immunosorbent assay (ELISA), MAb HB-2S-1 in culture supernatant showed a titer of over 100,000, and a titer of over 10 million in ascites of a mouse injected with the hybrid clone. By immunoblotting, this antibody was found to bind a doublet of protein bands of approximately 25,000 daltons among all proteins solubilized by deoxycholate (DOC) from membrane of human brain cells. When tested on human lymphoid cell lines by immunofluorescence, MAb HB-2S-1 strongly stained four T lymphoma cell lines, C91-Pl, HUT-102, HUT-78, and C5-MJ; and weakly two leukemia cell lines, MOLT-3 and Jurkat(clone E6-1). It did not stain a third T leukemia cell line, CCRF-CEM; a human B cell line, Raji; a plasmacytoma cell line, HMy2; or a myelomonocytic cell line, HL-60. Peripheral blood lymphocytes from ten normal human adults and the viable T cells isolated from another normal individual were also negative.

Identification and characterization of Thy-1 homologues from bovine thymocytes.

Two forms of Thy-1 homologues of apparent mol. wt of 25,000 (designated BTp25) and 45,000 (designated BTp45) were isolated from bovine thymocyte membrane by solubilization, affinity chromatography with Con A, and preparative SDS-PAGE. Both forms reacted with a rabbit antiserum to murine Thy-1 in an enzyme-linked immunosorbent assay (ELISA). BTp45 is most likely a dimer of BTp25, since the two are indistinguishable in their amino acid compositions. Comparison of amino acid compositions of BTp25 and BTp45 to that of rodent and human Thy-1 by the S delta Q index revealed significant relatedness among these molecules. BTp25 and BTp45 demonstrate more structural homology to rodent Thy-1 than to human Thy-1. Detailed chemical analyses indicate that bovine Thy-1 homologues contain neutral sugars and fatty acids covalently bound to the polypeptide chain; therefore, they are lipoglycoproteins.

Release of Thy-1 from human and murine T-cell lines by a specific phospholipase.

Proteins on the outer surface of cultured human and murine lymphoblastoid T cells were labelled with 125I. The labelled cells were incubated with the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Proteins cleaved from the cell membrane by the enzyme were immunoprecipitated with anti-Thy-1 antibodies, separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and identified by autoradiography. A doublet of Thy-1 bands of approximately 16,000 daltons were detected. The result suggests that: Thy-1 is present on the human and murine T cells which we tested, and Thy-1 is attached to the cell membrane via a phosphatidylinositol domain.

Multiple Ya subunits of glutathione S-transferase detected by monoclonal antibodies.

Monoclonal antibodies to ligandin (YaYa) and glutathione (GSH) S-transferase B (YaYc) were produced by hybridomas derived from the fusion of mouse myeloma cells and spleen cells of mice immunized with the YaYa or YaYc proteins, respectively. Enzyme-linked immunosorbent assay was used to screen for antibody-producing clones. Immunoblotting of the subunits of transferase B, ligandin, and another GSH S-transferase containing Yb subunits showed that the monoclonal antibodies produced by two anti-YaYa subclones recognized the Ya subunits of both ligandin and transferase B, but they did not bind Yc or Yb subunits. It was also revealed that antibodies produced by several anti-YaYc subclones recognized the Yc subunit, but not the Ya subunit of the antigen which was used for the immunization of the mice. However, these monoclonal antibodies did bind the Ya subunit of ligandin. These results indicate that the Ya subunits of GSH S-transferase B and of ligandin do share at least one common determinant. However, these two Ya subunits are structurally distinct as evidenced by their differences in binding by monoclonal anti-YaYc antibodies.

Evaluation of the transcutaneous electrical nerve stimulator for postoperative analgesia following cardiac surgery.

The effectiveness of transcutaneous electrical nerve stimulation (TENS) in postoperative pain relief was assessed in this prospective randomised controlled study of 31 patients during the first 72 hours after cardiac surgery. Fourteen patients were given functioning TENS units, and seventeen patients were given non-functioning units. Postoperative pulmonary function tests, analgesic requirements and the incidence of atelectasis were compared in the two groups. Morphine requirement was significantly reduced on the second postoperative day and peak expiratory flow rates (PEFR) were significantly improved for the first two postoperative days in patients with functioning TENS units. The forced vital capacity (FVC) was significantly larger with functioning TENS units on the second postoperative day, but there were no other significant differences in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) values between the two groups. A questionnaire given to patients assessing their opinions of the effectiveness of the TENS unit for analgesia showed a placebo effect in some patients with non-functioning units. In summary, this study suggests that TENS may be of benefit in postoperative pain relief after cardiac surgery, especially on the second postoperative day.

Antigenic determinant(s) shared by the human Thy 1 and human IgG.

A human T cell differentiation antigen (p25) previously described as being the mouse theta equivalent has been examined for shared antigenic determinants with immunoglobulin. A strong cross-reactivity of an antiserum prepared against p25 antigen was established with human IgG subclasses. This antiserum does not react with human IgM or IgA, nor with primate immunoglobulins. The shared determinants appear to be associated with the disulphide-bonded cysteines in the first and third constant domains of the IgG molecule and the 9-112 disulfide bond of Thy 1.

Cytotoxic effect of anti-idiotype antibody-chlorambucil conjugates against human lymphoblastoid cells.

The secreted IgMs of two human lymphoblastoid cell lines, RPMI-6410 and RPMI-8392, were purified. Antisera against these two IgMs were raised in rabbits and made idiotypically specific to the respective antigens through various absorption procedures. By immunofluorescence and radioimmunoassay techniques, the purified anti-idiotype antibodies were found to react also with the membrane Igs of the respective cell lines, but not with those of other cell lines. The purified anti-idiotype antibodies were then coupled with Chlorambucil to form antibody-drug conjugates, whose effectiveness in the in-vitro killing of target cells was evaluated by a chromium-release cytotoxicity assay. The results showed that these anti-idiotype antibody-Chlorambucil conjugates were specifically cytotoxic to lymphoblastoid cells that bore membrane Igs carrying the respective idiotypic determinant(s). Furthermore, the conjugates were far more effective in causing cytolysis to the target cells than either Chlorambucil or the anti-idiotype antibodies alone.

Three monoclonal immunoglobulins, an IgG2(kappa), an IgM(kappa) and an IgM/A hybrid, in one patient. II. Sharing of common variable regions.

Amino acid sequencing and haemagglutination inhibition studies were performed on three monoclonal immunoglobulins (an IgG2, an IgM and an IgM/A hybrid) isolated from a patient afflicted with a multiple gammopathy. The results demonstrated that all three proteins have shared idiotypic determinant(s). Furthermore, the light chains of all three paraproteins have identical NH2-terminal amino-acid sequences at all positions determined thus far. Similarly, the NH2-terminal amino-acid sequence of the gamma 2 chains is identical to that of the mu chain. The evidence strongly suggests a common ancestral clonal origin for cells which produce these paraproteins and that identical variable region (VH and VL) genes were used by the ESM lymphocyte subclones in the biosynthesis of the respective IgM, IgG, and IgM/A hybrid molecules. The occurrence of a mu/alpha hybrid chain, which shares identical V regions with a mu and a gamma chain, is consistent with the concept that IgM-producing cells can develop directly into cells producing other classes of immunoglobulins via separate pathways during B-cell maturation.