Laparoscopic management of ovarian tumors

BACKGROUND: Laparoscopy can be used with minimal operative morbidity to evaluate adnexal masses. We report our experience with the endoscopic approach to the diagnosis and treatment of ovarian tumors. In particular, we describe 11 patients who incidentally underwent laparoscopy and in whom the ovarian masses were found to be malignant. METHODS: Between September 1994 and September 1996, 292 patients with 316 ovarian tumors were treated laparoscopically in the Department of Obstetrics-Gynaecology, University of Ulm. We assessed vaginal ultrasonography, clinical assessment, the tumor marker CA 12-5, and the intraoperative low-power magnification for their value in predicting the final diagnosis in all laparoscopically treated ovarian tumors. RESULTS: From a total of 292 patients with ovarian tumors, 11 were diagnosed, intraoperatively or after final histologic examination, as having a malignant or borderline ovarian tumor. All applied pre- and intraoperative diagnostic procedures were by themselves too unreliable to exclude early stages of ovarian carcinoma exactly. CONCLUSIONS: On the basis of the present findings, we are tempted to conclude that laparoscopic surgery is justified in the management of ovarian tumors. Even with an accurate preoperative selection of suitable patients for laparoscopic surgery, the presence of an undetected ovarian carcinoma cannot be entirely excluded.     

An assessment of the osteoinductive potential of commercial demineralized freeze-dried bone in the murine thigh muscle implantation model

Early studies have demonstrated that implantation of laboratory preparations of demineralized freeze dried bone (DFDB) into the thigh muscle of mice induces ectopic osteoinduction. However, with the development of commercial preparations of DFDB for clinical use, concerns have been raised as to the osteoinductive properties of such preparations. The aim of this study was to investigate the osteoinductive potential of some commercial preparations of DFDB compared to a newly developed product which incorporates DFDB into a collagen sponge. Commercial preparations of DFDB or the DFDB/collagen sponge were inserted into the thigh muscles of 60 adult Swiss CD-1 mice. At the completion of each experimental period (7, 14, 30, 90 and 180 days), the animals were sacrificed, and the hindquarters of the mice were radiographed. The area where each graft had been placed was then excised, processed for light microscopy, and stained with hematoxylin and eosin or von Kossa's stain. Histological analysis of the DFDB/collagen sponges demonstrated significant remineralization which increased with time. Remineralization of the DFDB/collagen sponges was verified by radiographs which showed a significant increase in radiopacity over time. There was no radiographic evidence of mineralized tissue formation or remineralization in any of the commercial DFDB samples studied. At all time points studied, histological analyses failed to show evidence of bone formation for any of the preparations. The results suggest that commercially available DFDB is not osteoinductive in the murine model and question the use of such materials in clinical periodontics. The results found for the DFDB/collagen sponge indicate a different mechanism of activity from DFDB as evidenced by its rapid remineralization. The role this remineralization process has in osteoinduction is unknown and requires further study.     

Diabetic-like retinopathy: early and late intervention therapies in galactose-fed rats

