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Biomedical subjects

M S Shapiro

Publications and source records attributed to M S Shapiro.

At least 19 recordsLinked to original sources
PubMed1992

Identification and preliminary characterization of two human digitalis-like substances that are structurally related to digoxin and ouabain.

In order to characterize the structure of endogenous digitalis-like immunoreactive factor (DLIF), we utilized peritoneal dialysis fluid from patients with chronic renal failure as a source of endogenous digitalis-like immunoreactive factor (DLIF), and subjected it to one-step ion exchange chromatography, followed by one step reverse HPLC. Crude dialysis fluid contained 0.09 ng/ml of DLIF, and using Amberlite XAD-2 chromatography we extracted 110 ng of DLIF from 800 ml of dialysis fluid. By applying this partially purified DLIF to our HPLC system, we discerned three peaks of DLIF activity, with retention times of 34, 58 and 63 minutes. The first peak overlapped the elution profile of ouabain, and the third peak co-eluted precisely with digoxin. The second DLIF peak was not in proximity to any of the digitalis-like markers employed. Thus, our results indicate that DLIF isolated from peritoneal dialysis fluid exists in three distinct forms, one of which resembles ouabain, and one which is identical to digoxin.

Digoxin↗
PubMed1992

Polyglandular autoimmune syndrome type I among Iranian Jews.

Polyglandular autoimmune syndrome (PAS) has been well characterised and the accepted criteria for diagnosis are the presence of at least two of the three major components: hypoparathyroidism (HPT), candidiasis, and adrenal insufficiency (AI). HPT may, however, be the only manifestation of the syndrome. Iranian Jews, having a high rate of consanguinity, appear to be a community in which PAS type I is frequent. We report on 19 families of patients with HPT from the Iranian Jewish community assuming that they are in fact affected with PAS type I. In the 19 families, 23 patients were affected, including 11 males and 12 females. All the patients but one had HPT (96%), and most were diagnosed by the age of 20 years (91%). AI was diagnosed in five of our patients; in all cases but one it appeared after HPT. Mild oral candidiasis was present in four patients and six of the patients (three males and three females) had hypogonadism. Other features of the syndrome found in some of our patients were pernicious anaemia, hypothyroidism, and alopecia. The disease is autosomal recessive and the calculated prevalence among the Iranian Jews is 1:6500 to 1:9000. The disease is also found with a very high incidence among Finns. A comparison of the symptoms between the two groups showed clinical differences including the relative rarity of candidiasis and absence of keratopathy among the Iranian Jews.

Adolescent↗
PubMed1991

Selectivity and gating of the type L potassium channel in mouse lymphocytes.

Type l voltage-gated K+ channels in murine lymphocytes were studied under voltage clamp in cell-attached patches and in the whole-cell configuration. The kinetics of activation of whole-cell currents during depolarizing pulses could be fit by a single exponential after an initial delay. Deactivation upon repolarization of both macroscopic and microscopic currents was mono-exponential, except in Rb-Ringer or Cs-Ringer solution in which tail currents often displayed "hooks," wherein the current first increased or remained constant before decaying. In some cells type l currents were contaminated by a small component due to type n K+ channels, which deactivate approximately 10 times slower than type l channels. Both macroscopic and single channel currents could be dissected either kinetically or pharmacologically into these two K+ channel types. The ionic selectivity and conductance of type l channels were studied by varying the internal and external permeant ion. With 160 mM K+ in the cell, the relative permeability calculated from the reversal potential with the Goldman-Hodgkin-Katz equation was K+ (identical to 1.0) greater than Rb+ (0.76) greater than NH4+ = Cs+ (0.12) much greater than Na+ (less than 0.004). Measured 30 mV negative to the reversal potential, the relative conductance sequence was quite different: NH4+ (1.5) greater than K+ (identical to 1.0) greater than Rb+ (0.5) greater than Cs+ (0.06) much greater than Na+, Li+, TMA+ (unmeasurable). Single channel current rectification resembled that of the whole-cell instantaneous I-V relation. Anomalous mole-fraction dependence of the relative permeability PNH4/PK was observed in NH4(+)-K+ mixtures, indicating that the type l K+ channel is a multi-ion pore. Compared with other K+ channels, lymphocyte type l K+ channels are most similar to "g12" channels in myelinated nerve.

