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Biomedical subjects

G Ramirez

Publications and source records attributed to G Ramirez.

At least 19 recordsLinked to original sources

Immunocytochemical localization of proANF 1-30, proANF 31-67 and atrial natriuretic factor in the kidney.

ProANF [1-30 first 30 amino acids (a.a) of the 126 a.a atrial natriuretic factor (ANF) prohormone], ProANF 31-67 (a.a 31-67) as well as atrial natriuretic factor (a.a 99-126), of the ANF prohormone localized to the sub-brush border of the pars convoluta and pars rectus of the proximal tubules of hydrated and dehydrated rat kidneys with immunoperoxidase staining. Immunofluorescent studies revealed that each of these peptides and especially ProANF 31-67 had a strong predilection for the perinuclear region in the proximal and distal tubules. ProANFs 1-30, 31-67, and 99-126 (that is, ANF) also localized with both immunoperoxidase and immunofluorescent staining to the cortical collecting ducts, glomeruli, peritubular, and interstitial blood vessels. ProANF 31-67 immunoperoxidase staining was particularly striking in the elastica of the small and large interstitial arteries. The whole prohormone being present was suggested by immunological recognition in the rat kidney of both the N-terminus and C-terminus of the ANF prohormone by radioimmunoassays. The concentration of the N-terminus in the kidney was 1.0 +/- 0.03 ng/g of kidney weight, while the C-terminus of the ANF prohormone concentration was 0.4 +/- 0.01 ng/g of kidney tissue. These findings of a sub-brush border and perinuclear location of the N-terminal and C-terminal ANF prohormone peptides suggest that the atrial natriuretic factor prohormone may be synthesized in and/or the respective peptides are captured by the proximal tubules, but also to a lesser extent by the distal tubules of the kidney.

Animals

Is combination sulfonylurea and insulin therapy useful in NIDDM patients? A metaanalysis.

OBJECTIVE: To assess the efficacy of combination therapy with insulin and sulfonylurea in the treatment of NIDDM. RESEARCH DESIGN AND METHODS: Studies published between January 1966 and January 1991 were identified through a computerized Medline search and by hand searching the bibliographies of identified articles. We identified 17 eligible randomized, controlled trials of combination therapy in NIDDM. These trials had a minimum duration of 8 wk and at least one of three outcome measures (fasting glucose, HbA1, or C-peptide) with SD or SE of the mean reported to do metaanalysis. With standardized forms, three independent reviews abstracted measures of study quality and specific descriptive information about population, intervention, and outcome measurements. RESULTS: We calculated effect size and weighted mean changes of the three outcome measures for control and treatment groups. In the treatment group, the fasting plasma glucose decreased from a mean of 11.4 mM (206 mg/dl) at baseline to a mean of 9.16 mM (165 mg/dl) posttreatment, whereas the control group decreased from (11.3 to 10.8 mM) (204 to 194 mg/dl) (effect size 0.39, P less than 0.0001). For HbA1, the treatment group decreased from a baseline of 11.0 to 10.2% compared to 11.0 and 11.2% in the control group (effect size 0.43, P less than 0.0001). For fasting C-peptide, the treatment group increased from 0.49 to 0.58 nM (1.45 to 1.75 ng/ml) compared with 0.47 and 0.43 (1.42 and 1.30) for the control group (effect size 0.26, P less than 0.017). CONCLUSION: Combined insulin-sulfonylurea therapy leads to modest improvement in glycemic control compared with insulin therapy alone. With combined therapy, lower insulin doses may be used to achieve similar control. Obese patients with higher fasting C-peptides may be more likely to respond than others.

Blood Glucose

Effects of hypoxemia at sea level and high altitude on sodium excretion and hormonal levels.

