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P N Schultz

Publications and source records attributed to P N Schultz.

At least 19 recordsLinked to original sources
PubMed2001

Adrenocortical carcinoma. Clinical outcome at the end of the 20th century.

BACKGROUND: Adrenocortical carcinoma remains a rare and lethal neoplasm. Effective therapies have not emerged in recent decades. However, medical advances have improved diagnostic techniques and supportive measures; these changes may have a beneficial impact on the natural history of the disease. METHODS: The authors retrospectively analyzed the clinical outcomes of patients with adrenocortical carcinoma registered at the University of Texas M.D. Anderson Cancer Center focusing on patients who received their diagnosis since 1980 and comparing data from those patients with earlier reports. RESULTS: Since 1980, 139 patients have registered at M.D. Anderson Cancer Center with the diagnosis of adrenocortical carcinoma. One-third had evidence of hormone hypersecretion, and one-third had localized disease at diagnosis. Men were affected as frequently as women but tended to be older and have larger tumors at diagnosis. The 5-year survival rate was 60% (Kaplan-Meier analysis). The 30 patients with the longest survival (> 5 years) and the 30 patients with the shortest survival (< 11 months) had no significant differences in age, gender, tumor size, or functionality. However, long-term survivors had significantly less extensive disease. A comparison with patients reviewed in earlier reports from the same institution showed no significant differences in gender predilection, tumor function, or extent of disease. Despite these similarities, patients whose disease was diagnosed since 1980 lived much longer than patients observed in earlier decades. CONCLUSIONS: Despite the lack of significant improvements in early diagnosis and effective therapies, patients with adrenocortical carcinoma are living longer (5-year survival rate, 60%). It is important to revise assumptions regarding the clinical outcomes of patients with this disease.

Adolescent↗
PubMed2001

Primary healthcare provider's lost opportunity to help abused women.

PURPOSE: To determine how often primary care providers have the opportunity to assess and intervene for intimate partner violence (IPV) in a population of women who are known to be experiencing IPV. DATA SOURCES: A convenience sample of 149 abused women presenting to the justice system for protection orders or to file assault charges against in intimate partner were interviewed about the date and reason for her last healthcare visit, whether she had been screened for IPV, and the presence of selected conditions, medication use, and hospitalizations. CONCLUSIONS: Although 86% (n = 128) of the women had sought healthcare services within the previous year, only 24% (n = 36) had been assessed for IPV. IMPLICATIONS FOR PRACTICE: Abused women use healthcare services at higher rates and have more health conditions than non-abused women. Despite recommendations of professional organizations, health providers have low rates of screening for IPV. Universal screening for IPV by nurse practitioners could substantially interrupt ongoing abuse.

Adult↗
PubMed2000

Quinagolide in the management of prolactinoma.

OBJECTIVE: This study reports a six year experience with quinagolide (CV205-502) in the treatment of 40 patients with hyperprolactinemia or prolactinoma. PATIENTS AND MEASUREMENTS: Forty patients with hyperprolactinemia were treated with quinagolide (CV 205-502, Norprolac) for 2-72 months (mean 31.6 months). The patient's ages ranged from 12 to 53 years and 90% were female. Seventeen had no radiologic evidence of tumor; 11 had microadenomas; and 12 had macroadenomas. RESULTS: All patients had a reduction of the serum prolactin following quinagolide therapy with normalization in 82% with no tumor, 73% with microadenomas, and 67% with macroadenomas. Fifty-five percent of microadenoma and 75% of macroadenoma patients had a decrease in tumor size when assessed by a blinded reviewer. Ten of 38 female patients became pregnant while taking quinagolide. The dosage of quinagolide ranged from 75 to 400 [mgr]g/day with a median dose of 100[mgr]g/day. A comparison of side effects in a subgroup of 35 patients who had taken bromocriptine prior to quinagolide administration showed a greater than 75% reduction in nausea, vomiting, dizziness, and drowsiness during quinagolide administration. CONCLUSIONS: We conclude that quinagolide is a safe and effective long-term alternative to bromocriptine therapy, particularly in those individuals with bromocriptine intolerance.

