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Biomedical subjects

J L Walker

Publications and source records attributed to J L Walker.

At least 19 recordsLinked to original sources
PubMed2005

Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study.

AIMS: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline. METHODS: A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T(0)) and 4 hours after (T(4)) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T(0). RESULTS: At T(0), mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124-142), with 37/102 (36%) hyponatraemic. At T(4), mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic. CONCLUSIONS: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.

Anthropometry↗
PubMed2005

The re-emerging burden of rickets: a decade of experience from Sydney.

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Child, Preschool↗
PubMed2005

Precocious pubarche is associated with SGA, prematurity, weight gain, and obesity.

BACKGROUND: Perinatal stress is thought to underlie the Barker sequelae of low birth weight, of which precocious pubarche may be a manifestation. AIMS: To explore whether prematurity as well as smallness for gestational age (SGA) predisposes to precocious pubarche, and the potential role of excess weight gain during childhood. METHODS: Retrospective chart review of 89 children (79 girls) with precocious pubarche. RESULTS: Sixty five per cent were overweight/obese at diagnosis, compared with 19-24% of Australian children. Thirty five per cent had a history of SGA and 24% of prematurity. Weight SDS increased from birth to diagnosis in 91% of children. The mean change in weight SDS from birth to diagnosis was greater in those who were SGA (2.8, 95% CI 2.2 to 3.4) versus AGA (1.7, 95% CI 1.3 to 2.2), with no difference in the incidence of overweight/obesity. The latter was lower among children born premature (40% versus 72% term) but was associated with a mean increase in weight of 1.3 SDS during childhood. Nine out of ten girls and boys with precocious pubarche had at least one of the three risk factors studied. CONCLUSIONS: Both prematurity and SGA were associated with precocious pubarche, as was overweight/obesity, irrespective of size or gestation at birth. Excess weight gain in childhood may predispose to precocious pubarche in susceptible individuals.

Chi-Square Distribution↗
PubMed2004

Gender differences in the prevalence of childhood sexual abuse and in the development of pediatric PTSD.

Despite an extensive literature on the links between childhood sexual abuse (CSA) and posttraumatic stress disorder (PTSD), our knowledge on the effects of gender in relation to the risks for sexual victimization and subsequent PTSD is limited. We review current knowledge of gender differences in prevalence of CSA and the role of gender in subsequent development of child and adolescent PTSD with specific attention to rates, phenomenology, biological correlates, and risk factors. Despite the heavy bias toward female representation in studies, the literature supports increased rates of CSA and heightened vulnerability to PTSD in girls, as well as possible gender differences in the biological correlates and psychiatric sequelae of CSA. Further work is needed to explore the mechanisms that underlie these differences.

Adolescent↗
PubMed2002

The intracranial complications of rhinosinusitis: can they be prevented?

OBJECTIVES/HYPOTHESIS: Reference textbooks on the intracranial complications of rhinosinusitis imply that many of the intracranial complications of rhinosinusitis can be prevented. We sought to examine whether or not this is true. STUDY DESIGN: A retrospective case series. METHODS: The study included 47 consecutive patients presenting with intracranial complications secondary to rhinosinusitis between 1992 to 1999 with a mean follow-up of 5 years and 1 month. RESULTS: The most common presenting symptoms of intracranial involvement were an altered mental state, headache, fever, seizure, vomiting, a unilateral weakness or hemiparesis, or a cranial nerve sign. These justify an urgent magnetic resonance imaging or computed tomography scan. The importance of imaging before a lumbar puncture cannot be overemphasized. Of particular note was the finding that 21 patients (45%) presented with a periorbital cellulitis or frontal swelling. Therefore, it does not follow that because a collection of pus presents anteriorly it precludes any intracranial involvement. More than half of our patients (55%) had visited their primary care physician with an upper respiratory tract infection and had been treated appropriately. Once any central symptoms or signs developed, there was little evidence of any significant delay in referral to our unit. Only six patients had a history of nasal disease, three having had recent sinus surgery and three having had nasal polyps. Nine patients had significant long-term morbidity, seven patients had epilepsy, one patient had dysphasia, and one patient had right arm weakness. The single death in our series was associated with a cavernous sinus thrombosis. CONCLUSIONS: The report emphasizes the need for surgeons to be alert to the diagnosis, particularly in patients with a periorbital abscess or frontal swelling. Sinus surgery has a role in obtaining pus for culture, as well as draining the sinus if it is in continuity with an intracranial collection. Intracranial infections secondary to rhinosinusitis occur sporadically and, although it appears that this cannot be prevented, early recognition and treatment are essential to reduce any subsequent morbidity or mortality.

