Serum soluble IL-6 receptor concentrations correlate with stages of multiple myeloma defined by serum beta 2-microglobulin and C-reactive protein

Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 52 patients with multiple myeloma (MM) and 24 normal controls, using a commercially available immunoenzymatic assay kit. Patients were staged according to the Bataille et al. myeloma staging system based on the levels of patients' serum beta 2-microglobulin and C-reactive protein. Twenty-one patients were at stage A of disease, 19 at stage B and 12 at stage C at the time of serum collection for sIL-6R determination. Serum sIL-6R concentrations ranged from 15 to 176 ng/ml with a mean of 64.8 +/- 35.9 ng/ml and a median of 58 ng/ml in the entire group of patients studied. These values were significantly higher than those of 34.4 +/- 13.4 ng/ml found in the controls (P < or = 0.001). Patients of stage C had higher sIL-6R levels (94.8 + 41.2 ng/ml) than patients of stage B (67.7 +/- 31.0 ng/ml) (P < 0.01), and markedly higher than patients of stage A (45.0 +/- 23.1 ng/ml) (P < 0.001). Serum levels of sIL-6R in patients with stage A disease did not differ statistically from those of the controls. A linear positive correlation was observed between serum levels of the receptor and the stage of MM (r = 0.539, P < 0.001). These data strongly suggest that serum sIL-6R concentrations correlate with the stages of MM and may be used as an indicator of the activity of the disease.     

The energy cost of walking before and after significant weight loss

The purpose of this study was to determine whether significant weight loss reduced the energy cost of activity more than that expected based on decreased body weight. Standing energy expenditure was measured and subtracted from the total energy cost of walking to determine ambulatory energy expenditure (AEE). The energy cost of walking was determined in 11 obese women at baseline, week 9 [after 8 wk of a 1758-3349 kJ.d-1 diet], and week 22 (after 2 wk of weight stability). AEE accounted for 80% of the energy cost of walking. Body weight was the principal determinant of AEE, but the relationship was not 1:1. Subjects reduced body weight by 13% at week 9 and 21% at week 22. Analyses which controlled for the relationship between AEE and weight at baseline, showed no change in AEE at week 9. By contrast, at week 22, AEE was reduced more than expected based on a lower body weight. These findings suggest that after significant weight loss, reduced-obese persons will expend less energy for the same activity, even after accounting for the decrease in body weight. These data also suggest that weight-based estimates of exercise energy expenditure may be inappropriate after significant weight loss.     

Left ventricular volume reduction for end-stage heart failure: new horizon or false dawn?

The topography of the cricoid area (CA) of the subglottic larynx was studied in serial plastinated sections of 21 normal adult specimens. The cricoid area was seen to contain adipose tissue and blood vessels and was located between the internal perichondrium of the cricoid cartilage and a medial and lateral fiber layer of the conus elasticus. The lateral fiber layer was pierced by numerous blood vessels cranially and ventrally, providing connections of the CA with neighboring laryngeal areas and the anterior extralaryngeal region. Dorsocranially, the CA continued into the adipose tissue surrounding the cricoarytenoid joint and was adjacent to early ossifying regions of the cricoid lamina. Caudally, the CA was occasionally connected to the extralaryngeal area by projections of adipose tissue piercing the cricotracheal ligament. As shown previously, the relationship of the CA with adjacent anatomical regions facilitates certain growth patterns of subglottic cancer.     

Complications of laparoscopic paraesophageal hernia repair

The complications of laparoscopic paraesophageal hernia repair at two institutions were reviewed to determine the rate and type of complications. A total of 76 patients underwent laparoscopic paraesophageal hernia repair between December 1992 and April 1996. Seventy-one of them had fundoplication (6 required a Collis-Nissen procedure). Five patients underwent hernia reduction and gastropexy only. There was one conversion to laparotomy. Traumatic visceral injury occurred in eight patients (11%) (gastric lacerations in 3, esophageal lacerations in 2, and bougie dilator perforations in 3). All lacerations were repaired intraoperatively except for one that was not recognized until postoperative day 2. Vagus nerve injuries occurred in at least three patients. Three delayed perforations occurred in the postoperative period (4%) (2 gastric and 1 esophageal). Two patients had pulmonary complications, two had gastroparesis, and one had fever of unknown origin. Seven patients required reoperation for gastroparesis (n = 2), dysphagia after mesh hiatal closure of the hiatus (n = 1), or recurrent herniation (n = 4). There were two deaths (3%): one from septic complications and one from myocardial infarction. Paraesophageal hernia repair took significantly longer (3.7 hours) than standard fundoplication (2.5 hours) in a concurrent series (P <0.05). Laparoscopic paraesophageal hernia repair is feasible but challenging. The overall complication rate, although significant, is lower than that for nonsurgically managed paraesophageal hernia.     

Autocatalytic processing of heme by lactoperoxidase produces the native protein-bound prosthetic group

The covalently bound prosthetic group of lactoperoxidase (LPO) has been obtained by hydrolysis of the protein and identified as a dihydroxylated heme. A baculovirus expression system has been developed for LPO and used to obtain protein in which the heme is only partially covalently bound. Reaction of the purified heme. apoLPO complex with H2O2 results in both autocatalytic modification of the heme and covalent attachment to the protein. Hydrolytic experiments establish that the autocatalytically incorporated heme is bound normally. Two monohydroxylated heme intermediates have been detected. The peroxidative activity of LPO increases in proportion to the extent of covalently bound heme. The LPO results provide a paradigm for autocatalytic incorporation of heme groups into the mammalian peroxidases, including myeloperoxidase and eosinophil peroxidase, all of which exhibit strong sequence similarity with LPO and have covalently-bound heme groups.     

