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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

DNA-based presymptomatic diagnosis of Wilson disease.

Investigation using DNA markers in a family with Wilson disease revealed that an apparently normal child of 10 years of age with non-diagnostic copper biochemistry had the disease. The procedure used linked restriction fragment length polymorphic markers. Demonstration of increased liver copper concentration from a liver biopsy confirmed the diagnosis and the child was started on chelation therapy. Two other asymptomatic siblings were shown, using the same techniques, not to have the disease. Similar analysis was carried out on another family with just one index case.

Chromosomes, Human, Pair 13

Radical hysterectomy in the elderly patient: analysis of morbidity.

OBJECTIVE: This study compares the perioperative morbidity and mortality following radical hysterectomy of patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA. STUDY DESIGN: A retrospective analysis of morbidity and mortality for the first 60 postoperative days was conducted. The study population of 45 women greater than 65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women less than 65 years treated similarly. RESULTS: In the elderly group, 31 of 45 and 12 of 15 were American Society of Anesthesologists Physical Status II and III respectively; 68/90 and 19/90 were American Society of Anesthesiologists status I and II in the younger age group (p = 0.001). Transfusions of greater than 2 units were required in 14% of the elderly and 35% of younger patients (p = 0.02). No statistical differences were observed between groups for other parameters examined. CONCLUSION: Age alone should not be a contraindication for radical hysterectomy in the elderly patient with American Society of Anesthesiologists Physical Status I to III.

Age Factors

Hypogastric artery aneurysm masquerading as an ovarian neoplasm.

Hypogastric artery aneurysm in women is rare. The case presented demonstrates how this lesion can easily mimic an ovarian neoplasm. The missed diagnosis can be catastrophic if the surgeon is unfamiliar with the retroperitoneal anatomy and is confronted with arterial hemorrhage. Hypogastric artery aneurysm should be included in the differential diagnosis of a pelvic mass in elderly women with atherosclerotic disease. The report reviews the literature on the presentation, diagnosis, and recommended treatments.

Aged

Analysis of fine-needle aspirates for HPV by PCR may be useful in diagnosis of metastatic gynecologic malignancies.

Human papillomavirus (HPV) DNA has been shown by molecular hybridization studies to persist in both recurrent and metastatic disease in tumors of the female genital tract. We report here the use of the polymerase chain reaction to identify HPV DNA in material from fine-needle aspirates (FNA) of recurrent or metastatic lesions to document the primary malignancy arising in the lower genital tract. Fine-needle aspirates of suspected recurrent or metastatic tumors were obtained from nine patients with carcinoma of the lower genital tract and five patients with malignancies that have not been associated with HPV. DNA was extracted from the FNA and tissue block, when available, and amplified with HPV 6, HPV 16, and HPV 18 specific primers. In eight of the nine tumors from the lower genital tract, HPV DNA was identified in both the primary and metastatic lesions. In every case the HPV genotype was identical. One cervical carcinoma and five non-HPV associated tumors were negative for papillomavirus DNA. This study demonstrates that molecular hybridization techniques can be useful in identifying the source of a metastasis and have the potential to diagnose the presence of metastatic disease by detecting HPV DNA even when the cytologic criteria are equivocal.

Biopsy, Needle

Stimulation of statural growth by recombinant insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron type)

We studied the effects of 9 months of treatment with twice-daily subcutaneous injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose, in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short-term studies had suggested that IGF-I might promote linear growth. Height velocity increased from 6.5 cm/yr (+1.7 SD score) to 11.4 cm/yr (+8.8 SD score). Serum concentrations of IGF-I increased from pretreatment values of 9 +/- 2 micrograms/L to a peak of 347 +/- 26 micrograms/L after 2 hours. Serum concentrations of IGF-II were unchanged. Basal but not stimulated growth hormone concentrations were decreased. During the first 12 days of treatment, serum concentrations and the 24-hour urinary excretion of urea nitrogen were decreased by 28% and 10%, respectively (p < 0.05), there was a 2.4-fold increase in urinary excretion of calcium (p < 0.001), and creatinine clearance and urine volume increased by 22% and 55%, respectively (p < 0.02). The changes in serum levels of urea nitrogen and in urinary calcium and creatinine clearance were still evident at 10 weeks. Fasting and postprandial serum glucose concentrations remained normal. We conclude that IGF-I given as twice-daily subcutaneous injections is effective in stimulating statural growth without producing the hypoglycemia and hyperglycemia observed when IGF-I is infused continuously.

Blood Glucose

Tissue-specific developmental regulation of the messenger ribonucleic acids encoding the growth hormone receptor and the growth hormone binding protein in rat fetal and postnatal tissues.