Adolescent↗
PubMed2002

Pneumosinus dilatans of the frontal sinuses: two cases and a discussion of its aetiology.

Pneumosinus dilatans is a rare condition with the dilatation of aerated paranasal sinuses. We present two cases and discuss its aetiology, the radiological classification of enlarged aerated sinuses, and its treatment. One much quoted hypothesis for the cause of this condition has been that it is due to a 'ball valve' effect of mucosal closure at the frontal recess. However, one of our subjects has started, and done, a considerable amount of subaqua diving since presenting with their condition and has had no symptoms on diving, or progression of their frontal swelling. This observation, along with the fact that retained secretions are not seen within the sinuses in this condition, raises doubt about the theory that a one-way valve is responsible.

Adult↗
PubMed2001

Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study.

PURPOSE: A phase II study was conducted to determine the efficacy of paclitaxel and valspodar (PSC 833) in patients with advanced epithelial ovarian cancer. Valspodar, a nonimmunosuppressive cyclosporine D analogue that reverses P-glycoprotein-mediated multidrug resistance, in combination with paclitaxel might be active in paclitaxel-resistant and refractory ovarian cancer. PATIENTS AND METHODS: Patients received valspodar 5 mg/kg orally qid x 12 doses. Paclitaxel (70 mg/m(2) intravenously for 3 hours) was administered on day 2, 2 hours after the fifth or sixth dose of valspodar. This treatment was repeated every 21 days. One blood sample was collected before the sixth dose of valspodar for the first three cycles to evaluate valspodar trough concentration. Tumor tissue was obtained from patients for immunohistochemical staining of P-glycoprotein. RESULTS: Of 60 patients entered, 58 were assessable for response. There were five partial responses (8.6%; 90% confidence interval [CI], 3.8 to 20.0; median duration of response, 5.0 months [range, 1.9 to 10.5 months]). Median progression-free survival was 1.5 months (90% CI, 1.4 to 2.4). Grade 3 or 4 toxicities observed were neutropenia, anemia, nausea and vomiting, peripheral neuropathy, and cerebellar ataxia. The trough concentrations of valspodar were > or = 1,000 ng/mL in all but two of 40 patients in the first cycle. Immunohistochemical staining for P-glycoprotein was positive for one of two responding patients. CONCLUSION: Valspodar in combination with paclitaxel has limited activity in patients with paclitaxel-resistant ovarian carcinoma. An international randomized clinical trial of paclitaxel and carboplatin with or without valspodar as first-line therapy in advanced ovarian cancer is underway.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Analysis of FIGO Stage IIIc endometrial cancer patients.

OBJECTIVE: The aim of this study was to analyze FIGO Stage IIIc endometrial cancer (EC) patients to better define clinicopathologic associations, patterns of failure, and survival. METHODS: Charts were abstracted from EC patients with lymph node metastasis from 1989 to 1998. Data on clinicopathologic variables, adjuvant treatment, site of first recurrence, and survival were collected. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method, and multiple regression analysis was done by the Cox proportional hazards model. RESULTS: From 607 EC patients evaluated, 47 (8%) were identified with FIGO Stage IIIc disease. All 47 underwent hysterectomy and pelvic lymph node (PLN) sampling, and 42/47 had para-aortic lymph node (PALN) sampling. Stage IIIc disease was defined by positive PLN alone in 38%, positive PLN and PALN in 41%, and positive PALN alone in 17%. Twelve of 47 also had positive peritoneal cytology and/or adnexal metastases. Grade III tumors were present in 56% and >50% myometrial invasion in 61%. No association between depth of invasion (DOI) and grade was seen, however. Nearly 1/3 of cases had papillary serous or clear cell histology. Postoperative adjuvant treatment included whole abdominal radiation (36%), pelvic radiation with (19%) and without (17%) extended field, chemotherapy (17%), and oral progestins (11%). The 3-year and 5-year survival estimates for all patients were 77 and 65%, respectively. At a median follow-up of 37 months, 5 patients are alive with disease, and 10 are dead of disease. A distant site of first recurrence was most common (21%), followed by pelvic failure (9%). Only 1 patient has had an abdominal recurrence. Univariate predictors of survival included age, DOI, and extranodal disease, but not grade, histology, or PALN involvement. For the 12 patients with nodal disease and positive cytology and/or adnexa, 3-year survival was 39% versus 93% for those patients without evidence of extranodal disease. In a multivariate analysis only DOI was an independent predictor of survival (P = 0.03). CONCLUSIONS: Once lymph node involvement occurs, the importance of additional extranodal disease increases. Consideration of substaging Stage IIIc patients based on positive adnexa or cytology is supported by the data. The extent which adjuvant treatments contributed to the 77% 3-year survival remains to be defined. The patterns of failure suggest a possible role for combined modalities in future treatments.

Adult↗
PubMed2001

Laparoscopic pelvic and paraaortic lymph node dissection: analysis of the first 100 cases.

OBJECTIVE: The aim of this study was to analyze the first 100 cases of planned laparoscopic pelvic and paraaortic lymph node dissection (LND) done for staging of gynecologic cancers. The goal of the study was to assess prognostic factors for conversion to laparotomy and document complications. METHODS: A retrospective review of patients who had planned laparoscopic bilateral pelvic and bilateral paraaortic LND for staging of their gynecologic cancer was performed. Patients were identified by our institutional database and data were collected by review of their medical records. Data were obtained regarding demographics, stage, histology, length of stay, and procedural information including completion rates, operating room time, estimated blood loss, assistant, lymph node count, and complications. Associations between variables were analyzed using Student t tests, analysis of variance, and chi(2) testing (Excel v7.0). RESULTS: A total of 103 patients were identified from 12/15/95 to 8/28/00. Demographics included mean age of 66.2 (25-92) and mean Quetelet index (QI) of 30.8 (15.9-56.1). A total of 34/103 (33.0%) had > or =1 previous laparotomy. Ninety-five patients had endometrial cancer and 8 had ovarian cancer. Eighty-six of 103 (83.5%) were stage I or II. The length of stay was shorter for those who had laparoscopy than for those who needed conversion to laparotomy (2.8 vs 5.6 days, P < 0.0001). Laparoscopy was completed in 73/103 (70.9%) of the cases. Completion rates were 62/76 (81.6%) with QI < 35 vs 11/27 (40.7%) with QI > or = 35, P < 0.001. Significantly more patients had their laparoscopy completed when an attending gynecologic oncologist was the first assistant compared to a fellow or a community obstetrician/gynecologist (92.9%, 69.0%, 64.5%, P < 0.0001). The top three reasons for conversion to laparotomy were obesity, 12/30 (29.1%), adhesions, 5/30 (16.7%), and intraperitoneal disease, 5/30 (16.7%). Pelvic, common iliac, and paraaortic lymph node counts did not differ when compared to those of patients who had conversion to laparotomy (18.1, 5.1, 6.8 vs 17.3, 5.7, 6.8, P = ns). Complications included 2 urinary tract injuries, 2 pulmonary embolisms, and 6 wound infections (all in the laparotomy group). Two deaths occurred, 1 due to a vascular injury on initial trocar insertion and 1 due to a pulmonary embolism after a laparotomy for bowel herniation through a trocar incision. CONCLUSION: Laparoscopic bilateral pelvic and paraaortic LND can be completed successfully in 70.9% of patients. Age, obesity, previous surgery, and the need to perform this procedure in the community were not contraindications. Advantages include a shorter hospital stay, similar nodal counts, and acceptable complications.

Adult↗
PubMed2001

Surgical management of early-stage endometrial cancer in the elderly: is laparoscopy feasible?