Adolescent↗
PubMed1999

A codon 891 exon 15 RET proto-oncogene mutation in familial medullary thyroid carcinoma: a detection strategy.

A ser891ala RET proto-oncogene mutation has been previously discovered in a single kindred with familial medullary thyroid carcinoma (FMTC). An additional two probands with this mutation and with medullary thyroid carcinoma (MTC) without any other manifestations of MEN 2 have been identified. In one of thse families, two other individuals also had the mutant sequence and FMTC. Analysis of both cases showed cosegregation of the mutation and MTC. To facilitate detection of this mutation, a primer was engineered which creates a Hha I recognition site in the presence of the mutant sequence. As a result, this codon 891 exon 15 mutation can be identified with a restriction enzyme digestion.

Amino Acid Substitution↗
PubMed1999

Calcium-induced activation of a mutant G-protein-coupled receptor causes in vitro transformation of NIH/3T3 cells.

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that is widely expressed, has tissue-specific functions, and regulates cell growth. Activating mutations of this receptor cause autosomal dominant hypocalcemia, a syndrome characterized by hypocalcemia and hypercalciuria. The identification of a family with an activating mutation of the CaR (Thr151Met) in which hypocalcemia cosegregates with several unusual neoplasms led us to examine the transforming effects of this mutant receptor. Transfection of NIH/3T3 cells with the mutant but not the normal receptor supported colony formation in soft agar at subphysiologic calcium concentrations. The mutant CaR causes a calcium-dependent activation of the extracellular signal-regulated protein kinase (ERK) 1/2 and Jun-N-terminal kinase/stress-activated (JNK/ SAPK) pathways, but not P38 MAP kinase. These findings contribute to a growing body of information suggesting that this receptor plays a role in the regulation of cellular proliferation, and that aberrant activation of the mutant receptor in this family may play a role in the unusual neoplastic manifestations.

3T3 Cells↗
PubMed1999

Screening for MEN1 mutations in patients with atypical endocrine neoplasia.

BACKGROUND: Most patients from typical multiple endocrine neoplasia type 1 (MEN1) kindreds harbor mutations in the MEN-1 gene, MEN1. We hypothesized that some patients with atypical endocrine neoplasia would also have mutations in MEN1. METHODS: DNA sequencing analysis of mutations in the coding region of MEN1 was performed with genomic DNA obtained from peripheral blood lymphocytes in a total of 21 patients who had: typical MEN1 (n = 8), clinical features suggestive of MEN1 but without a family history of endocrinopathy (n = 7), and atypical endocrine neoplasia and a family history of endocrinopathy suggestive of MEN1 (n = 6). RESULTS: All 8 patients with typical MEN1 had mutations in MEN1. None of the 7 patients with features of MEN1, but without a family history of endocrinopathy, had a MEN1 mutation. In contrast, 4 of 6 patients with atypical endocrine neoplasia that included components of MEN1 and a family history of endocrinopathy had mutations in MEN1, including 2 patients with pheochromocytoma. CONCLUSIONS: Genomic mutations in MEN1 may frequently be identified in patients with atypical endocrine neoplasia, especially in the setting of a family history of endocrinopathy. Atypical presentations of MEN1 may include pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1999

Surgical strategy for the treatment of medullary thyroid carcinoma.