PURPOSE: To determine whether the diabetic-like thickening of retinal capillary basement membrane (RCBM) that develops in the galactose-fed rat model of diabetic ocular complications could be halted or ameliorated after 4 or 8 months of galactosemia by treatment with ARI-509, a potent new aldose reductase inhibitor (ARI), or by withdrawal of the galactose diet. METHODS: Weanling female Sprague-Dawley rats were randomized into eight groups and fed laboratory chow plus 50% starch, control group (CON); 50% D-galactose, galactose-fed group (GAL); 50% D-galactose with ARI-509 at 25 mg/kg or 10 mg/kg body wt per day, high-dose prevention group (HDP) and low-dose prevention group (LDP), respectively; 50% D-galactose for 4 or 8 months and then intervention by addition of ARI-509 (25 mg/kg body wt per day), 4-month intervention group (4IN) and 8-month intervention group (8IN), respectively; or 50% D-galactose for 4 or 8 months and then intervention by withdrawing galactose and replacing it with the 50% starch diet, 4-month galactose withdrawal group (4GW) and 8-month galactose withdrawal group (8GW), respectively. After 4, 8, 16, and 24 months of the experimental diets, the levels of carbohydrates in tissues and the extent of RCBM thickening in capillaries of the outer plexiform layer were determined in all groups. RESULTS: Retinal polyol was reduced by 95% in all ARI-treated groups and by 100% in the 4GW and 8GW groups after withdrawal of the galactose. The mean RCBM thickness increased rapidly in GAL rats, becoming almost two times greater (189 +/- 9.4 nm) than in CON rats (103 +/- 3.4 nm) by 24 months. Treatment with ARI-509 in high and low doses (HDP, LDP) initiated with the introduction of the galactose diet significantly prevented RCBM thickening at all time points (P < 0.05). In contrast, intervention by withdrawing galactose from the diet or by adding the high dose of ARI-509 had no significant effect (P < 0.05) on RCBM thickening until the 24-month time point (4IN, 166 +/- 10.3 nm; 8IN, 161 +/- 8.2 nm; 4GW, 136 +/- 5.1 nm; 8GW, 163 +/- 9.6 nm). CONCLUSIONS: Both early and late interventions decreased RCBM thickening compared with that in untreated GAL rats. The decreased thickening, however, was not evident until 16 to 20 months after the intervention. Because RCBM thickening is one of the earliest changes in diabetic and galactosemic retinopathy, the findings suggest that RCBM thickening and possibly subsequent retinal lesions are caused by early biochemical alterations induced by the galactose diet that are not readily reversed. The delayed response to therapy is consistent with that observed in the Diabetes Control and Complications Trial. The cumulative evidence indicates that intervention should begin as early after onset of diabetes as possible, and long follow-up periods should be used to evaluate efficacy.     

In vitro disulfide-coupled folding of guanylyl cyclase-activating peptide and its precursor protein

Guanylyl cyclase-activating peptide II (GCAP-II), an endogenous ligand of particulate guanylyl cyclase C (GC-C), is processed from the precursor protein and circulates in human blood. GCAP-II consists of 24 amino acid residues and contains two disulfide bridges. The correct disulfide paring of GCAP-II is an absolute requirement for its biological activity. This study shows that the folding of the peptide from the reduced form yields a peptide with the native disulfide paring as a minor product and with non-native ones as major products, regardless of the presence or absence of reduced and oxidized glutathione. The results suggest that GCAP-II does not possess sufficient information to permit the adoption of the native conformation and to effectively form the correct disulfide pairing and, as a result, that GCAP-II is correctly folded by assistance of a factor(s) such as an intra- or intermolecular chaperone. We studied whether a peptide in the pro-leader sequence of the precursor protein (proGCAP-II) contains sufficient information to facilitate the folding of GCAP-II. For this purpose, we prepared proGCAP-II in Escherichia coli by a recombinant technique and examined the disulfide-coupled folding of proGCAP-II from the reduced form. proGCAP-II was quantitatively recovered with the correctly folded structure from the reduced form both in the presence and in the absence of reduced and oxidized glutathione. The protein contains only disulfide linkages at the same positions as the mature form of proGCAP-II, GCAP-II, and the biologically active isomer of GCAP-II in the molecule. These results provide evidence that the propeptide of proGCAP-II is a critical factor in the formation of the correct disulfide paring in the folding of the protein.     

