Datasets:

123rc

/

medical_text

like 4

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

An increase in plasma cholesterol independent of thyroid function during long-term amiodarone therapy. A dose-dependent relationship. OBJECTIVE: To determine whether long-term amiodarone treatment is associated with a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid function. DESIGN: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] less than 2.8 or greater than 22.0 mU/L) either before or during amiodarone treatment. PATIENTS: Twenty-three patients who remained euthyroid were studied. INTERVENTION: Oral administration of amiodarone (mean duration of treatment, 17 months; range, 6 to 30 months). MEASUREMENTS: Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded before and every 6 months during amiodarone treatment. RESULTS: Plasma cholesterol gradually increased from 5.1 +/- 0.2 mmol/L before treatment to 6.9 +/- 0.8 mmol/L after 30 months of amiodarone medication (P less than 0.001); the peak TSH response to TRH did not change. When age- and sex-specific reference values were applied, 30% of the patients had cholesterol values above the 75th percentile before treatment; this number rose to 69% after 2 years of treatment. The rise in plasma cholesterol was associated with an equal increase in apoprotein B. Plasma cholesterol was not related to the daily dose of amiodarone or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4), triiodothyronine (T3), or reverse triiodothyronine (rT3). Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P less than 0.05). CONCLUSION: Long-term amiodarone treatment is associated with a dose-dependent increase in plasma cholesterol that is independent of thyroid function.

Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction. We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated.

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.

False aneurysm formation of the great arteries after arterial switch operation. An infant with simple transposition of the great arteries underwent a two-staged arterial switch operation, after which mediastinal infection occurred. Continuous irrigation with povidone-iodine solution was performed for 10 days. After that, the patient experienced life-threatening hemorrhage three times. At the time of the second hemorrhage, greater omental transfer was performed. On postoperative day 109, false aneurysm was recognized, having developed from both great arteries. Successful repair was performed on postoperative day 110.

Intrinsic vasodilation protects Wistar Kyoto rats from progressive glomerulosclerosis after unilateral nephrectomy. Genetically determined differences in functional and structural determinants that govern the development of progressive glomerulosclerosis (GS) were studied in aging sham-operated or unilaterally nephrectomized male rats of two strains. Wistar rats showed an increase of proteinuria and GS with age, which was enhanced by unilateral nephrectomy (UN). In contrast, intact and UN Wistar Kyoto rats did not show an increase of proteinuria with age and 7 months after UN, no GS was seen in these rats. Systemic blood pressure was comparable in both strains and was not affected by UN. Functional studies in a separate group of rats 1 month after UN showed an identical increase in glomerular filtration rate in both strains as compared with sham-operated controls. The Wistar rats did not show an effect of UN on renal plasma flow, and consequently, there was an increase in filtration fraction, in contrast to Wistar Kyoto rats, which showed an increase in renal plasma flow with an unchanged filtration fraction. Glomerular volume was increased in both strains at 1 month and 7 months after UN. Mesangial expansion was not observed at 1 month after UN in either strain, which indicates that this is not a decisive factor in the development of GS. These data indicate that the genetically determined susceptibility to the development of GS in these two rat strains may be related to the degree of vasoconstriction, whereas glomerular volume expansion per se does not lead to GS but can well be a consequence of hyperfiltration. These studies are concordant with previous studies that revealed the role of hemodynamics in the pathogenesis of GS irrespective of glomerular expansion.

Proximal gastric vagotomy: follow-up at 10-20 years. From August 1969 to December 1989, 600 patients had elective proximal gastric vagotomy for duodenal ulceration with an operative mortality of 0.2 per cent. Of these, 372 patients had surgery over 10 years ago. Three hundred and forty-two patients survived for more than 10 years and, in a prospective study, 305 were reviewed, forming the basis of this 10-20-year follow-up report. Forty-six (15 per cent) have had recurrent ulceration; 80 per cent of these developed symptoms within 5 years and no patient has had recurrence after 13 years. Although 29 patients required reoperation for recurrent ulceration, the current patient satisfaction rate for Visick grades I and II is 92 per cent. Only two patients required reoperation because of gastric stasis. It is concluded that proximal gastric vagotomy is a safe and satisfactory first choice operation for duodenal ulceration.

A randomized control trial of two cervical spatulas The sampling efficacy of the Ayre and Rocket cervical spatulas was compared in a randomized controlled trial involving 533 women who were attending a colposcopy clinic either for investigation of cytological abnormality or for review after treatment of CIN. Smears were compared with respect to the presence of cytological abnormality and two types of normal cervical epithelial cells (endocervical and immature metaplastic cells) which are considered indicators of adequate cytological sampling. Smears taken with the Rocket spatula were significantly less likely to contain immature metaplastic cells (95% CI on difference in proportion; 5-30%), but more likely to contain endocervical cells (95% CI 16-36%). No significant difference was found in the proportion of smears containing one or other type of indicator cell or in the yield of abnormal smears. It is concluded that the Rocket spatula offered no advantage when used in these circumstances. This study illustrates how spurious conclusions of sampling efficacy can be drawn if only one type of indicator cell is used as an endpoint.

The 1989 presidential address. International Society for the Study of Vulvar Disease. Major changes in the terminology for vulvar disease have taken place in the past 20 years under the influence of the members of the International Society for the Study of Vulvar Disease. Major terminology changes have been made for vulvar nonneoplastic disorders, vulvar intraepithelial neoplasia and superficially invasive squamous cell carcinoma.

Detection of vascular complications in renal allografts with color Doppler flow imaging. One hundred ninety-five color Doppler flow (CDF) examinations were performed in 146 renal allografts to assess the capabilities of this technique in detecting intra- or extrarenal vascular complications. Conventional angiography was also performed in 44 transplants. In the group of transplants with angiographic correlation, CDF sonography enabled correct identification of 30 of 34 vascular complications. CDF showed 10 of 11 significant stenoses of the renal artery or of one of its main branches. There were two false-positive renal artery stenoses (one normal artery and one 40% stenosis). Nine of nine renal artery thromboses and the single pseudoaneurysm were also identified. Within the parenchyma, CDF sonography demonstrated five of five segmental infarcts, two of two postbiopsy arteriovenous fistulas, and three of six segmental or interlobar artery stenoses. Measurement of peak systolic velocity showed a significant difference (P less than .05) between a group (n = 8) with significant stenosis of the renal artery or one of its main branches (mean, 215.2 cm/sec +/- 32) and a group (n = 14) without stenosis (mean, 99.2 cm/sec +/- 19).

Social support and the cancer patient. Implications for future research and clinical care. This review assesses past progress, current practices, and future needs in research and clinical practice involving the social support needs of cancer patients. A review is given of the various conceptualizations of the social support/stress paradigm and of the state of the art of measuring social support. Then the current work in the field of social support and cancer is considered and an argument is made for the use of social support measures, which are relevant to the experiences of the cancer patient. Potential adaptations of an existing instrument (the Duke-UNC Functional Social Support Scale) are demonstrated, and a taxonomy of stages of cancer that would require additional types of social support measures and interventions is outlined. Interventions are discussed in terms of the traditional support groups as well as interventions by the oncologist and primary care physician. An argument is made for the inclusion of quality of life or functional measures as outcomes in clinical trials and the care of the cancer patient. Finally, the need to address the existential, philosophic, or religious issues surrounding cancer and its treatment is discussed.

Have changing treatment patterns affected outcome for operable breast cancer? Ten-year follow-up in 1288 patients, 1965 to 1978. From 1965 to 1978, 1288 patients with primary operable breast cancer were treated by the senior author, using extended radical (ERM), radical (RM), and modified radical (MRM) mastectomy operations exclusively. Results were analyzed for trends in overall and disease-free survival, and patterns of local and distant relapse, the years 1965 to 1970 versus 1971 to 1974 versus 1975 to 1978. Significant changes (p less than 0.00001) from 1965 to 1978 included progressively earlier stage of disease, less frequent use of RM and ERM, a decline in the use of postoperative radiotherapy, and the introduction in 1975 of multidrug adjuvant chemotherapy. Ten-year disease-free survival rates improved significantly for all patients (by 11%, p = 0.00004) and for node-negative (by 12%, p = 0.0024), node-positive (by 8%, p = 0.012), clinical stage II (by 15%, p = 0.0022), and pathologic stage II (by 12%, p = 0.016) disease. Ten-year local recurrence for all patients was 3% (local only) and 2% (local with distant metastasis), and survival from date of recurrence for all patients failing treatment increased two times (p less than 0.0001) for patients treated most recently. As the primary surgical treatment of breast cancer continues to become more moderate, the promise of systemic adjuvant therapies can be realized only with continued emphasis on earlier diagnosis and maximal local control of disease.

Acute leukemia and related entities. Impact of new technology. Twenty-seven cases of acute leukemia and related entities were evaluated by morphologic examination, cytochemical study, terminal deoxynucleotidyltransferase study, immunophenotyping, cytogenetic analysis, ultrastructural cytochemical study, and gene rearrangement analysis to determine the impact on the determination of the French-American-British (FAB) classification and the definitive diagnosis. The definitive diagnosis contained prognostic, diagnostic, and treatment information beyond the FAB classification that affected the disease course and patient management. All diagnostic variables were evaluated in each case and were labeled essential, ambivalent, supportive, or noncontributory. Except for gene rearrangement analysis, all variables we studied contributed essential data to establish the definitive diagnosis. Ambivalent findings were rare but could be explained with the knowledge of the total data. All variables, except cytochemical study, whose results were almost always essential, contributed supportive data. Noncontributory data only occurred with cytogenetic analysis in cases that demonstrated normal karyotypes. The FAB classification was established in 20 (74%) of the cases by use of morphologic examination, cytochemical study, and terminal deoxynucleotidyltransferase study. With use of the same variables, however, the definitive diagnosis, whose determination required all data, was established in only 15 (55.5%) of the cases. The addition of immunophenotyping increased the definitive diagnosis to 25 (92.5%) of the cases. The use of ultrastructural myeloperoxidase and platelet peroxidase analysis enabled us to definitively diagnose the remaining two cases (27 cases [100%]). Cytogenetic analysis revealed four cases in which essential information was added to the diagnosis. However, because the cytogenetic information usually was not immediately available, the result did not affect the immediate diagnosis or treatment. Surprisingly, the gene rearrangement studies did not yield essential data in any case and in a few cases contributed ambivalent data. This finding should not exclude gene rearrangement analysis in selected cases; however, the data should always be interpreted in light of all clinical and laboratory findings. This study clearly demonstrates the importance of a multifaceted approach to the understanding of the acute leukemias and related entities and shows the impact of newer technologies on reaching a definitive diagnosis.

Synchronous diffuse well-differentiated lymphocytic lymphoma and gastric adenocarcinoma presenting as splenomegaly and iron deficiency anemia. Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed.

Antibiotic use among children in an urban Brazilian slum: a risk factor for diarrhea? [published erratum appears in Am J Public Health 1991 Apr;81(4):417] Among a cohort of children in a poor urban setting in Brazil, the relative risk for the occurrence of a new episode of diarrhea in the two weeks following antibiotic use vs all other weeks was 1.44 (95% confidence interval (CI) = 1.33, 2.45). Among children ever [corrected] exposed to antibiotics, the odds ratio was 1.34 (95% CI = 0.84, 2.16) after stratifying by individual child and controlling for previous diarrhea. Further research is needed to confirm whether antibiotics are a risk factor for diarrhea in such settings.

Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions We developed and validated a radioimmunoassay for circulating human parathyroid hormone-related peptide (PTHrP), based on a commercial antiserum to the synthetic 1-34 fragment of PTHrP, 125I-Tyr degrees-PTHrP(1-34) as radioligand, and prior extraction of the native peptide from plasma with C-2 cartridges. We determined immunoreactive PTHrP concentrations in plasma samples from 48 healthy persons (mean +/- SD, 3.1 +/- 1.0 pmol/liter; range, less than 2 to 5 pmol/liter), 8 patients with primary hyperparathyroidism, 36 patients with hypercalcemia and a concurrent malignant lesion, and 9 normocalcemic patients with cancer and increased serum levels of carcinoembryonic antigen or prostate-specific antigen. PTHrP was normal in samples from patients with primary hyperparathyroidism (3.2 +/- 1.1 pmol/liter), secondary hyperparathyroidism (2.5 +/- 1.3 pmol/liter), and cancer without hypercalcemia (2.4 +/- 1.0 pmol/liter). In contrast, plasma immunoreactive PTHrP levels were increased (6.0 to 85.0 pmol/liter) in 47% of patients with hypercalcemia and cancer of various types, with or without bone metastatic lesions. Large amounts of PTHrP were also found in conditioned medium from cultured human prostatic carcinoma cells. Thus, PTHrP may be a causative factor for hypercalcemia associated with a malignant lesion in at least half of the cases. Measurement of circulating PTHrP may be of differential diagnostic help in hypercalcemic states.

Posterior transfer of the adductors in children who have cerebral palsy. A long-term study. Seventy-eight posterior transfers of the adductors of the hip in forty-two children who has spastic cerebral palsy were reviewed an average of 5.7 years after the operation (range, two to 14.6 years). The results were assessed on the basis of the patient's ability to walk, the range of motion of the affected hip or hips, and the radiographic measurements. In 88 per cent of the patients, the transfer was successful in improving or maintaining abduction, extension, functional walking, and stability of the hip. The failures were all in patients who were unable to walk and who had spastic quadriplegia. Tenotomy of the iliopsoas tendon at the time of the transfer procedure resulted in an improved range of motion of the hip.

Cancer registry problems in classifying invasive bladder cancer. A slide review of diagnostic pathologic tissue obtained from 364 bladder cancer cases, identified through the Iowa Surveillance, Epidemiology, and End Results (SEER) Program in 1983, classified 97 (26.6%) of these cases as invasive bladder cancers. These findings contrasted sharply with the Iowa SEER Program classification that coded 289 (79.4%) of these cases as invasive bladder cancers. These results were validated further by the hazard ratio of 4.54 (95% confidence interval, 2.57 to 8.03) among invasive relative to noninvasive bladder cancer cases when the slide review findings were used. In contrast, the hazard ratio was only 1.70 (95% confidence interval, 0.76 to 3.79) when the Iowa SEER Program findings were used. The traditional method used by the National Cancer Institute's SEER Program to deal with this problem is described and its implications are discussed.

Solitary, isolated metastasis from Ewing's sarcoma to the brain: case report. We report a case of a 30-year-old woman who developed an intraparenchymal cerebral metastasis from a Ewing's sarcoma of the chest wall diagnosed and treated 3 years earlier and in apparent remission at the time of the neurological presentation (seizures). The case was complicated by a spontaneous preoperative intratumoral hemorrhage that occurred the morning of the scheduled surgical resection and caused a left dense hemiparesis. The tumor and the hematoma were removed. The patient improved after surgical intervention and a postoperative course of cranial irradiation followed by systemic chemotherapy was given. Nineteen months after treatment the patient remains disease-free from the clinical and radiological standpoint.

Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Regulation of insulin secretion involves the coordinated control of ion channels in the beta-cell membrane. We have isolated and characterized cDNA and genomic clones encoding a voltage-dependent K+ channel isoform expressed in human islets and in a human insulinoma. This K+ channel isoform, designated hPCN1, with a deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the Shaker family of Drosophila K+ channels. hPCN1 is homologous to two other human K+ channel isoforms we have isolated, hPCN2 and hPCN3, with 55% and 65% amino acid sequence identity, respectively. The electrophysiological characteristics of hPCN1 were determined after microinjection of synthetic RNA into Xenopus oocytes. Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA revealed a voltage-dependent outward K+ current that inactivated slowly with time. Outward currents were inhibited by 4-aminopyridine with a Ki less than 0.10 mM and were relatively insensitive to tetraethylammonium ion or Ba2+. A delayed rectifier K+ channel such as hPCN1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion.

Learning a unimanual motor skill by partial commissurotomy patients. A series of motor tests on four Chinese partial commissurotomy patients is reported. The single-stage commissurotomy in all four patients included the anterior commissures and two-thirds or four-fifths section of the corpus callosum with sparing of the splenium. There was no demonstrable ability to transfer hand posture in these patients. This was the major evidence for functional deconnexion. A newly learned task of one-hand knotting revealed right hand impairment in all four patients. There was no dyspraxia in the right hand for over-learned object-handling tasks in these patients. It is suggested that there might be right hemisphere specialisation for the initial acquisition of unimanual object-handling skills and that the spared callosal fibres in the splenium alone are insufficient to mediate task control under these conditions. This is supported by the finding that one of these patients, who was the only one who had a right parietal lesion, was unable to perform the newly learned task with either hand.

Linkage of early-onset familial breast cancer to chromosome 17q21. Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

Long-term followup of asymptomatic microhematuria. We present a 10 to 20-year followup assessment of 191 patients with unexplained microhematuria (including persons with insignificant lesions). Genitourinary malignancies did not develop in any of the patients (128 alive and 27 dead) evaluated after the first diagnostic investigation. Patient and physician compliance with followup protocols was poor. We currently recommend renal ultrasound and cystoscopy for the first diagnostic survey, have abandoned routine periodic studies and advise diagnostic studies only for patients in whom symptoms develop.

Ocular manifestations of onchocerciasis in a rain forest area of west Africa. The epidemiology and natural history of onchocerciasis and its ocular complications in rain forest areas are poorly understood. The present study was conducted on a rubber plantation in a hyperendemic area in the rain forest of Liberia, West Africa, where 800 persons were examined. The prevalence of infection was 84% overall 29% had intraocular microfilariae, and 2.4% were blind in one or both eyes. Onchocerciasis was the cause of all binocular blindness and one-third of all visual impairment. Over half of the visual impairment caused by onchocerciasis was due to posterior segment diseases. Chorioretinal changes were present in 75% of people, and included intraretinal pigment clumping in 52% and retinal pigment epithelium atrophy in 32%. Atrophy of the retinal pigment epithelium was associated with increasing age and severity of infection. Intraretinal pigment was strongly associated with anterior uveitis. There was a strong correlation between uveitis and the inflammatory chorioretinal sequelae: retinitis, intraretinal pigment, subretinal fibrosis, and optic neuropathy. These findings indicate that considerable visual impairment associated with rain forest onchocerciasis is common and is due largely to chorioretinal disease.

Cells immunoreactive for neuropeptide in human thymomas. The presence of opioid peptides, bombesin, and substance P was investigated by immunohistochemistry in tissue sections from six human thymomas. The number of immunoreactive cells seemed to vary from one case to another. Ultrastructural investigation, showing the presence of desmosomes in labelled cells, allowed these cells to be classified as epithelial lineage cells. The occurrence of cells containing neuropeptide in thymomas suggest that peptide molecules could have modulated the behaviour of this tumour, given the reported influence of these molecules on immune functions and their growth promoting activity on several cell types, including mesenchymal and epithelial cells.

Sphincter preservation in rectal cancer by local excision and postoperative radiation therapy. The authors report the preliminary results of 14 patients with localized, mobile, resectable rectal cancer treated with local excision and postoperative radiation therapy (RT). All had negative surgical resection margins and two received 5-fluorouracil (5-FU). The median follow-up was 29 months (4-43 months). The 3-year actuarial survival was 88%. The incidence of local failure was 7% (only site of failure) and 21% (component of failure). The incidence of local failure increased with T stage (T1, 0/3 [0%]; T2, 1/7 [14%]; and T3, 2/4 [50%]) and tumor size (greater than 3 cm, 33%, versus less than or equal to 3 cm, 0%). Three patients developed local failure at 6, 15, and 21 months. Three underwent a salvage abdominoperineal resection and were locally controlled at 2 and 28 months following salvage surgery. One patient underwent an abdominoperineal resection for a clinically presumed local failure; however, no tumor was found in the specimen. Therefore, the 13 patients who either were initially locally controlled or underwent salvage or nonsalvage surgery had no evidence of disease in the pelvis at the time of last follow-up. Local excision and postoperative RT may be an alternative to standard surgery in selected cases. However, additional follow-up and more experience are needed in order to determine if this approach will ultimately have local control and survival rates similar to those of a low anterior resection or an abdominoperineal resection.

One-stage laryngotracheoplasty. This article documents the evolution of our approach to the repair of subglottic stenosis in infants. With increasing experience in the management of subglottic stenosis using the anterior cricoid split procedure, we extended our procedure to include older children. This then led to the use of the one-stage procedure for repair of severe and mature subglottic stenosis. We present the results of surgical repair in 13 patients. Extubation was accomplished in 12 of 13 patients using one-stage laryngotracheoplasty.

Results of transsphenoidal extirpation of craniopharyngiomas and Rathke's cysts. Fourteen patients undergoing transsphenoidal extirpation of craniopharyngiomas or Rathke's cysts underwent endocrinological evaluation before and after surgery. One patient died during the procedure because of uncontrollable arterial bleeding. The other patients were followed for up to 16 years (average, 8.5 years). One patient had recurrence of tumor 12 years after surgery. Another patient, the only one operated on because of a recurrent craniopharyngioma after previous radiation therapy, died 2 years after the transsphenoidal operation. No patient recovered pituitary functions that had been lost before surgery. One patient, who had an isolated growth hormone deficiency, and another, who had panhypopituitarism with sustained antidiuretic hormone secretion, had no change postoperatively from their preoperative endocrine status. The other 11 patients lost pituitary function and required pharmacological replacement of one to four pituitary hormones.

Breast cancer: the military's experience at Wilford Hall USAF Medical Center. We reviewed the experience with breast cancer at Wilford Hall USAF Medical Center for the years 1978 through 1988. A total of 868 cases were identified in the Wilford Hall Tumor Registry; overall 5-year and 10-year survivals were 63% and 39%, respectively. Infiltrating ductal carcinoma represented the principal histologic category. The other predominant variants included invasive lobular carcinoma, lobular carcinoma in situ, and ductal carcinoma in situ. Until recently, most of these patients (90%) had modified radical mastectomy as their definitive surgical therapy, with chemotherapy reserved primarily for patients with advanced disease.

Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model. BACKGROUND. We report that rapid atrial pacing interrupts atrial flutter when the orthodromic wave front from the pacing impulse is blocked in an area of slow conduction in the reentry circuit. To characterize the area of slow conduction during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile pericarditis. METHODS AND RESULTS. Atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the interruption of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec. Areas of slow conduction during atrial flutter were demonstrated at one to three sites in the reentry circuit. After rapid pacing captured the reentry circuit, one area of slow conduction either disappeared (10 episodes) or the degree of slow conduction in an area of slow conduction decreased (one episode). Both changes were in association with activation of the region by a wave front from the pacing impulse that arrived from a direction different than that during the induced atrial flutter. Interruption of atrial flutter during rapid pacing occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction that had either newly evolved during rapid pacing (seven episodes) or that was previously present (four episodes). CONCLUSIONS. Areas of slow conduction present during atrial flutter and rapid pacing of atrial flutter are functional and depend on both the atrial rate and the direction of the circulating wave fronts. Interruption of atrial flutter by rapid pacing results from block of the orthodromic wave front of the pacing impulse in an area of slow conduction in the reentry circuit.

Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: a Doppler echocardiographic study. Patients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension. The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 +/- 0.11 versus 0.32 +/- 0.09; p less than 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 +/- 2.2 versus 8.6 +/- 1.2 cm2/m2; p less than 0.005). Acting as a receiving chamber, the left ventricle was maximally compressed by the volume-overloaded right ventricle in late diastole, coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 +/- 0.14 versus 1.03 +/- 0.1; p less than 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling.

Effects of acute alcohol intake on tolerance to hypotension. The specific aim of this research was to test the hypothesis that intoxication with alcohol results in poor tolerance to hemorrhage. This was evaluated on the basis of blood pressure, cardiac output respiratory rate, blood flow to organs, and survival for 4 hr after hemorrhage. Four groups of six swine per group were used (control, intoxicated, hemorrhage, and intoxicated-hemorrhage). The results revealed that blood alcohol concentrations near 0.1% greatly reduced tolerance to hemorrhage. Intoxicated animals subjected to hemorrhage were unable to maintain an adequate cardiac output, blood pressure, or respiratory rate to sustain life. Pigs tolerated higher blood alcohol concentrations, up to 0.35%, when not exposed to hemorrhage. Also, unintoxicated pigs were able to compensate for severe hemorrhage. Only one of the six pigs in the intoxicated-hemorrhage group survived for 4 hr after hemorrhage. In conclusion the body's ability to compensate and recover from hemorrhage was greatly reduced during intoxication. It is logical to assume that the ability to overcome numerous other stressors may also be reduced during intoxication.

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension. To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.

An angiographic technique for three-dimensional determination of arterial supply patterns in cadaver soft tissue. A method for arterial tree mapping that can be used in cadaver soft tissue is presented. In situ angiograms and photographs are supplemented with profile angiograms of relatively narrow bands of tissue from the removed specimen. The described method was better suited for mapping the course and supply patterns of a soft-tissue arterial network than either in situ angiograms or dissection. While practical problems were encountered with most of the solutions used for providing radiopacity or structural support to the vessels, pure barium sulfate was found to be suitable because it filled the vascular tree to the capillary level without leakage during excision of the specimen.

Myocardial temperature during cardiac operations: influence on right ventricular function. Maintenance of right heart integrity is frequently neglected during coronary operations. Right ventricular dysfunction sometimes limits the success of the surgical procedure, however. In addition to the use of cardioplegic solutions, myocardial hypothermia during ischemic cardiac arrest seems to be an important factor for guaranteeing right ventricular performance thereafter. This study was designed to measure myocardial temperature in patients with coronary artery disease who have significant stenosis of the right coronary artery in comparison with those who do not have stenosis of the right coronary artery and to evaluate the influence of myocardial temperature on right ventricular hemodynamics after cardiopulmonary bypass. Right ventricular function was assessed by thermodilution technique, which allows measurement of right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume. Right ventricular temperature differed significantly between the two groups, with the lowest value of 15.1 degrees +/- 1.8 degrees C in the group without stenosis of the right coronary artery and a value of 22.2 degrees +/- 2.1 degrees C in the group with stenosis of the right coronary artery. Left ventricular and septal temperatures were without group differences within the investigation period. Right ventricular hemodynamics were impaired only in the group with stenosis of the right coronary artery with a decrease in right ventricular ejection fraction from 44.2% to 34.1% immediately after termination of bypass and an increase in right ventricular end-diastolic volume index (+38%) and right ventricular end-systolic volume index (+70%). Cardiac index decreased only in this group, too (-22.5%). Analysis of covariance revealed a significant correlation only between changes in right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume and the course of right myocardial temperature. It is concluded that right ventricular hypothermia is more difficult to achieve in patients with a diseased right coronary artery. Constant myocardial hypothermia, however, seems to be important in guaranteeing right ventricular function, which easily can be evaluated by the thermodilution technique.

Headache and acquired immunodeficiency syndrome. Because the acquired immunodeficiency syndrome (AIDS) virus is neurotropic, physicians will continue to see a rise in the number of neurologic complications of this syndrome. Much of this increase will be accompanied by headache, not only as a primary symptom of HIV infection or opportunistic disease but also as a result of diagnostic tests and therapeutic efforts. Complete understanding of the ramifications of headache in AIDS will be important in the 1990s as we continue to treat a younger population, usually affected by benign vascular and muscle contraction-type headache.

Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started.

Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats. The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195 +/- 8 to 125 +/- 5 and 148 +/- 3 mm Hg, respectively [mean +/- SEM]; p less than 0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911 +/- 155 to 1,244 +/- 101 and 1,388 +/- 59 microns 2, respectively, compared with 1,405 +/- 95 microns 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 +/- 6 to 62 +/- 2 mm Hg with cilazapril versus 79 +/- 5 mm Hg for hydralazine compared with 60 +/- 4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 +/- 4 to 100 +/- 4 microns for cilazapril versus 91 +/- 3 microns for hydralazine compared with 107 +/- 3 microns for untreated WKY rats).

Quantitation of G0 and G1 phase cells in primary carcinomas. Antibody to M1 subunit of ribonucleotide reductase shows G1 phase restriction point block. Human cancers have an apparent low growth fraction, the bulk of cells presumed to being out of cycle in a G0 quiescent state due to the inability in the past to distinguish G0 from G1 cells. The allosteric M1 subunit of ribonucleotide reductase (M1-RR) is constitutively expressed by cycling cells (i.e., G1, S, G2-M). It is acquired during transition from G0 to G1, lost during exit to G0 and thus distinguishes G0 from G1 cells. To estimate the proportion of G0 and G1 cells in primary human breast (n = 5) and colorectal (n = 12) adenocarcinomas, we used both analytical DNA flow cytometry (ADFC) and immunoperoxidase staining of sections with the monoclonal antibody to M1-RR (MAb M1-RR). ADFC of fresh tumors revealed a low percentage of cells in the S phase (4.0 +/- 3.4%) but immunoperoxidase staining for M1-RR revealed an unexpectedly high proportion of positive cells (52.4 +/- 12.7%) in the G1, S, G2-M phases indicating a high G1 content of primary human tumors. Thus, human cancers are blocked in transition in G1 and are not predominantly in a G0 or quiescent differentiated state. This block was interpreted to mean that human cancers are responding to putative regulatory events at a restriction point in the G1 phase, such as relative growth factor deficiency, density inhibition, antiproliferative cytokines, or gene products. Using flow cytometry for both DNA and M1-RR content we found that human colon cancer cell lines arrest in the G1 but not G0 phase upon serum deprivation or density inhibition. Similarly, human breast cancer cell lines are arrested in G1 but not G0 phase by medroxyprogesterone acetate (MPA) or tamoxifen exposure. These findings match our in situ observations, and support the concept of a restriction point block in primary human tumors.

Elevated serum bromide concentrations following repeated halothane anaesthesia in a child. A 20-month-old child received 25 brief halothane general anaesthetics over a five-week period to allow cranial irradiation treatments for a posterior fossa ependymoma. Personality change during the last week of the treatment protocol raised the question of possible bromide intoxication. Serum bromide concentrations, using a gold chloride assay technique, were monitored at that time, and at four- and six-week intervals thereafter. Serum bromide concentrations demonstrated a four-fold change during this period ranging from peak levels of 2.2 mEq.L-1 (176 micrograms.kg-1) during the fifth week of treatment decreasing to less than 0.5 mEq.L-1 (less than 40 micrograms.ml-1) six weeks following the end of treatments. This demonstrates the possibility for repetitive, short halothane exposures to result in elevations of serum bromide and the potential of bromide intoxication in paediatric neuro-oncology patients.

Prognostic value of reduced heart rate variability after myocardial infarction: clinical evaluation of a new analysis method. The relation between heart rate variability, measured from standard 24 hour electrocardiogram recordings in patients convalescent after a myocardial infarction, and the occurrence of sudden death and spontaneous, symptomatic, sustained ventricular tachycardia were assessed in a consecutive series of 177 patients admitted with acute myocardial infarction and surviving to 7 days. In addition to the analysis of heart rate variability, the occurrence of non-sustained arrhythmias on 24 hour electrocardiographic monitoring, and the results of clinical assessment, signal averaged electrocardiography and ejection fraction were analysed and were related to outcome. During a median of 16 months of follow up (range 10-30 months) there were 17 end point events (11 (6.2%) sudden deaths) and six (3.4%) episodes of sustained ventricular tachycardia. An index of the width of the frequency distribution curve for the duration of individual RR intervals was used to measure heart rate variability. This mean (SD) index was significantly smaller in those with end point events (16.8 (8.0)) than in those without events (29.0 (11.2)). The relative risk of the occurrence of an end point event in those with a heart rate variability index less than 25 was 7.0. Multivariate analysis showed that of all the variables examined a reduced heart rate variability index was the single most powerful predictor of end point events. Measurement of heart rate variability by this simple, automated, operator-independent method provided useful information on the arrhythmic propensity in patients convalescent after myocardial infarction.

Oral labetalol in hypertensive urgencies. The response to incremental doses of oral labetalol in 16 patients with hypertensive urgencies is presented. After inadequate blood pressure control with 20 mg of intravenous furosemide, each patient received a 300 mg oral dose of labetalol. Subsequent oral doses of labetalol, 100 mg, were administered at 2-hour intervals, if the diastolic blood pressure remained greater than 100 mm Hg. The maximum dose of labetalol per patient was 500 mg. Five patients required only the initial 300 mg dose of labetalol. Two patients required further therapy for satisfactory blood pressure control. Mean arterial pressure fell from 156 +/- 12 mm Hg to 123 +/- 14 mm Hg.

Clinical problems in follow-up of patients after conservative surgery and radiotherapy. Patients treated with conservative surgery and radiotherapy for early-stage breast carcinoma are at risk of developing an ipsilateral breast recurrence for a long period. Fortunately, few such patients present with an inoperable recurrence or simultaneous distant metastases. Salvage rates are high and may be improved by early detection. Although usually unambiguous, physical examination of the treated breast may reveal changes attributable to surgery and radiotherapy that can mimic a recurrent cancer. There also is substantial overlap in radiologic appearance between benign and malignant lesions. It may be necessary to perform a biopsy when there is a question of recurrence. Careful life-long follow-up of patients thus is a critical part of their care.

Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro. Strains of Epstein-Barr virus (EBV) with deletions of the small RNA (EBER) genes were made by homologous recombination using the EBV P3HR-1 strain, which has undergone deletion of the essential transforming gene that encodes the EBV nuclear antigen, EBNA-2, and a DNA fragment that was wild type at the EBNA-2 locus but from which the EBER genes had been deleted. Even though the EBER and EBNA-2 genes are separated by 40 kilobases, selection for transforming P3HR-1 recombinants that required a restored EBNA-2 gene resulted in 20% cotransfer of the EBER deletion. EBER-deleted recombinants transformed primary B lymphocytes into lymphoblastoid cell lines (LCLs), which were indistinguishable form LCLs transformed by wild-type EBV in their proliferation, in latency-associated EBV gene expression, and in their permissiveness for EBV replication cycle gene expression. EBER-deleted virus from infected LCL clones could infect and growth-transform primary B lymphocytes. These procedures should be applicable to the construction of other EBV recombinants within 40 kilobases of the EBNA-2 gene. The EBER-deleted EBV recombinants should be useful in further evaluating the role of EBERs in EBV infection.

Urinary tract infection in women. Current role of single-dose therapy. Administration of a single dose of an antimicrobial agent is acceptable therapy for women with uncomplicated lower urinary tract infections. There is adequate information in the literature to support the clinical use of single-dose therapy, although there is still a need for further, well-designed, sufficiently large studies that compare single-dose therapy to abbreviated-course (3-day) and traditional (7- to 14-day) therapy.

Hoarseness as the sole presenting symptom of foramen magnum meningioma. Foramen magnum tumours are rare. They may present with bizarre symptoms and mimic many conditions. We report a presentation with the sole complaint of hoarseness, never previously described in the literature. Voice returned to normal after surgical removal of the foramen magnum meningioma.

Cryptic osteoid osteoma of the cranium: case report. Osteoid osteoma is an uncommon benign tumor of bone that rarely involves the cranium. If often causes local pain that is worse at night, characteristically relieved by aspirin, and does not correlate with the size of the lesion. The diagnosis depends on skull radiographs and computed tomography. This report describes a case in which radiographs showed nothing abnormal. The diagnosis and operative localization were accomplished with radionuclide bone scanning. Thus, the possibility of radiographically cryptic lesions must be considered in the evaluation of atypical head pain syndromes.

Postural hypotension: pressor effect of octreotide not mediated by norepinephrine. Orthostatic hypotension of the Shy-Drager syndrome is a chronic incapacitating condition characterized by lack of an appropriate increase in the plasma norepinephrine level in response to standing. Recently, the somatostatin analogue octreotide has been reported to induce a pressor response in patients having this syndrome. We have reported a case of Shy-Drager syndrome in which octreotide was effective, but the rise in blood pressure was not accompanied by an increase in the plasma norepinephrine level. Hence, the pressor effect of octreotide is not mediated by stimulation of the sympathetic nervous system, but probably through splanchnic vasoconstriction.

Outcome among surviving very low birthweight infants: a meta-analysis. Because published outcome studies are the only available source of data about the morbidity among surviving very low birthweight infants (VLBW, less than 1500 g) a search was carried out of 1136 references in the English language. A total of 111 outcome studies were found that reported morbidity data in cohorts of VLBW infants born since 1960. The methods used and results obtained in these studies were systematically assessed. No agreement exists about the definition of study populations, descriptive statistics, or measurement of outcome. Follow up ranged from six months to 14 years. In 85 cohorts the incidence of cerebral palsy was recorded, and in 106 that of disability. Studies that followed up infants for longer time periods reported higher incidences of disability. Studies from the United States reported higher incidences of disability than those from other countries. The median incidence of cerebral palsy among all the cohorts studied was 7.7%, and the median incidence of disability was 25.0%. Despite substantial improvements in the mortality of VLBW infants, poor outcomes among survivors are common.

Circumflex artery ventricular fistula and pseudoaneurysm after mitral reoperation. Prosthetic mitral valve reoperation complicated by atrioventricular groove pseudoaneurysm and circumflex ventricular fistula is presented. Ligation of the circumflex artery during mitral valve replacement is implicated after review of a previous cardiac angiogram.

The efficacy of azathioprine in relapsing-remitting multiple sclerosis. We randomized 59 patients with relapsing-remitting multiple sclerosis to receive azathioprine (AZA) 3.0 mg/kg daily or placebo in a double-masked therapeutic trial. Analysis of data for predetermined primary outcome measures demonstrated a significant difference favoring AZA for observed mean exacerbation rate after 2 years of therapy and time to deterioration in both Ambulation Index and Kurtzke Expanded Disability Status Scale score. This study confirms a modest therapeutic benefit for azathioprine previously reported by other investigators.

Persistent neutrophilic meningitis. Persistent neutrophilic meningitis is an unusual but distinct clinical variant of chronic meningitis characterized by CSF neutrophilia with hypoglycorrhachia which persists for more than 1 week on serial CSF studies. Documented etiologies include selected bacteria and higher bacteria such as Brucella, Nocardia and Actinomyces as well as "opportunistic" fungi such as Candida, Aspergillus, the Zygomycetes, and Pseudallescheria. Recognition of the syndrome is important, as empiric therapy (e.g., cotrimoxazole and amphotericin B) may differ significantly from that used for classic chronic meningitis.

Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.

Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography. The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization.

Mandibular involvement in oral cancer. It is difficult to predict the tumour invasion into the mandible by oral cancer pre-operatively, and consequently the decision to preserve or sacrifice the mandible is largely individualistic. The present study of 44 cases analyses the reliability of pre-operative parameters to assess mandibular involvement. Clinical, radiological and scintigraphic features have been compared with the detailed histology of the bone. This study confirms the usefulness of superior marginal resections in lesions which are close to but not involving the mandible, as well as for superficial lesions which are actually seen to involve the mandible but their CT and bone scans are negative for tumour invasion.

Mechanical factors in large artery disease and antihypertensive drugs. Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis.

Effects of FUdR on primary-cultured colon carcinomas metastatic to the liver. Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo.

Pseudotumor of the craniocervical junction during long-term hemodialysis. A systematic study of the upper cervical spine was performed using magnetic resonance imaging in 25 patients (15 men and 10 women) who had been undergoing hemodialysis for more than 10 years. Seven pseudotumors of the periodontoid soft tissue were disclosed, which were similar to the pannus recently described in rheumatoid arthritis. Bone cystic radiolucencies were observed in association with these pseudotumors in 5 patients. The radiolucencies were located in the atlas (1 in the lateral mass and 1 in the anterior branch) and in the axis (3 in the odontoid process and 1 in the vertebral body). No horizontal or vertical atlantoaxial subluxation was demonstrated. These features were observed only in patients who had amyloid arthropathy. They could be a frequent, yet thus far little-recognized, feature of beta 2-microglobulin amyloidosis.

Islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices. Report of a case and review of the literature. Gastrointestinal hemorrhage from left-sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas. Islet cell tumors of the pancreas themselves are rare. They present in a variety of ways. Those that elaborate functional hormones cause specific neuroendocrine syndromes. Nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement. We present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation. We emphasize the importance of a careful initial diagnostic work-up that may enable curative surgery.

Efficacy of acebutolol after acute myocardial infarction (the APSI trial). The APSI Investigators. A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of beta blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether beta-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (greater than or equal to 20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol-treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors.

A protocol for butalbital, aspirin and caffeine (BAC) detoxification in headache patients. The abuse of the combination drug containing butalbital 50 mg, aspirin 325 mg and caffeine 40 mg (or BAC), is commonly recognized by headache specialists as causing headaches. Despite this widespread problem, there is not a published treatment regimen for the BAC detoxification of patients. I describe such a protocol which was used four times in three patients. These patients fulfilled the diagnostic criteria of the IHS Headache Classification for headaches induced by chronic substance abuse (8.2) and analgesics abuse headache (8.2.2). These patients took between 150 and 420 BAC/month for 2-15 years. Two patients had previously undergone inpatient detoxification. One patient unsuccessfully tried detoxification twice as an outpatient. All patients were required to have psychological support prior to hospitalization for this protocol. BAC was discontinued. A pentobarbital challenge test corroborated butalbital dosage. The patients were given phenobarbital and caffeine which were tapered over several days. Dihydroergotamine (DHE) with metoclopramide was used (Raskin). Propranolol 60 mg bid was started. No narcotics were permitted. After hospital discharge, patients were allowed to continue subcutaneous DHE, as needed. One patient restarted BAC use after 8 months without it. The other two patients were still BAC free 18 and 14 months after detoxification.

The effect of muscle-sparing versus standard posterolateral thoracotomy on pulmonary function, muscle strength, and postoperative pain. Increased interest in alternative approaches to thoracotomy has developed because of the considerable morbidity associated with the standard posterolateral technique. We conducted a prospective, randomized, blinded study of 50 consecutive patients to compare postoperative pain, pulmonary function, shoulder strength, and range of shoulder motion between the standard posterolateral and the muscle sparing thoracotomy techniques. Pulmonary function (forced expiratory volume in 1 second and forced vital capacity), shoulder strength, and range of motion were measured preoperatively and at 1 week and 1 month postoperatively. Pain was quantitated by postoperative narcotic requirements, the visual analogue scale, and the McGill pain questionnaire. Morbidity, mortality, and hospital stay were compared between the standard posterolateral and muscle-sparing techniques. There were no differences in postoperative pulmonary function, shoulder range of motion, extent of lung resection, surgical approach time, mortality, or hospital stay. There was significantly less postoperative pain in the muscle-sparing group. The narcotic requirement was less in the first 24 hours (p = 0.0169), and visual analogue scale scores were significantly lower (p less than 0.05) throughout the first postoperative week. Shoulder girdle strength was decreased at 1 week in the standard incision group whereas the strength was preserved with the muscle-sparing approach. Muscle strength had returned to preoperative levels by 1 month in both groups. Morbidity was identical in the two groups with the exception of postoperative seromas. The prevalence of seroma was 23% in the muscle-sparing group and 0% in the standard incision group (p = 0.0125). We have demonstrated that the muscle-sparing incision may be a reasonable alternative to the standard posterolateral approach.

Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases. In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers.

Coronary arteries in truncus arteriosus. The origin and distribution of the coronary arteries was described in 39 autopsy specimens of truncus arteriosus (TA). The specimens were classified according to the number and the patterns of the truncal cusps. The position of the truncal cusps was defined in relation to intracardiac structures, namely, the atrioventricular orifices. Bicuspid truncal valves were observed in 8 cases (21%), tricuspid in 22 cases (56%) and quadricuspid in 9 cases (23%). All tricuspid valves had 2 anterior and 1 posterior cusp. Great variability in the origin of the coronary arteries was observed, with a tendency for the right coronary artery to arise from the anterior right quadrant and for the left coronary artery to arise from the anterior and left quadrant. Such a tendency was observed in 50% of the bicuspid, in 59% of the tricuspid and in 66% of the quadricuspid valves. The anatomic right ventricle was always observed to be vascularized by a right coronary artery, and the anatomic left ventricle by a left coronary artery, even in cases in which there was a single coronary trunk. The anterior surface of the right ventricle was crossed by a right coronary artery in 5 cases. A single coronary artery was observed in 7 cases (18%). Embryologic considerations are offered, especially regarding the relation between the observed variability in coronary artery patterns in TA and the absence of the truncal septation.

Hemoperitoneum as a result of coital injury without associated vaginal injury. Hemoperitoneum as a result of coital injury without associated vaginal injury is an extremely rare entity, and evidence by only five cases that have been reported in the medical literature to date. We report five additional cases encountered in two medical centers. Two of these were ruptured corpus luteum cysts, one was a laceration of the round ligament, another was a laceration of an ovary, and the fifth was rupture of a serous cystadenoma. This diagnosis should be considered in patients with hemoperitoneum after coitus.

The use of cognitive behavior therapy with a normalizing rationale in schizophrenia. Preliminary report. Sixty-four consecutively referred patients with schizophrenia were treated with cognitive-behavioral psychotherapy as an adjunct to standard treatment. A destigmatizing rationale to explain symptom emergence was devised and supplemented these techniques. They proved safe to use and appeared acceptable to patients and their relatives. Members of the group are being maintained on low levels of or no medication and have required minimal hospitalization. The techniques used are described in detail.

Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia. We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using 18F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.

Macrophage colony-stimulating factor activity in malignant pleural effusions. Its augmentation by intrapleural interleukin-2 infusions. The activity of endogenous colony-stimulating factor (CSF) in malignant pleural effusions of lung cancer patients before and during daily intrapleural infusions of recombinant interleukin-2 (IL-2) was measured quantitatively by colony-forming bioassay and radioimmunoassay (RIA). Before therapy, malignant pleural effusions had various levels of CSF activities, and this CSF activity was neutralized almost completely by anti-M-CSF antibody. RIA also showed that the effusions contained various amounts of M-CSF. Daily intrapleural infusion of recombinant IL-2 caused significant increase in the CSF activities and M-CSF levels in pleural effusions. These results indicate that in vivo treatment with IL-2 induces production of endogenous M-CSF.

Histologic evaluation of the width of soft tissue necrosis adjacent to carbon dioxide laser incisions. This study evaluated the width of tissue necrosis lateral to carbon dioxide laser incisions on human intraoral excisional biopsy specimens. Measurements were made on specimens including epithelium, muscle, dense and loose connective tissue, and salivary gland. Results showed a mean width of tissue necrosis of 86 microns in epithelium, 85 microns in muscle, 51 microns in loose connective tissue, 96 microns in dense connective tissue, and 41 microns in salivary gland. The range of thermal necrosis in different tissue types is probably based on the water content within each type. A cellular partially homogenized zone of reversible thermal damage up to 500 microns in width was visible adjacent to the zone of thermal necrosis. The relatively narrow width of tissue necrosis with this technique may account for the claimed superior properties of laser-induced wounds compared with those created by electrosurgery.

Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure.

Osteoid osteoma of the scapula. A case report and review of the literature. The scapula is a rare location for osteoid osteoma, which in most cases does not involve the flat bones. The en bloc excision in this uncommon location can be problematic since the surgical exposure is difficult, and shoulder joint function can be affected if the lesion is subchondral. In an 18-year-old man, an osteoid osteoma was located in the subchondral area of the glenoid. A guided needle biopsy of the nidus resulted in complete healing. This mode of treatment, with proper follow-up examination, is acceptable for a benign lesion situated in a problematic location.

High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. The purpose of this study was to estimate the incidence and to establish which factors were associated with an increased risk of hemorrhagic complications in an historic cohort of 117 consecutive and unselected patients with chronic idiopathic thrombocytopenic purpura (ITP). Sixty-eight patients (58%) underwent medical treatment and/or splenectomy and 33 (48% of treated) achieved a complete stable remission. At equivalent platelet count the incidence of major hemorrhagic complications was significantly higher in aged (greater than 60 years) than in younger (less than 40 years) patients (10.4% v 0.4%/pt-y, relative risk = 28.9, P less than .01). A previous hemorrhagic event was identified as another major risk factor for hemorrhage (relative risk = 27.5, P less than .0005), while hypertension and underlying disorders had no influence. We conclude that age more than 60 years and a previous history of bleeding are major risk factors for severe hemorrhages in adults with ITP.

A retroviral promoter is sufficient to convert proto-src to a transforming gene that is distinct from the src gene of Rous sarcoma virus. The src genes of four natural isolates of avian sarcoma viruses differ from cellular proto-src in two genetic substitutions: the promoter of the cellular gene is replaced by a retroviral counterpart, and at least six codons from the 3' terminus are replaced by retroviral or heterologous cell-derived elements. Since virus constructs with a complete proto-src coding region failed to transform avian cells but acquired transforming function by point mutations of various codons, it has been proposed that point mutation is sufficient to convert proto-src to a transforming gene. However, promoter substitution is sufficient to convert two other proto-onc genes, proto-ras and proto-myc, to retroviral transforming genes. In view of this, we have reexamined whether promoter substitution, point mutation, or both are necessary to convert proto-src into a retroviral transforming gene. It was found that a recombinant virus (RpSV), in which the src gene of Rous sarcoma virus (RSV) was replaced by the complete coding region of proto-src, transformed quail and chicken embryo cells. The oncogene of RpSV differs from the src gene of RSV in three genetic properties: (i) it is weaker--e.g., transformed cells are flatter; (ii) it is slower--e.g., focus formation takes 9 to 12 days compared to 4 days for RSV; and (iii) its host range is narrower than that of RSV--e.g., only subsets of heterogeneous embryo cells are transformed by RpSV even after weeks or months. Replacement of the proto-src 3' terminus of RpSV by that of src from RSV generates a recombinant virus (RpvSV) that equals RSV in transforming function. It is concluded that a retroviral promoter, naturally substituted via illegitimate recombination with retroviruses, is sufficient to convert at least three proto-onc genes, src, myc, and ras, to retroviral transforming genes.

Two types of abnormal somatosensory evoked potentials in chronic cerebellar ataxias. To investigate subclinical sensory impairment in spinocerebellar degenerations, median nerve somatosensory evoked potentials (SEPs) were examined in 16 patients with chronic cerebellar ataxia who were originally diagnosed by clinical neurologists as having olivopontocerebellar atrophy (OPCA). Two types of abnormal SEP patterns were found in six patients. Two patients had the SEP pattern of peripheral neuropathy, which was also detected by peripheral sensory nerve conduction studies. Four patients had abnormal SEPs seen in patients with the lesions in the central nervous system (dorsal column, medial lemniscus). Magnetic resonance imaging (MRI) showed multiple sclerosis (MS). It is possible that clinically diagnosed OPCA sometimes includes a similar form of Friedreich's ataxia with subclinical sensory fiber neuropathy detected by SEPs and peripheral sensory conduction studies. In cases of lesions in the central nervous system demonstrated by both SEPs and MRI, there must be a follow-up in order to make a final diagnosis. In those cases, an alternative diagnosis of MS must be considered when the temporal profile of symptoms and signs characteristic of MS is observed.

Late outcome of survivors of out-of-hospital cardiac arrest with left ventricular ejection fractions greater than or equal to 50% and without significant coronary arterial narrowing. In a retrospective survey of 1,195 survivors of out-of-hospital ventricular fibrillation, 43 patients were identified in whom left ventricular ejection fraction was greater than or equal to 0.50 and in whom no coronary artery stenosis of greater than or equal to 50% luminal diameter were present. Thirteen (30%) of these patients had hypokinesia on left ventriculography, and 20 patients (47%) had a persistently abnormal electrocardiogram. Seven patients (16%) had recurrent out-of-hospital cardiac arrest during an average follow-up of 86 +/- 54 months. The presence of either wall motion or electrocardiographic abnormalities defined patients with a several-fold higher risk of recurrent cardiac arrest than those without such abnormalities. The risk for recurrent cardiac arrest within 5 years was 30% in those with abnormal electrocardiograms versus 5% in the others (p less than 0.03). Age was an independent predictor of recurrent cardiac arrest in this group (p less than 0.01); surprisingly, recurrent cardiac arrest was occurring more often among younger patients. Although cardiac arrest is unusual in patients without major structural heart disease, its recurrence in such survivors is common. Patients at relatively high risk for recurrent ventricular fibrillation can be identified by their youth and by abnormalities detected on the surface 12-lead electrocardiogram or by contrast left ventriculography.

Injection or heat probe for bleeding ulcer. A prospective randomized trial was performed to compare the efficacy of endoscopic epinephrine injection and heat probe treatment in actively bleeding peptic ulcers. Emergency endoscopy in 1758 patients over an 18-month period identified 132 patients with active ulcer bleeding. They were randomized to receive either endoscopic epinephrine injection or heat probe treatment. After endoscopy, the patients were transferred to the surgical gastroenterology ward and were managed by surgeons unaware of the treatment option. Bleeding was initially controlled in 96% by epinephrine injection and in 83% by heat probe (P less than 0.05). There was no significant difference in outcome as measured by transfusion requirement (4.5 units vs. 3.8 units), emergency surgery (20% vs. 22%), hospital stay (8 days vs. 7 days), and mortality (2 vs. 4) between the injection group and the heat probe group. Two patients in the heat probe group experienced perforation. We conclude that both endoscopic epinephrine injection and heat probe treatment are effective in stopping bleeding from actively bleeding ulcers. Epinephrine injection is technically easier to perform and has a higher initial success rate.

Management of premature removal of the percutaneous gastrostomy. Percutaneous endoscopic gastrostomy (PEG) has become the preferred method of enteral access for nutritional support. With increased use of this modality, complications are encountered more frequently. Premature withdrawal, inadvertent removal of the gastrostomy tube within the first seven days after insertion, before adherence of the gastric serosa to the parietal peritoneum, has been an indication for laparotomy. This report describes the treatment of premature withdrawal by immediate endoscopic replacement. Over an 18-month period, 271 patients underwent insertion of a PEG. Five patients (1.8%) who inadvertently removed their gastrostomy tube within seven days of insertion were treated with immediate replacement using the retrograde string technique, avoiding laparotomy. All five PEGs were successfully replaced through the same gastrostomy site. Despite the presence of pneumoperitoneum, no patient developed peritonitis or other septic complications. Premature gastrostomy tube withdrawal is safely managed by endoscopic replacement and observation. Laparotomy is unnecessary and potentially meddlesome.

Transoesophageal echocardiography improves the diagnostic value of cardiac ultrasound in patients with carcinoid heart disease. Transthoracic and transoesophageal cardiac echocardiography and Doppler investigations were performed in 31 consecutive patients with malignant midgut carcinoid tumours. The transoesophageal images allowed measurement of the thickness of the atrioventricular valve leaflets and the superficial wall layers on the cavity side of both atria. The mean thickness of the anterior tricuspid leaflet was significantly greater than that of the mitral valve--a difference not seen in a control group of age-matched patients without carcinoid tumours and with normal cardiac ultrasound findings. In addition, the edges of the tricuspid leaflets were thickened giving them a clubbed appearance. Tricuspid incompetence was detected transoesophageally in 71% of the patients with carcinoid compared with 57% by transthoracic investigation. The inner layer of the right atrial wall in the carcinoid patients was significantly thicker than that of the left atrium and that of both atria in the controls. Furthermore, patients with other signs of severe carcinoid heart disease had significantly thicker mean right atrial luminal wall layer than those with less or no signs of right heart disease. Transoesophageal cardiac ultrasound investigation improved the diagnostic accuracy and seemed to show the structural changes typical of carcinoid heart disease established by histopathological investigations.

Combined laryngeal framework medialization and reinnervation for unilateral vocal fold paralysis. The laryngeal framework-Silastic implant technique has become an increasingly attractive alternative to Teflon injection, particularly when there is fixation of the cricoarytenoid joint or the defect to be corrected is larger than usual; but it does not restore ability to change tension in the vocal fold. Unilateral vocal fold reinnervation can overcome this drawback and, when used in conjunction with surgical medialization, may offer return of function very close to normal. Twenty-nine patients with unrecovered unilateral vocal fold paralysis and/or fixation of the cricoarytenoid joint have been managed by use of a Silastic implant combined with unilateral vocal fold reinnervation with no complications. Voice improvement has been assessed on preoperative and postoperative voice recordings. The combined surgical techniques for reinnervation and a modification of Silastic implantation via the laryngeal framework approach are reported.

Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.

Anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging. Five anally continent nulliparas of reproductive age were studied with magnetic resonance imaging. The internal and external anal sphincters could be easily delineated, as could the intervening longitudinal musculature, puborectalis muscle, anococcygeal raphe, anorectal lumen, vagina, uterus, bladder, urethra, coccyx, and pubis. The shape of the sphincters was nearly cylindrical, with an anterior component averaging 18.3 mm thick and 28.0 mm long. Fifty-four percent of this anterior thickness was attributable to the internal sphincter. The anorectal angle varied considerably, with a mean of 86.8 +/- 19.1 degrees (range 60-112). The angle between the portion of the rectal lumen supported by the anococcygeal raphe, or levator plate, and the plane of the puborectalis muscle was consistent at 149.0 +/- 6.3 degrees (138-154). The finding of anterior anal sphincters with substantial thickness and length contrasts markedly with a view often pictured in the literature of a female anal sphincter that narrows anteriorly to half its posterior length and forms a small bundle of muscle rather than a broad band. Knowledge of these relationships is important in primary repair of obstetric sphincter lacerations as well as in surgical correction of anal incontinence.

The nature and course of olfactory deficits in Alzheimer's disease. OBJECTIVE: The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits. METHOD: Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test. Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant. RESULTS: Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed. There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects. On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced. Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not. CONCLUSIONS: Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder. The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not "begin in the nose," as has been theorized previously. Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia.

Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study Group OBJECTIVE--To compare the efficacy of angiotensin converting enzyme inhibition with calcium antagonism in diabetic patients with microalbuminuria. DESIGN--Randomised study of diabetic patients with microalbuminuria treated with perindopril or nifedipine for 12 months and monitored for one or three months after stopping treatment depending on whether they were hypertensive or normotensive. Patients were randomised separately according to whether they were hypertensive or normotensive. SETTING--Diabetic clinics in three university teaching hospitals. PATIENTS--50 diabetic patients with persistent microalbuminuria. In all, 43 completed the study: 30 were normotensive and 13 hypertensive; 19 had type I diabetes and 24 had type II diabetes. INTERVENTIONS--For 12 months 20 patients were given perindopril 2-8 mg daily and 23 were given nifedipine 20-80 mg daily. MAIN OUTCOME MEASURES--Albumin excretion rate, blood pressure, and glomerular filtration rate. RESULTS--Both perindopril and nifedipine significantly reduced mean blood pressure. During treatment there was no significant difference between those treated with perindopril and those treated with nifedipine with respect to albuminuria or mean blood pressure. Stopping treatment with both drugs was associated with a sustained increase in albuminuria and mean blood pressure. There was a significant correlation between mean blood pressure and albuminuria and also between the reduction in mean blood pressure and the decrease in albuminuria during treatment with both drugs. In hypertensive patients both drugs caused significant decreases in mean blood pressure and albuminuria. In normotensive patients there was no significant reduction in albuminuria with either regimen. CONCLUSIONS--In diabetic patients with microalbuminuria blood pressure seems to be an important determinant of urinary albumin excretion. Perindopril and nifedipine have similar effects on urinary albumin excretion, both preventing increases in albuminuria in normotensive patients and decreasing albuminuria in hypertensive patients.

Acetazolamide-responsive vestibulocerebellar syndrome: clinical and oculographic features. Five patients who presented with long-standing episodic vertigo had ocular motor signs localizing to the vestibulocerebellum. In each patient, the episodic vertigo was either abolished or markedly decreased in frequency and severity with acetazolamide therapy. In 4, other family members had identical symptoms and signs. This syndrome is 1 of the few treatable causes of chronic episodic vertigo.

Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. This study determined whether opiates alter vascular components of inflammation (hyperthermia, edema and plasma extravasation) in addition to the suppression of hyperalgesia. Rats were administered carrageenan into one hind paw and saline into the other hind paw, followed by i.p. injection of morphine (0.2-5.0 mg/kg) or saline at 60 min, and testing at 90 min after hind paw injections. Morphine produced a dose-dependent reduction in carrageenan-induced hyperalgesia (17-53%), hyperthermia (39-53%) and edema (24-36%). Morphine treatment did not alter the temperatures of the contralateral saline-injected paws, indicating that opiate suppression of hyperthermia was not confounded by alterations in systemic body temperature or blood flow. The opiate effects on inflammation were stereospecific since levorphanol (1 mg/kg), but not dextrorphan (1 mg/kg), suppressed carrageenan-evoked hyperalgesia, hyperthermia and edema. Pre-treatment with naltrexone (1.5 mg/kg) blocked the effects of a 5 mg/kg dose of morphine sulfate on hyperalgesia, hyperthermia and edema. In a separate study, i.v. injection of morphine sulfate (2 mg/kg) reduced plasma extravasation by 41% (P less than 0.01). Morphine administration resulted in significantly greater increases in paw withdrawal latencies in the inflamed (38-139%) than the contralateral, saline-treated paws (4-19%). The results indicate that opiates exert a moderate, though significant, reduction in the vascular signs of inflammation in addition to their reduction of hyperalgesia. The mechanisms for this vascular effect involve inhibition of both vasodilation (as indicated by a decrease in hyperthermia) and inhibition of vascular permeability. In addition, opiates exhibit enhanced antinociceptive effects in inflamed paws, even when compared to uninjured paws in the same animal.

Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism. Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart. On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin. The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium. There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes were, however, not matched by an increase in myocardial substrate uptake. "Oxygen wastage" of FFA metabolism at high circulating catecholamine levels is suggested. There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine and insulin were demonstrated. The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs. Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.

Learning disabilities in epilepsy: neurophysiological aspects. Subclinical generalized spike-wave discharges are often accompanied by transitory cognitive impairment, demonstrable by psychological testing during EEG recording. Transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike-wave bursts lasting for more than 3 s, but can also be found during briefer and even focal discharges. That this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity: left-sided focal spiking is more likely to produce errors on verbal tasks, for instance, whereas right-sided discharges are more often accompanied by impairment in handling nonverbal material. Both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges. However, there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities. The significance of transitory cognitive impairment accompanying subclinical EEG discharges for everyday functioning is uncertain, but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists. In some individuals, suppression of discharges by antiepileptic drugs has demonstrably improved psychological function, but further work is required to determine the indications for such treatment.

Benzodiazepine tranquilizers and the risk of accidental injury. To determine whether benzodiazepine tranquilizers increase the risk of accidental injury requiring medical attention, we used pharmacy claims submitted to a large third-party payer to identify 4,554 persons who had been prescribed these agents and a matched control group of 13,662 persons who had been prescribed drugs other than benzodiazepines. We then used diagnoses recorded on claims submitted by medical care providers to identify all accident-related care received by these persons during three months before their first-observed prescription for a benzodiazepine or nonbenzodiazepine agent, respectively, and six months subsequently. We found accident-related care was more likely among persons who had been prescribed benzodiazepines; among these persons, the probability of an accident-related medical encounter was higher during months in which a prescription for a benzodiazepine had recently been filled compared to other months; and persons who had filled three or more prescriptions for these agents in the six months following initiation of therapy had a significantly higher risk of an accident-related medical event than those who had filled only one such prescription. Approximately two-fold risks of accident-related care were found, after controlling for age, sex, and prior utilization.

Age-related hypotensive effect of placebo and active treatment in patients older than 60 years. European Working Party on High Blood Pressure in the Elderly. Elderly hypertensive patients were randomly assigned to active treatment (n = 365) or placebo (n = 377). The effects of treatment on blood pressure were calculated by subtracting pretreatment blood pressure from the blood pressure at 3 months. In the two treatment groups, the decrease in systolic and diastolic pressures was more pronounced in older patients. However, the slopes of blood pressure change with age were not significantly different in the two treatment groups: systolic, -0.47 and -0.37 mm Hg/year in the active-treated and placebo patients, respectively; diastolic, -0.26 and -0.15 mm Hg/year, respectively. Thus, proving that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo.

Femoro-popliteal and femoro-distal bypass: a comparison between in situ and reversed technique. The present report compares the in situ technique with that using the reversed vein for femoropopliteal bypass. In 1986 the in situ technique was introduced at our clinic as the preferred method for femoropopliteal bypass with the lower anastomosis below the knee or femorodistal bypass. Forty patients operated with the in situ technique were compared with an equal number of patients operated with the reversed technique 1983-1985. The two groups were comparable regarding concomitant cardiovascular and pulmonary disease, preoperative ankle-brachial index and level of distal anastomosis. Patency after 6 months was significantly higher (84%) for the in situ grafts compared to reversed veins (49%). The difference was mainly caused by a significantly higher patency for in situ grafts anastomosed to infrapopliteal arteries. Despite better patency rates in the in situ group limb salvage at 6 months was the same in both groups. Operating time was also similar in both groups. It is concluded that the in situ technique is superior to the reversed technique, at least in infrapopliteal reconstructions. The superior patency rate and the technical advantages without apparent disadvantages are the basis for the recommendation to use the in situ technique for femoropopliteal and femorodistal bypass.

Choroidal osteoma (osseous choristoma): an atypical case. A case of choroidal osteoma presenting in a 22-year-old girl is reported. The tumour, unilateral and in a juxtapapillary site, appeared markedly elevated on the retinal plane, not flat or slightly elevated as in previous reports. Visual acuity was not affected, and there was a complete absence of subjective symptoms. Echography, fluorangiography, computerised tomography, and visual field tests were performed. Echography is the best method for identifying and differentiating this lesion from a malignant tumour.

Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis.

Cervical lymph nodes from an unknown primary tumor in 190 patients. Over 10 years, 475 patients with isolated lateral neck masses were evaluated: 190 with lymph nodes from an unknown primary tumor (LNUP), 188 with neck lymphomas, 78 with benign tumors, 10 with sarcomas, and 9 with chemodectomas. This study focused on the patients with LNUP. Only 86 patients were treated with surgery (plus radiotherapy). Other patients were treated with radiotherapy (84) or chemotherapy (13) or had no treatment (7). For the overall population, failures in the neck occurred in 51% of the patients and distant metastases in 27%, while primary tumors appeared in 16%. Survival rates at 3, 5, and 10 years were 27%, 19%, and 7%, respectively, for the overall population and 45%, 35%, and 19%, respectively, for the surgical group. The diagnosis and therapeutic approach had a direct effect on neck control; failure in the neck occurred in 7 of 47 patients (15%) when fine needle aspiration and radical neck dissection with radiotherapy were performed, in 5 of 12 patients (42%) when fine needle aspiration and modified neck dissection with radiotherapy were used, in 5 of 12 patients (42%) when adenectomy diagnosis and radiotherapy treatment were performed, and in 6 of 11 patients (54%) when diagnosis by incisional biopsy was performed prior to admission, despite subsequent radical neck dissection and radiotherapy treatment. In our opinion, panendoscopy and fine needle aspiration should be the first-line diagnostic approach. When cytologic diagnosis proves impossible, the second-line approach must consist of cervical exploration with frozen section examination and excisional biopsy, followed by immediate appropriate treatment. In cases of LNUP, radical neck dissection seems to be preferable.

Multivariate analysis in the prediction of death in hospital after acute myocardial infarction. Prognostic factors in patients with acute myocardial infarction based on clinical and investigative data on admission were evaluated prospectively in 111 consecutive patients. Seventeen patients (15.3%) died during hospital stay. Age, a previous infarct, high Killip class, cardiomegaly, high serum concentrations of cardiac enzymes, a low ejection fraction, and a high wall motion score index correlated significantly with in-hospital mortality; whereas sex, risk factors, and pericardial effusion did not. Multivariate analysis showed that age and the wall motion score index were the best predictors of death in hospital. Wall motion detected by cross sectional echocardiography may reflect the extent of myocardial involvement. Age and wall motion score index predicted in-hospital mortality with a sensitivity of 76.5%, a specificity of 91.5%, and a predictive accuracy of 89.2%. Age and the wall motion score index can be determined on admission and are useful for identifying patients at high risk of cardiac death who might benefit from early intervention.

Saltpeter ingestion. A 37-year-old man presented to the emergency department after an attempt to self-treat his priapism with saltpeter (K+NO3). Initially he had a potassium of 7.6 with electrocardiographic changes and a markedly elevated CO2. The potassium and carbon dioxide normalized in less than 24 hours with standard treatment for hyperkalemia. Hyperkalemia is expected with large oral potassium ingestion; and the elevated CO2 was spurious, caused by the misreading of serum nitrates by the Ektachrom 700 system. Ingestion of K+NO3 should be added to the differential of hyperkalemia with a markedly elevated CO2.

Clinicopathologic studies of children who die of acute lower respiratory tract infections: mechanisms of death. Clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined. The mechanism of death for these patients was multifactorial. Severe pneumonia alone accounted for 11 deaths (15.5%). Pneumonia associated with sepsis occurred in 42 children (59.2%). Heart failure (8.5%), hypovolemia (4.2%), and nosocomial infection (12.6%) were also seen in children with fatal acute lower respiratory tract infection. Extensive consolidation, squamous metaplasia, and hyaline membranes were present in the lungs of these children. Patients with severe disease must receive, in addition to antibiotics for acute episodes, individualized intensive respiratory and supportive care. Since these types of care are not available in poor communities, vaccination against measles and vitamin A supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease.

Castor bean intoxication. We report the cases of a child who ingested two or more castor beans and two adults who each ingested four beans. All three patients developed severe gastroenteritis and recovered without sequelae after receiving IV fluids. The literature contains reports of 424 cases of castor bean intoxication. Symptoms of intoxication include acute gastroenteritis, fluid and electrolyte depletion, gastrointestinal bleeding, hemolysis, and hypoglycemia. Delayed cytotoxicity has not been reported. Of the 424 patients, 14 died (mortality rates: 8.1% of untreated and 0.4% of treated). Deaths were due to hypovolemic shock. Recommended treatment for asymptomatic patients who have chewed one or more raw beans is emergency department evaluation, gastric decontamination, administration of activated charcoal, observation until four to six hours after ingestion, and discharge instructions to return if symptoms develop. After decontamination and activated charcoal, symptomatic patients require hospitalization for treatment with IV fluids, supportive care, and monitoring for hypoglycemia, hemolysis, and complications of hypovolemia. Monitoring for delayed cytotoxicity is unnecessary. Castor beans and their dust are highly allergenic and may cause anaphylaxis.

Is obesity-related hypertension less of a cardiovascular risk? The Framingham Study. The hypothesis that obesity-related hypertension is relatively innocuous was explored by an examination of cardiovascular events over 34 years of follow-up when related to biennially measured weights and blood pressures using time-dependent covariate proportional hazards analysis. The 5209 participants were also classified by age, cigarette smoking, and antihypertensive treatment at each of four baseline examinations with 8-year follow-up periods. Over the period of follow-up, there were 978 cardiovascular events in men and 836 in women. Risk of cardiovascular morbidity and mortality in general and of CHD in particular was as strongly related to hypertension at all levels of body mass index. This was also found to apply when adjustment was made for possible confounding by cigarette smoking. Age and smoking-adjusted absolute risks of cardiovascular events were found to be higher in hypertensive individuals with high than with low BMIs. Furthermore, the relative risk of cardiovascular disease did not vary significantly with BMI. Thus hypertension is at least as dangerous in obese as in lean persons at all ages in either sex, providing no support for the hypothesis that hypertension in the obese is more benign. This is important, since obesity predisposes to hypertension and most who have hypertension are obese. This report examines the hypothesis for CVD outcomes considered by previous reports and also the subcategories of CVD disease such as myocardial infarction and stroke, and includes data on both men and women and on young and old.

Peritoneal closure or non-closure at cesarean. The value of peritoneal closure at the time of cesarean birth was evaluated prospectively. Two hundred forty-eight women undergoing low transverse cesarean through a Pfannenstiel skin incision were assigned to one of two groups: peritoneum open (N = 127) or peritoneum closed (N = 121). The mean (+/- SEM) surgical time in the open group (48.1 +/- 1.2 minutes) was significantly less than for the closed group (53.2 +/- 1.4 minutes) (P less than .005). There were no postoperative differences between the groups in the incidence of wound infection, dehiscence, endometritis, ileus, and length of hospital stay. Our study suggests that leaving the parietal peritoneum unsutured is an acceptable way to manage patients at cesarean delivery.

Embryonal carcinoma of the testis presenting as a left heart mass. A 31-year-old man with a history of intravenous drug abuse and tooth abscess was admitted for evaluation of possible infective endocarditis. Echocardiography showed that he had a left atrial mass. The mass removed from the left atrium had the same histology as the primary embryonal carcinoma discovered in the right testicle during hospitalization. The patient made a smooth recovery after surgical intervention and chemotherapy. This is believed to be the first reported case of metastasis from embryonal carcinoma of the testis to the left side of the heart that was successfully removed at surgery.