OBJECTIVE: To evaluate surgical complications, patterns of lymph node metastases, and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent medullary thyroid carcinoma (MTC). SUMMARY BACKGROUND DATA: The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. These data have provided the rationale for surgeons to perform a more extensive lymphadenectomy at the time of initial thyroidectomy and to consider reoperative cervical lymphadenectomy in patients with persistently elevated calcitonin levels after thyroidectomy. METHODS: Forty patients underwent surgery for MTC from 1991 to 1997 (23 sporadic cases, 17 familial cases). Patients were divided into three groups based on whether they had undergone previous thyroidectomy and on the results of standardized staging studies performed after referral to the authors' institution. Group 1 (11 patients) had received no previous surgery; group 2 (13) underwent thyroidectomy before referral and had an elevated calcitonin level without radiologic evidence of local regional or distant metastases; and group 3 (16) underwent thyroidectomy before referral and had an elevated calcitonin level with radiologic evidence of local-regional recurrence. The central neck compartment was dissected in all patients; preoperative staging and the extent of previous surgery dictated the need for lateral (modified radical) neck dissection. After primary or reoperative surgery, calcitonin levels were assessed. RESULTS: All patients had major reductions in postoperative calcitonin levels. Seven (29%) of 24 patients in groups 1 and 2 achieved normal calcitonin values compared with only 1 (6%) of 16 in group 3. Postoperative complications included seven cases (17%) of permanent hypoparathyroidism; five (71%) of these occurred in group 3. There were no iatrogenic recurrent laryngeal nerve injuries; one patient required recurrent nerve resection to achieve complete tumor extirpation. At a median follow up of 35 months, local recurrence was documented in 5 (13%) of 40 patients. CONCLUSIONS: Compartment-oriented lymphadenectomy performed early in the course of MTC is safe and may return calcitonin levels to normal in up to 25% of carefully selected patients. However, reoperation for bulky cervical disease (group 3) rarely results in normal calcitonin levels and is associated with a high incidence of permanent hypoparathyroidism.

Adolescent↗
PubMed1998

Differentiated thyroid cancer in children and adolescents: clinical outcome and mortality after long-term follow-up.

BACKGROUND: Children and adolescents with differentiated thyroid cancer (DTC) have a good prognosis and prolonged survival even when extensive regional disease or lung metastases are present at the diagnosis; very-long-term follow-up is needed to appreciate what, if any, impact the disease may exert on the ultimate outcome. METHODS: We retrospectively reviewed the clinical course of 112 patients with DTC who registered at M. D. Anderson Cancer Center between 1944 and 1986, were younger than 20 years old at the time of diagnosis, and were followed for at least 10 years. Surgery alone or combined with radioactive iodine or radiotherapy was used for most cases. RESULTS: At the time of most recent contact, 99 patients remained alive and 13 had died. The 99 patients had 25 +/- 0.9 years of available follow-up (mean +/- SEM) and were 41 +/- 0.9 years of age at time of last contact; one fourth had had recurrent disease at some point since diagnosis. Among the 13 patients who died, one died of complications from coexisting diabetes mellitus, and the cause of death was not clear in one other case. Two patients died of breast cancer 13 and 15 years after thyroid cancer diagnosis. In three cases, cause of death could be considered etiologically related to initial radiotherapy: one patient developed tracheal necrosis 26 years after diagnosis and died of upper airway complications, whereas another two patients developed sarcomas of the cervical region 22 and 29 years after thyroid cancer diagnosis. Lastly, six patients died of thyroid cancer 26 +/- 3.1 years after initial diagnosis (at age 40 +/- 2.1 years). Among these cases, one patient had invasive disease and lung metastases at diagnosis and died of progressive lung metastases after 36 years. The other five patients were initially seen with local/regional disease and developed lung and skeletal metastases after a 2- to 20-year disease-free interval. CONCLUSIONS: Our findings support the clinical impression that children and adolescents with DTC live for many years regardless of apparent extent of disease at diagnosis or development of recurrence. Indeed, overall survival was 100% at 10 years even in patients with distant metastases. However, attention to these patients' clinical course beyond the first decade indicates that a small minority (5% to 7%) of patients eventually succumb to progressive disease and that a similar number develop possibly treatment-related lethal complications or second neoplasms. We suggest lifelong surveillance for all such patients.