A conserved mode of head segmentation in arthropods revealed by the expression pattern of Hox genes in a spider

Chelicerates constitute a basic arthropod group with fossil representatives from as early as the Cambrian period. Embryonic development and the subdivision of the segmented body region into a prosoma and an opisthosoma are very similar in all extant chelicerates. The mode of head segmentation, however, has long been controversial. Although all other arthropod groups show a subdivision of the head region into six segments, the chelicerates are thought to have the first antennal segment missing. To examine this problem on a molecular level, we have compared the expression pattern of Hox genes in the spider Cupiennius salei with the pattern known from insects. Surprisingly, we find that the anterior expression borders of the Hox genes are in the same register and the same relative segmental position as in Drosophila. This contradicts the view that the homologue of the first antennal segment is absent in the spider. Instead, our data suggest that the cheliceral segment is homologous to the first antennal segment and the pedipalpal segment is homologous to the second antennal (or intercalary) segment in arthropods. Our finding implies that chelicerates, myriapods, crustaceans, and insects share a single mode of head segmentation, reinforcing the argument for a monophyletic origin of the arthropods.     

Surgical management of patients with persistent or recurrent medullary thyroid cancer

OBJECTIVE: To compare estimates based on vaccination cards, parental recall, and medical records of the percentages of children up-to-date on vaccinations for diphtheria, tetanus, and pertussis; polio; and measles, mumps, and rubella. METHOD: The authors analyzed parent interview and medical records data from the Baltimore Immunization Study for 525 2-year-olds born from August 1988 through March 1989 to mothers living in low-income Census tracts of the city of Baltimore. RESULTS: Only one-third of children had vaccination cards; based on medical records, these children had higher up-to-date coverage at 24 months of age than did children without cards. For individual vaccines, only two-thirds of parents could provide information to calculate coverage rates; however, almost all provided enough information to estimate coverage for the primary series. For each vaccine and the series, parental recall estimates were at least 17 percentage points higher than estimates from medical records. For children without vaccination cards whose parents could not provide coverage information, up-to-date rates based on medical records were consistently lower than for children with cards or with parents who provided coverage information. CONCLUSIONS: Population-based vaccine coverage surveys that rely on vaccination cards or parental recall or both may overestimate vaccination coverage.     

Cephalometric analysis of a Sotho-Tswana group

A cephalometric study was conducted on 50 male and 54 female Sotho-Tswana children 11-16 years of age. The subjects were selected for excellence of occlusion and balance of facial proportions. Various analyses, including Steiner, Wits, and McNamara, were used for the evaluations. The mean measurements were compared with those of other Southern African Black groups and Caucasoids. Our study shows that cephalometric analyses for other groups cannot be used with confidence for the Sotho-Tswana people and our data provides norms for them.     

Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38

Excessive neutrophil activation causes posttraumatic complications, which may be reduced with hypertonic saline (HS) resuscitation. We tested if this is because of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25 mM) suppressed degranulation and superoxide formation in response to fMLP and blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in response to phorbol myristate acetate (PMA). This indicates that HS suppresses neutrophil function by intercepting signal pathways upstream of or apart from PKC. HS activated p38 by itself and enhanced degranulation in response to PKC activation. This enhancement was reduced by inhibition of p38 with SB203580, suggesting that p38 up-regulation participates in HS-induced enhancements of degranulation. HS had similar effects on the degranulation of cells that were previously stimulated with fMLP, but had no effect on its own, suggesting that HS enhancement of degranulation requires another signal. We conclude that depending on other stimuli, HS can suppress neutrophil activation by intercepting multiple receptor signals or augment degranulation by enhancing p38 signaling. In patients HS resuscitation may reduce posttraumatic complications by preventing neutrophil activation via chemotactic factors released during reperfusion.     

Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases

OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.     

Determination of peptidoglycan-associated protein in Escherichia coli NCIB 8545 by capillary zone electrophoresis

An efficient reliable and sensitive capillary zone electrophoresis assay for the six major bacterial peptidoglycan-associated proteins of Escherichia coli NCIB 8545 is described. The method provides the facility to determine quantitatively the effect of antibacterials on bacterial peptidoglycan-associated protein synthesis and thus to further elucidate the mechanism of antibacterial action of such drugs as the antifolates which recently have been shown to adversely affect peptidoglycan synthesis.