Cloning and identification of human Sca as a novel inhibitor of osteoclast formation and bone resorption

Increased osteoclast activity is responsible for the enhanced bone destruction in postmenopausal osteoporosis, Paget's disease, bone metastasis, and hypercalcemia of malignancy. However, the number of known inhibitory factors that block osteoclast formation and bone resorption are limited. Therefore, we used an expression-cloning approach to identify novel factors produced by osteoclasts that inhibit osteoclast activity. A candidate clone was identified and isolated from a human osteoclast-like multinucleated cell (MNC) cDNA library, named osteoclast inhibitory peptide-1 (OIP-1), and the cDNA sequence was determined. This sequence matched that of the recently identified human stem cell antigen, was structurally similar to the mouse Ly-6 gene family, and the sequence predicted it was a glycosyl phosphatidyl inositol (GPI)-anchored protein that had a cleavable COOH-terminal peptide. Western blot analysis of conditioned media from 293 cells transfected with the OIP-1 cDNA clone confirmed that OIP-1 was released into the media as a membrane-bound GPI-linked protein. Interestingly, both recombinant OIP-1 expressed in Escherichia coli (which does not have GPI linker) and OIP-1 expressed by mammalian cells significantly reduced osteoclast-like MNC formation induced by 1,25-dihydroxyvitamin D3 or PTH-related protein in mouse and human bone marrow cultures, and inhibited 45Ca release from prelabeled bone in fetal rat organ cultures. In contrast, recombinant OIP-1 did not inhibit the growth of a variety of other cell types. These data indicate that OIP-1 is a novel, specific inhibitor of osteoclast formation and bone resorption.     

Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging

Previous research has indicated that individual foods or beverages are ingested independently and do not produce adjustments to the intake of other constituents in the diet (de Castro, 1993; Wilson, 1991). In order to eliminate time of day as a potential contaminant, the present study investigated the accommodation of foods and beverages into the amount ingested at large evening meals only. Adults (n = 601) were paid to maintain detailed diaries of the timings, quantities and preparation techniques of everything they ingested for seven consecutive days. With the exceptions of soup, beef and chicken, 12 out of 15 types of drinks or foods were found to add to the total calories ingested in evening meals without displacing calories ingested in other forms, while ingestion of non-caloric diet sodas was not associated with differences in intake. The fat and protein, but not carbohydrate, contents of the items correlated with a measure of the satiating properties of the particular food or beverage, namely the correlation between the amount ingested of the particular type and the amounts of other nutrients ingested in the meal. The results confirm that intake at a meal is quite elastic and can be significantly influenced by the presence or absence of particular components of the meal and their constituents.     

Implications of complete fertilization failure after intracytoplasmic sperm injection for subsequent fertilization and reproductive outcome

With the introduction of intracytoplasmic sperm injection (ICSI), couples with severe male factor infertility have achieved fertilization and clinical pregnancy rates comparable to other in-vitro fertilization (IVF) patients. However, failure of fertilization still occurs in some patients despite the utilization of microsurgical sperm injection techniques. How such fertilization failure after ICSI might impact later ICSI treatment(s) is unknown. In this investigation, couples with complete fertilization failure after ICSI treated from August 1993 to August 1996 were identified (index cycle, n = 21). Additionally, fertilization data from any previous or subsequent infertility treatments were evaluated. Seven patients (33%) had at least one IVF treatment before the index cycle, although no deliveries occurred. Of patients with complete fertilization failure in the index cycle, 48% (n = 10) underwent at least one subsequent ICSI cycle which proceeded to oocyte retrieval. The remainder (n = 11) elected to discontinue treatment. Although six subsequent cycles were cancelled due to poor follicular response (< or = 2 mature oocytes), all patients electing to continue treatment eventually achieved a subsequent embryo transfer. The clinical pregnancy rate per transfer was 45.4% for this group; the delivery and ongoing pregnancy rate per transfer was 36.3%. Review of semen parameters, superovulation characteristics or other clinical parameters during the three study cycles (pre-index, index, and post-index) was not prognostic of fertilization success or reproductive outcomes in later treatments. Fertilization failure with ICSI therefore could not be predicted by prior cycle performance, although total immotility of spermatozoa at time of oocyte retrieval, total teratozoospermia, and low oocyte yield were common characteristics of couples experiencing complete fertilization failure with ICSI. These findings suggest that fertilization failure in one ICSI cycle does not preclude successful fertilization and delivery in a later ICSI treatment.     

Evaluation of boys with marked breast development at puberty

OBJECTIVE: The purpose of this study was to investigate the efficiency of second-trimester maternal serum screening for Down's syndrome and open neural tube defects using alpha-fetoprotein and free beta-human chorionic gonadotropin as serum markers. METHODS: 3, 188 women underwent testing between 14th and 22nd week of pregnancy. Of all tested patients, 25.4% were >/=35 years old. A cut-off risk of >/=1:250 for Down's syndrome and MS-AFP >/=2.0 MoM for open neural tube defect were considered screen-positive. RESULTS: The detection rate for Down's syndrome was 77.8% (7/9) with 8.2% screen-positive rate (7.9% false-positive rate). When evaluated separately, in patients younger than 35 and in those >/=35 years old, the screen-positive rates were 3.1 and 23.3%, respectively. A total of 52 (1.6%) were found screen-positive for open neural tube defect; 2 cases of encephalocela and 1 case of gastroschisis were confirmed prenatally. CONCLUSION: The respectable number of cases with trisomy 21 identified in this study confirms that routine mid-trimester screening for Down's syndrome including MS-AFP, free beta-hCG and maternal age is useful in identifying pregnancies at increased risk.