Adenocarcinoma, Follicular↗
PubMed1998

Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux.

Glial cell line-derived neurotrophic factor (GDNF) mediates signaling across the cell membrane by interaction with the RET-GDNFR alpha receptor complex. We identified a family in which one member had medullary thyroid carcinoma (MTC) and four members had vesicoureteral reflux (VUR). Knowledge that mutations in the RET proto-oncogene cause MTC and studies documenting genitourinary abnormalities in RET or GDNF knockout mice led us to examine the GDNF/RET-GDNFR alpha signaling complex in this family. RET and GDNF were excluded as the causative VUR gene by haplotype and sequence analysis. The GDNFR alpha gene was mapped to chromosome 10q25-26 by radiation hybrid techniques and was eliminated as the causative gene by haplotype analysis and sequencing of cDNA from an obligate carrier. Sequencing identified a 15-nucleotide deletion in GDNFR alpha mRNA, which was found to code for a single exon; analysis of several cell types revealed an identical mRNA form, indicating that this variant is a product of alternative RNA processing. We conclude that GDNFR alpha maps to 10q25-26 and that its RNA transcript is alternatively processed. Mutation abnormalities in the GDNF/RET-GDNFR alpha signaling system do not cause VUR in this family.

Adult↗
PubMed1996

Clinical outcome of patients with papillary thyroid carcinoma who have recurrence after initial radioactive iodine therapy.

BACKGROUND: Among patients with well differentiated papillary thyroid carcinoma who generally have an excellent prognosis and a near-normal lifespan, there exist subsets of patients who have significant risk for morbidity and mortality from this disease. It is important to define the patterns of disease progression and the clinical outcome of such patients to develop effective surveillance and treatment strategies. Patients with recurrence after surgery and therapeutic administration of radioactive iodine (RAI) for papillary thyroid carcinoma represent one such subset of high-risk patients. METHODS: At the University of Texas M. D. Anderson Cancer Center, 65 patients with papillary thyroid carcinoma were diagnosed between 1970 and 1990. Their medical records were reviewed with particular attention to disease recurrence and outcome as well as RAI imaging and treatment. RESULTS: Following diagnosis and initial therapy, 19 patients died from thyroid carcinoma after a median of 64 months; 34 had no evidence of disease for a median of 112 months of available follow-up; and 7 are alive with disease 61 to 153 months after diagnosis. Cervical lymph node metastases were present in 41 patients and extrathyroidal or extranodal tumor invasion was seen in 25 patients at the time of initial surgery; distant metastases (lung, bone, brain, liver, and adrenal) developed later in 18 patients. RAI uptake by recurrent tumor deposits in the neck was seen most frequently in patients with no direct invasion of adjacent tissues but with recurrence limited to cervical lymphadenopathy; this group of patients was the most likely to become clinically and radiologically disease free. RAI generally did not concertrate in invasive cancers with extrathyroidal or extranodal extension in the neck; patients with this type of invasive carcinoma were also more likely to die from the disease. CONCLUSIONS: We suggest that among patients with recurrent papillary thyroid carcinoma, invasive cancers are less likely to concertrate RAI, whereas patients with disease confined to lymph nodes are more likely to have RAI-avid tumors and to benefit from RAI therapy.

Adolescent↗
PubMed1995

Clinical use of molecular information in the management of multiple endocrine neoplasia type 2A.

One hundred and ninety-seven members of 28 kindreds with multiple endocrine neoplasia type 2A (MEN 2A) were screened for RET proto-oncogene exon 10 and 11 mutations. Seventy-one known affected individuals had mutations of codons 609, 618, 620 or 634, whereas 53 unaffected individuals had no abnormalities. Nineteen out of 54 individuals of unknown status, mostly children, had RET mutations. Four of these children had thyroidectomy based on this analysis and were found to have C-cell abnormalities. We identified one false negative mutation analysis because of a codon 691 polymorphism. We conclude that RET mutational analysis is a cost-effective and accurate method for determination of gene carrier status in MEN 2A.