Tissue responsiveness to growth hormone is likely to be regulated by local concentrations and availability of the membrane-bound growth hormone receptor (GHR) and perhaps by the actions of the soluble growth hormone binding protein (GHBP). To determine whether the developmental regulation of the GHR and GHBP might vary among tissues, we have measured the relative abundance of the 4.3-kb GHR and 1.3-kb GHBP mRNA in rat fetal and postnatal liver, kidney, lung, and ileum by Northern hybridization of polyadenylated RNA with a 32P-labeled antisense riboprobe prepared from a rat GHR cDNA. The GHR and GHBP mRNA were both present in the four tissues studied at fetal age 19 d (E19). In postnatal liver, both transcripts increased in abundance 3- to 4-fold after 14 d to mature levels at 42 d (p = 0.0001). Similar changes were seen in postnatal kidney for GHR mRNA abundance; however, GHBP mRNA abundance increased only 2- to 3-fold to mature levels by 28 d (kidney GHR versus GHBP mRNA profile, p = 0.0001). In lung, a 2-fold linear increase in GHR mRNA abundance was observed (p = 0.0019), but the GHBP mRNA did not change (GHR versus GHBP mRNA profile, p = 0.0006). Both transcripts decreased in abundance by 2- to 3-fold from E19 to 42 d in ileum (p less than 0.05). The abundance of both transcripts was three to 10 times greater in 60-d liver than in the other three tissues at 60 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Differential regulation by growth hormone (GH) of insulin-like growth factor I and GH receptor/binding protein gene expression in rat liver.

We have reported that female hypophysectomized (hypox) rats replaced with T4 and cortisone and treated for 7 days with GH injections (4 x 12.5 micrograms/day) had significantly greater growth and increase in serum insulin-like growth factor-I (IGF-I) than did hypox rats continuously infused with GH (50 and 250 micrograms/day), whereas GH binding to liver membranes was increased only by infusion. We now report the effects of hypophysectomy, T4 and cortisone replacement, and the aforementioned continuous vs. intermittent GH treatment on liver IGF-I and GH receptor (GHR)/binding protein (GHBP) gene expression in female rats. Concentrations of IGF-I peptide were measured in acid-extracted sera and liver tissues. Total GH binding to liver membranes was determined in MgCl2-treated homogenates and serum GH binding activity was assessed by gel filtration of serum incubated with 125I-bovine GH. The abundance of messenger RNA (mRNA) transcripts encoding IGF-I, the GHR, and the GHBP was quantified by Northern hybridization analysis of liver poly(A)+ RNA. Hypophysectomy in female animals decreased serum IGF-I and liver IGF-I mRNA concentrations by 95% and 87%, respectively, serum GHBP activity, and total liver GH binding by 50% (P less than 0.001 compared with intact controls), and liver GHR and GHBP mRNA abundance by 30-35% (P less than 0.05 vs. controls). These changes were not reversed by T4 and cortisone treatment. Repeated injections of GH produced a 13-fold increase in liver IGF-I peptide and a 5-fold increase in liver IGF-I mRNA concentrations (vs. saline-treated hypox rats), whereas continuous GH infusions induced only 7-fold and 2-fold increases in IGF-I peptide and mRNA, respectively. Serum GHBP activity was not changed in the GH-injected animals, but rose 2- to 3-fold in the GH-infused rats, an increase similar to that reported for their liver GH binding sites. No major change in liver concentrations of GHR and GHBP mRNAs was seen after repeated GH injections. Differential regulation of the two GHR/GHBP gene products was observed after continuous infusion of GH, with a net 60-70% increase in liver GHBP mRNA abundance contrasting with no apparent change in the GHR mRNA transcript. These results indicate that pulsatile GH administration is more effective than continuous GH infusion in stimulating liver IGF-I gene expression, and this effect is not mediated by an increase in GHR mRNA or protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance

Comparison of clinical versus surgical staging systems in vulvar cancer.

OBJECTIVE: To compare prognostic information from the new surgical staging system of the International Federation of Gynecology and Obstetrics (FIGO) with the old clinical staging system for vulvar cancer. METHODS: One hundred six women with previously untreated squamous cell carcinoma of the vulva who underwent radical vulvectomies and inguinal lymph node dissections at the University of Oklahoma from 1971-1990 were considered eligible for this study. A retrospective chart review was conducted to assign surgical stage. The clinical and pathologic factors analyzed for survival included the clinical and surgical stage of disease, nodal status, tumor size, and lesion location. RESULTS: Overall 5-year survival was 64%. Forty-three patients had inguinal and femoral node metastasis with a 5-year survival of 38%, versus 87% for patients without nodal metastasis (P < .00001). An increased number of positive groin lymph nodes was associated with a poorer prognosis. Thirty-one patients had tumors of 2 cm or less in maximum diameter with no recurrences, versus 52% 5-year survival in the remaining patients (P < .001). Perineal involvement was identified in 24 patients, but did not significantly influence survival. CONCLUSION: Overall, the new classification system revised by FIGO for vulvar cancer staging places patients into more accurate risk categories.