OBJECTIVE: To give insight into the utility of laparoscopic staging of endometrial cancer in the elderly population by reviewing the surgical management of clinically stage I endometrial cancer patients. METHODS: A retrospective analysis evaluating patients that were > or =65 years old and had planned laparoscopic staging, traditional staging via a laparotomy, or a transvaginal hysterectomy as management of their early endometrial cancer. The laparoscopic group had complete staging with bilateral pelvic and paraaortic lymph node dissections and was compared to the group who had staging performed via laparotomy. Patients were identified by our institution's database and data were collected by review of their medical records. Data were collected on demographics, pathology, and procedural information including completion rates, operating room (OR) time, estimated blood loss (EBL), transfusions, lymph node count, complications, and length of stay. Associations between variables were analyzed by Student's t tests and chi(2) testing using Excel v. 9.0. RESULTS: From February 25, 1994, through December 21, 2000, 125 elderly patients were identified. Sixty-seven patients had planned laparoscopic staging (Group 1), 45 patients had staging via planned laparotomy (Group 2), and 13 patients had a transvaginal hysterectomy (Group 3). Group 1 and Group 2 were compared regarding surgical and postoperative data. Age was not different between these groups (75.9 vs 74.7 years, P = NS). Quetelet index was also similar (29.4 vs 29.9, P = NS) 32.8% of Group 1 had > or =1 previous laparotomy compared to 51.1% in Group 2 (P = NS). In Group 1, 53/67 (79.1%) had stage I or II disease compared to 29/45 (64.4%) in Group 2 (P = NS). Laparoscopy was completed in 52/67 (77.6%) attempted procedures. The reasons for conversion to laparotomy were obesity 7/67 (10.4%), bleeding 4/67 (6.0%), intraperitoneal cancer 3/67 (4.5%), and adhesions 1/67 (1.5%). OR time was significantly longer in successful Group 1 patients compared to Group 2 patients (236 vs 148 min, p = 0.0001). EBL was similar between these groups (298 vs 336 ml, P = NS). Ten of 52 (19.2%) of successful Group 1 patients received a blood transfusion compared to 1/45 (2.2%) of Group 2 patients (P < 0.0001). Pelvic, common iliac, and paraaortic lymph node counts were similar between successful Group 1 patients and those in Group 2 combined with those that received a laparotomy in Group 1 (17.8, 5.2, 6.6 vs 19.1, 5.1, 5.2, P = NS). Length of stay (LOS) was significantly shorter in Group 1 versus Group 2 (3.0 vs 5.8 days, P < 0.0001). There were less fevers (6.0 vs 15.6%, P = 0.01), less postoperative ileus's (0 vs 15.6%, P < 0.001), and less wound complications (6.0 vs 26.7%, P = 0.002) in Group 1 compared to Group 2. Group 3 average age was 77.5 years. Concurrent medical comorbidities were the main reason for the transvaginal approach. OR time averaged 104.5 min. The average length of stay was 2.1 days with no procedural or postoperative complications. CONCLUSIONS: The favorable results from this retrospective study refute the bias that age is a relative contraindication to laparoscopic surgery. Laparoscopic staging was associated with an increased OR time and an increased rate of transfusion but equivalent blood loss and lymph node counts. Possible advantages are decreased length of stay, less postoperative ileus, and less infections complications. Transvaginal hysterectomy still remains a proven option for women with serious comorbid medical problems with short OR times, minimal complications, and short lengths of stay.

Aged↗
PubMed2001

Rapid cooling techniques in joggers experiencing heat strain.

This study examined subjects that exercised on three occasions in a heated environment (WBGT = 39 degrees C] until they experienced heat strain. Since morbidity and mortality due to heat injury increase with the duration of elevated core temperature, it is important that techniques to lower core temperature be evaluated. Following three exercise sessions, subjects underwent each of three core cooling treatments in random order: 1) Torso immersion in cool water, 2) Hands and feet immersion in cool water, and 3) Sit-in-shade with a 1.5mph breeze provided. Subjects (n=5) consistently reached peak rectal temperatures of 38.8 (+/-0.1) degrees C following each exercise bout in the heated environment. Torso immersion produced a significantly (p<0.05) greater rate of decline in rectal temperature (0.25+/-0.10 degrees C/min) than the hands and feet immersion technique (0.16+/-0.05 degrees C/min) and the sit in the shade technique (0.11+/-0.04 degrees C/min). After only 10 minutes of cooling, the differences among cooling techniques were evident. Similar trends were observed for mean heart rate readings, albeit not significant (p>0.05). It was concluded that rectal temperatures can be reduced rapidly through the use of a cool water torso-immersion technique.

Abdomen↗
PubMed2001

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment.

OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.

Absorptiometry, Photon↗
PubMed2000

A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study.

BACKGROUND: Some endometrial cancers are hormonally dependent. A principal source of circulating estrogen is conversion of adrenal androstenedione by aromatase. Anastrozole (Arimidex) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer. This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma. METHODS: Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease, a GOG (Zubrod) performance status of < or = 2, no more than one prior hormonal therapy regimen, and no prior chemotherapy were eligible. Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days. RESULTS: Twenty-three patients were entered on this trial. On central pathology review, 9 of them had grade 2 and 14 had grade 3 tumors. One to 24 courses (median: 1) of therapy were administered. Two partial responses were noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short-term stable disease. With the exception of 1 case of venous thrombosis, the toxicity profile was mild. Median durations of progression-free survival and overall survival are 1 and 6 months, respectively. CONCLUSIONS: Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer.

Administration, Oral↗
PubMed2000

True hermaphroditism.

OBJECTIVE: True hermaphroditism is a rare cause of atypical genitalia which presents significant diagnostic and management challenges. We present the clinical and laboratory findings and management of four patients with true hermaphroditism. METHODOLOGY: Case studies from a teaching hospital and literature review. RESULTS: All four patients had atypical genitalia identified at birth. All had a palpable gonad, only one of which was palpable at birth. Three patients were 46XX (SRY -ve) and one 46XY (SRY +ve). Three patients were raised as females (two 46XX and one 46XY) and one as a male. All four patients were found to have an ovotestis present. CONCLUSIONS: The management of true hermaphroditism is controversial and requires a multidisciplinary approach. It has many implications for both the parent and child. We discuss the issues involved for the patients and their parents.

Disorders of Sex Development↗
PubMed2000

Dietary carbohydrate, muscle glycogen content, and endurance performance in well-trained women.

This study examined the ability of well-trained eumenorrheic women to increase muscle glycogen content and endurance performance in response to a high-carbohydrate diet (HCD; approximately 78% carbohydrate) compared with a moderate-carbohydrate diet (MD; approximately 48% carbohydrate) when tested during the luteal phase of the menstrual cycle. Six women cycled to exhaustion at approximately 80% maximal oxygen uptake (VO(2 max)) after each of the randomly assigned diet and exercise-tapering regimens. A biopsy was taken from the vastus lateralis before and after exercise in each trial. Preexercise muscle glycogen content was high after the MD (625.2 +/- 50.1 mmol/kg dry muscle) and 13% greater after the HCD (709.0 +/- 44.8 mmol/kg dry muscle). Postexercise muscle glycogen was low after both trials (MD, 91.4 +/- 34.5; HCD, 80.3 +/- 19.5 mmol/kg dry muscle), and net glycogen utilization during exercise was greater after the HCD. The subjects also cycled longer at approximately 80% VO(2 max) after the HCD vs. MD (115:31 +/- 10:47 vs. 106:35 +/- 8:36 min:s, respectively). In conclusion, aerobically trained women increased muscle glycogen content in response to a high-dietary carbohydrate intake during the luteal phase of the menstrual cycle, but the magnitude was smaller than previously observed in men. The increase in muscle glycogen, and possibly liver glycogen, after the HCD was associated with increased cycling performance to volitional exhaustion at approximately 80% VO(2 max).

Adult↗
PubMed1999

alpha6 Integrin is regulated with lens cell differentiation by linkage to the cytoskeleton and isoform switching.

The developing chicken embryo lens provides a unique model for examining the relationship between alpha6 integrin expression and cell differentiation, since multiple stages of differentiation are expressed concurrently at one stage of development. We demonstrate that alpha6 integrin is likely to mediate the inductive effects of laminin on lens differentiation as well as to function in a matrix-independent manner along the cell-cell interfaces of the differentiating cortical lens fiber cells. Both alpha6 isoform expression and its linkage to the cytoskeleton were regulated in a differentiation-specific manner. The association of alpha6 integrin with the Triton-insoluble cytoskeleton increased as the lens cells differentiated, reaching its highest levels in the cortical fiber region where the lens fiber cells are formed. In this region of the lens alpha6 integrin was uniquely localized along the cell-cell borders of the differentiating fiber cells, similar to beta1. alpha6beta4, the primary transmembrane protein of hemidesmosomes, is also expressed in the lens, but in the absence of hemidesmosomes. Differential expression of alpha6A and alpha6B isoforms with lens cell differentiation was seen at both the mRNA and the protein levels. RT-PCR studies demonstrated that alpha6B was the predominant isoform expressed both early in development, embryonic day 4, and in the epithelial regions of the day 10 embryonic lens. Isoform switching, with alpha6A now the predominant isoform, occurred in the fiber cell zones. Immunoprecipitation studies showed that alpha6B, which is characteristic of undifferentiated cells, was expressed by the lens epithelial cells but was dramatically reduced in the lens fiber zones. Expression of alpha6B began to drop as the cells initiated their differentiation and then dropped precipitously in the cortical fiber zone. In contrast, expression of the alpha6A isoform remained high until the cells became terminally differentiated. alpha6A was the predominant isoform expressed in the cortical fiber region. The down-regulation of alpha6B relative to alpha6A provides a developmental switch in the process of lens fiber cell differentiation.

Animals↗
PubMed1999

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Adult↗