Amino Acid Sequence↗
PubMed1993

Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer.

BACKGROUND: Adrenocortical carcinoma is a rare and aggressive disease with a poor prognosis. Adjuvant mitotane administration has been suggested as a strategy that might improve the outcome of patients with localized disease. METHODS: The authors analyzed the clinical outcome of patients with localized or regional adrenocortical cancer. The study included 19 patients who were registered at M.D. Anderson Cancer Center during a 3-year period and who had localized or regional disease at the time of surgery. Of these, eight patients received mitotane postoperatively and continued the drug until their last contact or recurrence (Group A, adjuvant); five patients began taking mitotane after surgery but discontinued it after 2-12 months for reasons unrelated to the disease (Group P, postoperative); and six patients did not receive mitotane (Group N, no mitotane). All patients have been followed for at least 12 months. RESULTS: The treatment groups differed significantly in their time to recurrence; the disease-free interval was shortest in Group A (P = 0.0055, by log-rank test). There was no statistical difference in survival among the groups, but the profile remained unfavorable for Group A. The 2-year survival rate was 100% for Groups N and P but only 43% for Group A. Of the potentially confounding factors, gender, age, steroid hypersecretion, and tumor size, none had any influence on recurrence or survival rates. CONCLUSIONS: These findings do not support the conclusion that adjuvant mitotane is beneficial in patients with localized or regional adrenocortical cancer. Neither the disease-free interval nor survival was improved by the drug. The authors suggest that alternative therapeutic strategies be explored for the management of these patients.

Adrenal Cortex Neoplasms↗
PubMed1992

The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients.

This study analyzed the impact of prognostic variables of age, sex, histopathological diagnosis, extent of disease at diagnosis, and surgical intervention on well differentiated thyroid carcinoma and how surgical treatment, radioactive iodine, and radiotherapy influence the patients' outcomes. There have been 1599 patients with well differentiated thyroid cancer treated and followed at the University of Texas M.D. Anderson Cancer Center from 1948 to 1989. The median follow-up for all patients was 11.0 yr, with the maximum follow-up being 43 yr and the minimum follow-up being 1 yr. The patients were predominantly female (2.3:1), with papillary (81%) and intrathyroidal carcinomas (42%) at the time of diagnosis. Sixty-six percent of the patients had a total thyroidectomy, 7% received external radiotherapy, and 46% had radioactive iodine as part of the treatment of the original disease; the overall recurrence rate was 23%, and the death rate was 11%. This study showed that treatment with radioactive iodine was the single most powerful prognostic indicator for increased disease-free interval (P less than 0.001) and that its use significantly increased survival as well. No benefit was obtained from treatment with external radiotherapy. Children had the best overall survival, but of the adult patients, females who had intrathyroidal papillary disease treated with total thyroidectomy, who had been given radioactive iodine, and whose disease had been diagnosed between 20-59 yr of age had the best prognosis.

Adolescent↗
PubMed1991

Long-term visual outcome in Terson syndrome.

The presentation and long-term visual outcome in 30 eyes with Terson syndrome is evaluated. In 25 of 30 eyes (83%), visual acuity of 20/50 or better was attained. This occurred in 12 of 16 eyes (75%) managed by observation alone and 12 of 14 eyes (86%) treated by pars plana vitrectomy. The most common long-term sequelae in all eyes studied was the formation of an epiretinal membrane. These occurred in 14 of 18 eyes (78%) followed for 3 or more years but accounted for significant visual loss in only 2 eyes. There was no difference in final visual outcome between those patients undergoing vitrectomy and those managed conservatively. However, visual recovery was more rapid in eyes undergoing vitrectomy despite the fact that vitrectomy was reserved for eyes with more dense vitreous hemorrhage.

Adolescent↗