Actuarial Analysis

Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy.

OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph-vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5-year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates.

Actuarial Analysis

Radiation myelitis: a complication of concurrent cisplatin and 5-fluorouracil chemotherapy with extended field radiotherapy for carcinoma of the uterine cervix.

Radiation myelitis is a rare but serious complication of radiation therapy. The total dose of radiation to the spinal cord required to cause myelopathy is greater than 50 Gy when the treatment is administered in 25 or more fractions; however, recent evidence has suggested that the concurrent use of chemotherapy may decrease the tolerance of the spinal cord to radiation. This report describes a case of radiation myelitis in a patient after concomitant fluorouracil/cisplatin chemotherapy and extended field radiotherapy for stage IIA adenosquamous cell carcinoma of the uterine cervix metastatic to the para-aortic lymph nodes.

Adenocarcinoma

Anxiety, inhibition, and conduct disorder in children: I. Relations to social impairment.

Jeffrey A. Gray has proposed a model in which conduct disorder (CD) is viewed as the result of both excessive activity of a behavioral activation system that mediates appetitive and aggressive behavior and deficient activity of a behavioral inhibition system that mediates both anxiety and the inhibition of behavior in the presence of cues signalling impending punishment or frustration. The relation of anxiety to antisocial behavior was examined in 177 clinic-referred boys, aged 7 to 12 years, 68 of whom met DSM-III-R criteria for CD. As predicted by Gray's model, boys with CD and comorbid anxiety disorder were markedly less impaired than boys with CD alone.

Aggression

Photograph as lifeline--facing mortality.

This paper focuses on the use of one photograph helping a terminally ill patient confront the significant issues of her life including her own mortality. In confronting issues of mortality, it is essential to face the issues of life itself concurrent with the stages of mourning. This case demonstrates a shift from using a photograph as a catalyst to placing it as an integral part of the therapeutic process. The abstract and ambiguous nature of the photos acts as a powerful force in their effectiveness as projectives. The images also encourage free association and help the patient realize salient underlying themes in their lives. The stream of thought brought forth by the photographs provides ongoing feedback and contributes to the patients' creations of new mental images, which translates into increased self-awareness.

Adult

Forearm fractures in children. Cast treatment with the elbow extended.

Fractures of the proximal forearm in young children may be unstable with the elbow flexed but stable with it in extension. Fifteen such fractures were managed by immobilisation in long-arm casts with the elbow extended. Only one patient had more than 15 degrees angulation at the time of bony union. All obtained normal elbow movement at two weeks and full forearm rotation at follow-up. No casts fell off. The extended elbow cast is awkward but it provides an alternative to internal fixation for some unstable fractures.

Casts, Surgical

Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein-restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle.

The serum concentration of insulin-like growth factor-I (IGF-I) is reduced in growing rats fed a low-protein diet, and this decrease is age-dependent, being more pronounced in younger animals. To determine whether this decrease in serum IGF-I is related to a decrease in IGF-I mRNA, growing female rats were given free access to either a 15% protein-sufficient or a 5% protein-deficient diet for 1 week. Protein restriction in 4-week-old rats decreased body weight gain by 44% (P less than 0.001 compared with 4-week controls), serum IGF-I concentration by 67% (P less than 0.001) and liver IGF-I mRNA abundance by 51% (P less than 0.001). During week 6, protein restriction for 1 week resulted in a 20% increase in food intake with no change in weight gain, a 38% reduction in serum IGF-I (P less than 0.001 compared with 6-week controls) and a 39% decrease in liver IGF-I mRNA (P less than 0.001). The serum IGF-I concentration was highly correlated (r = 0.80; P less than 0.001) with the hepatic IGF-I mRNA concentration. Skeletal muscle IGF-I mRNA abundance was also decreased significantly by protein restriction (37% at week 4, P less than 0.001, and 24% at week 6, P less than 0.01) and was closely correlated (r = 0.71; P less than 0.001) with body weight gain. Liver GH-binding protein and GH receptor mRNA abundance were reduced by 1 week of protein deprivation at week 6 but not at week 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals