High incidence of glucose-6-phosphate dehydrogenase deficiency in Croatian island isolate: example from Vis island, Croatia

Aim

To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the population of the town of Komiža on the island of Vis, which has previously been reported as a place with several cases of favism.

Methods

We screened 302 randomly selected men, using the fluorescent spot test. Fluorescence readings were performed at the beginning and 5, 10, and 20 minutes after incubation, and were classified into three groups: bright fluorescence, weak fluorescence, and no fluorescence. All men found to be G6PD deficient were tested with a quantitative spectrophotometric UV method.

Results

Of the 302 tested blood samples, 36 (11.9%) samples showed weak fluorescence or no fluorescence spots. Spectrophotometric UV test showed that 18 (5.96%) men were G6PD deficient. The prevalence of G6PD deficiency in the population of Komiža is significantly higher (P<0.001) than the prevalence in the whole population of Dalmatia in the south of Croatia (0.75% in men).

Conclusion

On the basis of these findings, we recommend including the newborns from the island of Vis into a screening program for G6PD deficiency. Our results indicate that G6PD deficiency should be determined for all the island isolates in the Mediterranean basin and they warrant further studies.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited disorders, with approximately 400 million people affected worldwide (1,2). More than 140 different mutations of the G6PD gene have been identified (3). Molecular analysis of the inhabitants of the Dalmatian region in the south of Croatia identified the G6PD Cosenza (1376 G→C) as the most frequent mutation, followed by G6PD Mediterranean mutation (563 C→T, ref. (4). All individuals with G6PD Mediterranean mutation had concomitant silent C→T transition at the position 1311, which is often found in Mediterranean basin, but not in Asia (5). Association of the factor V Leiden and G6PD deficiency has been observed in Dalmatian population (6).Glucose-6-phosphate dehydrogenase deficiency is unrecognized in most affected individuals. However, it may have a clinical expression such as acute acquired hemolytic anemia, chronic nonspherocytic hemolytic anemia, favism, and neonatal hyperbilirubinemia (7). Different variants of the enzyme are found in high frequency in African, Mediterranean, and Asian populations (8). Heterozygote advantage against malaria was found to account for the high frequency of distinct alleles in particular populations (9).Komiža is a small town on the isolated island of Vis, in the Adriatic Sea, a part of the Mediterranean basin. Although the prevalence of G6PD deficiency has not previously been determined in Komiža, there were several cases of favism originating from Komiža which were treated in our hospital. Therefore, we hypothesized that there could be a significantly higher incidence of G6PD deficiency than in other parts of Dalmatia.The aim of this study was to determine the prevalence of G6PD deficiency in the population of Komiža and compare it with the prevalence of G6PD deficiency in the whole population of Dalmatia. Being an X-linked genetic condition, the prevalence of G6PD deficiency in any given population is determined by the number of men with the deficiency (10).     

Efficacy of a vancomycin solution to prevent bacteremia associated with an indwelling central venous catheter in neutropenic and non-Neutropenic cancer patients

We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with a tunneled central venous catheter (CVC). Eighty-three patients who had a single lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were recorded, and central and peripheral blood cultures were drawn before beginning antibiotic therapy. Patients participated in follow-up for 16,677 catheter days (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and 61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16 occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia occurred in 14 neutropenic (absolute neutrophil count < 500 × 10⁴/l) episodes (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. 0 HepVan; P = 0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients, supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients. Med. Pediatr. Oncol. 28:196–200 © 1997 Wiley-Liss, Inc.     

Apoptosis and active caspase-3 expression in human granulosa cells

OBJECTIVE: To document the expression of activated forms of caspase-3 in human granulosa cells. DESIGN: Laboratory study. SETTING: In vitro fertilization (IVF) laboratory of the Split University Hospital and laboratory of the Department of Anatomy, Histology, and Embryology. PATIENT(S): Ovarian tissues were obtained from women undergoing hysterectomy/ovariectomy for benign conditions and human granulosa cells were obtained from women undergoing oocyte retrieval for IVF. INTERVENTION(S): Immunostaining of tissue sections and cell smears using antibody to active caspase-3 and terminal deoxynucleotidyl transferase (TdT) assay (TUNEL) for detection of internucleosomal DNA fragmentation. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and cellular co-localization of active caspase-3 and TUNEL-positive cells. RESULT(S): In human ovarian tissue, no apoptosis was observed in primordial and primary follicles. Apoptosis in granulosa cells was detected only in atretic antral follicles. Granulosa cells classified as apoptotic on the basis of their morphologic features contained a single condensed nucleus, multiple nuclear fragments, or apoptotic bodies. All apoptotic granulosa cells expressed active caspase-3, but only few contained fragmented DNA detected with the TUNEL method. The expression of active caspase-3 was also demonstrated in human granulosa cells of preovulatory follicles obtained from patients undergoing IVF. CONCLUSION(S): Caspase-3 dependent apoptosis occurs in human granulosa cells and activates when follicles begin to leave the resting pool. After initial formation of the antrum, activation of caspase-3 is a normal physiologic process of the follicle during atresia and luteinization. Higher numbers of granulosa cells positive with caspase-3 than cells positive with TUNEL suggest an earlier activation of caspase-3 compared with the DNA fragmentation detected by TUNEL assay and also a longer detection period of caspase-3 than DNA fragmentation in apoptotic granulosa cells.     