Acute hypoxemia at sea level is associated with decreased aldosterone secretion. This inhibition is thought to be mediated through secretion of atrial natriuretic factor (ANF). The interaction of these two hormones should result in enhanced renal salt excretion during hypoxemic conditions. This hypothesis was tested by administration of a standardized salt load to seven normal subjects during normoxemia at sea level (SL), acute hypoxemia (AH) at sea level, and high altitude (HA) (3,000 m). Urine and venous blood samples were collected and analyzed. A natriuresis and diuresis was observed only under AH conditions. It was accompanied by a decrease in plasma aldosterone levels, but did not correlate with changes in plasma aldosterone levels, ANF, or other hormones. Increased plasma renin activity (PRA) and increased norepinephrine levels were encountered at HA, suggesting sympathetic nervous system activation. No change in anti-diuretic hormone (ADH) levels with increased plasma osmolality was seen at HA. We conclude that excretion of a salt load during normobaric hypoxemia is enhanced by a decrease in plasma aldosterone levels, unrelated to changes in ANF or other hormones. The differences observed in norepinephrine, PRA, and ADH levels during HA versus AH conditions suggest that hypobaria or chronic hypoxemia may influence these hormonal responses.

Acute Disease

Blood types in cattle of Iberian ancestry and in Holsteins at various altitudes.

Gene frequencies of RBC antigens were determined in Holsteins and Colombian (criollas) cattle living at 3,000 m, and in cattle descended from fighting bulls (Vacas de lidia) living at 2,500 m. These frequencies were compared with those of Holsteins, cattle native to Florida (scrub cattle), longhorns, and native cattle from Brazil (caracu cattle) living at sea level. The criollas, Vacas de lidia, scrub cows, longhorns, and caracu are descendants of original Iberian stock introduced to the Americas. We found that despite common ancestry (scrub cattle, long-horns, criollas, and caracu), genetic differences may have been derived through years of demographic isolation. The most remarkable blood-group differences were found in the high prevalence of the B system phenogroup (heritable group of antigenic factors) BQA'G'34 in the Vacas de lidia, and of the S system phenogroup U1H' in these cattle and in caracu. Furthermore, the gene frequencies differed in the Holsteins maintained at moderately high altitude (descended from Holsteins kept at sea level), and may have been reflective of the need to adapt to moderately high altitude and chronic hypoxemic conditions. Blood group polymorphism was found in all groups of cattle, although it was reduced in the Vacas de lidia, possibly because their breeding has been carefully controlled and they appear to be highly inbred.

Altitude

Blood biochemical characteristics of cattle at sea level and at moderately high altitude (3,000 m).

We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas.

Altitude

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

Adult

Combination chemotherapy for soft-tissue sarcomas: a phase III study.

A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment 1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment 2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment 3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment 4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment 4. Responses were as follows: 1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%). 3 - NC 13/25 (52%). 4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment 4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in 1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H = 14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for 1 and 2, and 5 weeks for 3 and 4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.

Antineoplastic Agents

Travelers' diarrhea among U.S. Army troops in South Korea.

A prospective study of diarrhea was conducted among 98 U.S. Army soldiers during their first six weeks in South Korea. Diarrhea developed in 54 (55%) of 98 soldiers and had a mean duration of five days. Infections with Salmonella, Shigella, Vibrio, enterotoxigenic Escherichia coli, enteroviruses, and intestinal parasites were uncommon. Four (8%) of 50 soldiers with documented diarrhea, two (6%) or 32 with a history of diarrhea, and one (3%) of 29 who denied gastrointestinal symptoms had serologic evidence of a recent rotavirus infection. The etiology of diarrhea among U.S. soldiers who had recently arrived in South Korea differed from the etiology among travelers in warmer climates, where enterotoxigenic strains of E. coli were responsible for the majority of cases. Further efforts are needed to define other enteric pathogens in the etiology of diarrhea among new arrivals in different parts of the world.

Diarrhea

Treatment of carcinoma of base of tongue with radiation therapy and 5-fluorouracil. Potential for optimization with 18F-FU.

The treatment of advanced base of tongue carcinoma with concurrent radiation therapy and 5-fluorouracil versus radiation therapy alone is compared. Although the results are inconclusive, it is noteworthy that all the 5-year survivors were patients given combined treatment. Important questions regarding optimization of time-dose relationships with combined therapy were generated. Accordingly, 18F-5 fluorouracil was synthesized in an attempt to answer some of these questions.

Carcinoma, Squamous Cell

Carcinoma of the penis: analysis of 192 consecutive cases at the Instituto Nacional de Enfermedades Neoplasicas.

Between 1952 and 1976 192 consecutive cases of penile epidermoid carcinoma were seen at the Instituto Nacional de Enfermedades Neoplascias of Lima, Peru. The mean age when the disease developed was 60.5 years, with a peak incidence between 60 and 64 years (32 patients). No correlation was observed between extensive lesions of the shaft of the penis to high pathological staging. Clinical examination of the inguino-crural nodes is not a good criterion for staging. We wait six weeks after eradication of primary lesion before lymphadenectomy. No correlation exists between grade and pathological stage. When no lymph node was positive, the overall survival rate over five years was 90.69%; when lymph nodes were metastasized there was an overall survival rate over five years of only 9.39 percent. The coefficient of cancer versus noncancer cause of death was 1.25 for pathological stage I, 3.09 for pathological stage II, 4.83 for pathological stage III, and 10.000 for pathological stage IV. Our patients did have advanced disease, as 57.14% of deaths occurred at two years and 25.21% more at five years.

Adult

Serum C-peptide in renal failure patients following stimulation of pancreatic secretion.

We have demonstrated persistently elevated serum C-peptide concentrations in patients with chronic renal failure on chronic hemodialysis. A blunted serum C-peptide response to intravenous glucose, glucagon and tolbutamide was also found. However, the response to oral glucose stimulation was greater and more prolonged than in control subjects, probably related to the magnitude of hyperglycemia found in patients with chronic renal failure. These observations suggest the existence of a defect in the renal clearance of C-peptide although an abnormality in C-peptide secretion cannot be excluded.

Adult

Synovial sarcoma of the neck associated with previous head and neck radiation therapy.

Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.

Acne Vulgaris

Hemangiopericytoma of the uterus: report of a case with a comprehensive review of the literature.

A case of locally recurrent and metastatic uterine hemangiopericytoma successfully treated with surgery, radiotherapy and chemotherapy is presented. The patient is alive without evidence of detectable tumor, 13 years after the initial diagnosis. Review of the literature revealed 64 reported cases of uterine hemangiopericytoma. The clinical features are not sufficiently characteristic to enable the diagnosis to be made preoperatively. However, with the help of histological and ultrastructural studies a definite diagnosis of hemangiopericytoma can be made. The primary treatment is radical surgery which usually involved total hysterectomy and bilateral salpingo-oophorectomy. The prognosis of uterine hemangiopericytoma is better than that of other sites. However, long follow-up of these patients is necessary because of the tendency to local and distant recurrence many years after the initial treatment. The recurrent tumor should be treated aggressively with surgery, radiotherapy, and chemotherapy as long-term survival is not unusual.

Adult

Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.

Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

Alkylating Agents

Abnormalities in the regulation of growth hormone in chronic renal failure.

Carbohydrate intolerance is a common abnormality in patients with chronic renal failure. In this group of patients we investigated the interrelation among glucose, insulin, and growth hormone and confirmed the presence of carbohydrate intolerance and hyperinsulinemia. In addition we demonstrated alterations in growth hormone regulation, characterized by (1) the lack of suppression of growth hormone by orally induced hyperglycemia and paradoxical increase in serum levels of growth hormone after the administration of intravenous glucose or glucagon; (2) lack of release of growth hormone with induced hypoglycemia and an exaggerated response to levodopa administration. Furthermore, thyrotrophin-releasing hormone stimulated growth hormone release, a phenomenon not observed in the control population. Our studies show an impaired hypothalamic regulation of growth hormones secretion in patients with renal failure undergoing long-term hemodialysis.

Adult

Cholesterol embolization: a complication of angiography.

Cholesterol embolization is not widely recognized as a complication of major arteriographic procedures. In a retrospective study of 71 autopsies of patients who underwent diagnostic arteriographic procedures (20 with aortograms, 51 with cardiac catheterization and coronary angiography), we found an incidence of cholesterol embolization of 30% and 25.5%, respectively, in comparison with 4.3% in an age and disease-matched control population. The organs most frequently affected are the kidney and spleen following aortogram, and the myocardium following cardiac catheterization. The clinical importance of these findings cannot be ascertained from this study, but our experience with a single case demonstrates that radiographic studies may produce substantial morbidity.

Adult