The treatment of advanced renal cell cancer with high-dose oral thalidomide

Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. We have evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with renal carcinoma. 25 patients (all men; median age, 51 years; range 34-76 years) with advanced measurable renal carcinoma, who had either progressed on or were not suitable for immunotherapy, received thalidomide in an escalating schedule up to a maximum dose of 600 mg daily. Treatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed partial responses (9%; 95% CI: 1-29), 7 (32%; 95% CI: 14-55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8-45) had stable disease for between 3 and 6 months. We also measured levels of TNF-alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD > or = 3 months or an objective response, a statistically significant decrease in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11 patients) and neuropathy (> or = grade II, 5 patients). Toxicities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies.     

Painful Peripheral Nerve Injury Decreases Calcium Current in Axotomized Sensory Neurons

Background: Reports of Ca2+ current (ICa) loss after injury to peripheral sensory neurons do not discriminate between axotomized and spared neurons. The spinal nerve ligation model separates axotomized from spared neurons innervating the same site. The authors hypothesized that ICa loss is a result of neuronal injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4 neurons, as well as neurons from rats undergoing skin incision alone.

Methods: After behavioral testing, dissociated neurons from L4 and L5 dorsal root ganglia were studied in both current and voltage patch clamp modes. The biophysical consequence of ICa loss on the action potential was confirmed using selective ICa antagonists. Data were grouped into small, medium, and large cells for comparison.

Results: Reduced ICa was predominantly a consequence of axotomy (L5 after spinal nerve ligation) and was most evident in small and medium neurons. ICa losses were associated with action potential prolongation in small and medium cells, whereas the amplitude and duration of after hyperpolarization was reduced in medium and large neurons. Blockade with Ca2+ channel antagonists showed that action potential prolongation and after hyperpolarization diminution were alike, attributable to the loss of ICa.     

Neoadjuvant chemotherapy for breast cancer

Primary or neoadjuvant chemotherapy in early breast cancer offers the chance to use the tumour as an in vivo measure of response, with the additional possibility of downstaging and avoidance of mastectomy. Tumour response to preoperative chemotherapy correlates with the outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases. Randomized studies have shown that preoperative chemotherapy is as effective as postoperative chemotherapy, but there has not been a significant increase in the disease-free survival or overall survival in the groups studied. The overall response rates reported have varied between 60% and 100% with complete clinical responses from 10% to almost 50%, avoiding mastectomy in most cases. Clinical responders have a better prognosis than nonresponders; pathological complete remissions at present offer the best prediction of good long-term outcome, but occur in less than 20% of patients. Biological predictors reflecting changes in apoptosis and/or proliferation may in the future offer the best surrogate markers for long-term outcome, and trials have recently begun in this area.     

Antisperm antibodies and testicular blood flow after inguinal hernia mesh repair

Background

Testicular flow studies after hernia mesh repair mostly showed different outcomes. The reason of infertility in some men after hernia repair is immunological factors. Aim of the study was to investigate the influence of mesh hernia repair on antisperm antibodies production and testicular blood flow and a connection among these parameters.

Materials and methods

A prospective interventional longitudinal cohort study was made on 82 male patients without exclusion criteria who had an inguinal hernia. Patients underwent laparoscopic TAPP or open tension-free hernia repair. Vascular ultrasound and antisperm antibodies were measured in the preoperative and postoperative periods. Main outcome measures were resistive index (RI), peak systolic velocity (PSV) cm/s, and end-diastolic velocity (EDV) cm/s in testicular blood flow measurement and the quantitative value of antisperm antibodies (ASA) in serum (IU/ml).

Results

ASA significantly increased postoperatively only in patients who underwent open tension-free hernia repair (p < 0.001). ASA stayed in normal range in all patients except the one with postoperative complication. Friedman analysis showed significant change of the RI only on intratesticular (p < 0.001) and capsular artery level (0.02) in patients who underwent laparoscopic technique. PSV significantly changed on intratesticular (p < 0.001) and capsular artery level (p = 0.015) in the laparoscopic hernia repair. PSV showed significant change on intratesticular (p < 0.001) and testicular artery levels (p < 0.001) in the open tension-free hernia repair. EDV showed significant change only on testicular artery level (p = 0.032) in the patients who had open tension-free hernia repair. These blood flow parameters significantly increased in the early postoperative period and returned on basal value in the late postoperative period. Parameters of flow did not show any significant correlation with ASA.

Conclusion

Mesh hernia repairs without complication caused only a transitory change in testicular blood flow and no clinical significant autoimmune reaction.     

Parents’ Pain Catastrophizing is Related to Pain Catastrophizing of Their Adult Children

Background  

Parents’ pain behavior is associated with the way their children experience and express pain.