Ammonia↗
PubMed1991

Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes.

Permeant ion species was found to profoundly affect the gating kinetics of type l K+ currents in mouse T lymphocytes studied with the whole-cell or on-cell patch gigaohm-seal techniques. Replacing external K+ with Rb+ (as the sole monovalent cation, at 160 mM) shifted the peak conductance voltage (g-V) relation by approximately 20 mV to more negative potentials, while NH4+ shifted the g-V curve by 15 mV to more positive potentials. Deactivation (the tail current time constant, tau tail) was slowed by an average of 14-fold at -70 mV in external Rb+, by approximately 8-fold in Cs+, and by a factor of two to three in NH4+. Changing the external K+ concentration, [K+]o, from 4.5 to 160 mM or [Rb+]o from 10 to 160 mM had no effect on tau tail. With all the internal K+ replaced by Rb+ or Cs+ and either isotonic Rb+ or K+ in the bath, tau tail was indistinguishable from that with K+ in the cell. With the exception of NH4+, activation time constants were insensitive to permeant ion species. These results indicate that external permeant ions have stronger effects than internal permeant ions, suggesting an external modulatory site that influences K+ channel gating. However, in bi-ionic experiments with reduced external permeant ion concentrations, tau tail was sensitive to the direction of current flow, indicating that the modulatory site is either within the permeation pathway or in the outer vestibule of the channel. The latter interpretation implies that outward current through an open type l K+ channel significantly alters local ion concentrations at the modulatory site in the outer vestibule, and consequently at the mouth of the channel. Experiments with mixtures of K+ and Rb+ in the external solution reveal that deactivation kinetics are minimally affected by addition of Rb+ until the Rb+ mole fraction approaches unity. This relationship between mole fraction and tau tail, together with the concentration independence of tau tail, was hard to reconcile with simple models in which occupancy of a site within the permeation pathway prevents channel closing, but is consistent with a model in which a permeant ion binding site in the outer vestibule modulates gating depending on the species of ion occupying the site. A description of the ionic selectivity of the type l K+ channel is presented in the companion paper (Shapiro and DeCoursey, 1991b).

Ammonia↗
PubMed1991

Variable hormonogenesis in Cushing's syndrome.

Four patients with Cushing's syndrome and variable cyclic hormonogenesis are reported and 40 other cases from the literature are reviewed. These cases were divided into four categories depending on regular or irregular cyclic adrenal hypersecretion and presence or absence of concomitant fluctuations in the clinical course. The manifestations of cyclic adrenal hypersecretion in these patients varied from daily to yearly intervals. Cyclic activity persisted for as long as 25 years, with cycle lengths varying from 12 hours to 85 days. Some patients demonstrated complex biochemical cyclic patterns. Clinical presentations varied from a single outstanding symptom, such as recurring oedema, to a complex clinical syndrome. The aetiology in these patients varied: 12 appeared to be pituitary dependent, 11 had corticotropin-producing tumours and another eight were described as showing 'adrenal hyperplasia'. A hypothalamic disorder was found in four, a benign adrenal adenoma in two, and an adrenal 'mass' and adrenocortical nodular dysplasia in single patients. Evaluation during the intercyclic phase may reveal normal pituitary function. Inconsistent responsiveness to administration of dexamethasone in different phases of cyclic activities may suggest the presence of cyclic Cushing's syndrome.

Adrenocorticotropic Hormone↗
PubMed1991

The effect of section of the medial collateral ligament on force generated in the anterior cruciate ligament.

Ten fresh-frozen knees from cadavera were instrumented with a specially designed transducer that measures the force that the anterior cruciate ligament exerts on its tibial attachment. Specimens were subjected to tibial torque, anterior tibial force, and varus-valgus bending moment at selected angles of flexion of the knee ranging from 0 to 45 degrees. Section of the medial collateral ligament did not change the force generated in the anterior cruciate ligament by applied varus moment. When valgus moment was applied to the knee, force increased dramatically after section of the medial collateral ligament; the increases were greatest at 45 degrees of flexion. Section of the medial collateral ligament had variable effects on the force generated in the anterior cruciate ligament during internal rotation but dramatically increased that generated during external rotation; these increases were greatest at 45 degrees. Section of the medial collateral ligament increased mean total torsional laxity by 13 degrees (at 0 degrees of flexion) to 20 degrees (at 45 degrees of flexion). Application of an anteriorly directed force to the tibia of an intact knee increased the force generated in the anterior cruciate ligament; this increase was maximum near the mid-part of the range of tibial rotation and minimum with external rotation of the tibia. Section of the medial collateral ligament did not change the force generated in the anterior cruciate ligament by straight anterior tibial pull near the mid-part of the range of tibial rotation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Serum fructosamine assay in the evaluation and follow-up of diabetics].

Fructosamine (FRA) levels were determined in diabetic and nondiabetic patients. A normal mean of 2.38 mmol/L +/- 0.21 (SD), and range of 2.0-2.8, was found in 156 nondiabetic subjects. A highly significant correlation was found between FRA and glycosylated hemoglobin, and between FRA and fasting glucose and 2-hour postprandial glucose in the 163 diabetics. The mean FRA in 60 diabetics receiving oral hypoglycemic agents was 3.05 +/- 0.34. It ranged from 3.28 +/- 0.65 in patients with NIDDM receiving insulin to 3.50 +/- 1.03 in those with IDDM. Over 60% of the latter were inadequately controlled, as assessed by FRA levels. FRA repeated during 4-12 months in 68 patients showed no improvement in 45%, despite determined attempts to control blood glucose. However, fasting blood glucose in diabetics with normal FRA was 134 +/- 51 mg/dl. Therefore, a consistently normal level of FRA does not indicate normoglycemia. The FRA assay is rapid, simple, economical and of significant aid in the control of diabetes.

Blood Glucose↗
PubMed1990

Wrist loading patterns during pommel horse exercises.

Gymnastics is a sport which involves substantial periods of upper extremity support as well as frequent impacts to the wrist. Not surprisingly, wrist pain is a common finding in gymnasts. Of all events, the pommel horse is the most painful. In order to study the forces of wrist impact, a standard pommel horse was instrumented with a specially designed load cell to record the resultant force of the hand on the pommel during a series of basic skills performed by a group of seventeen elite male gymnasts. The highest mean peak forces were recorded during the front scissors and flair exercises (1.5 BW) with peaks of up to 2.0 BW for some gymnasts. The mean peak force for hip circles at the center or end of the horse was 1.1 BW. The mean overall loading rate (initial contact to first loading peak) ranged from 5.2 BWs-1 (hip circles) to 10.6 BW s-1 (flairs). However, many recordings displayed localized initial loading spikes which occurred during 'hard' landings on the pommel. When front scissors were performed in an aggressive manner, the initial loading spikes averaged 1.0 BW in magnitude (maximum 1.8 BW) with an average rise time of 8.2 ms; calculated localized loading rates averaged 129 BW s-1 (maximum 219 BW s-1). These loading parameters are comparable to those encountered at heel strike during running. These impact forces and loading rates are remarkably high for an upper extremity joint not normally exposed to weight-bearing loads, and may contribute to the pathogenesis of wrist injuries in gymnastics.

Adolescent↗
PubMed1990

Gadolinium-DTPA enhanced magnetic resonance imaging in acoustic neuroma diagnosis and management.

Gadolinium-DTPA (Gd-DTPA) is a paramagnetic contrast agent that increases the intensity of acoustic neuromas (AN) on T1-weighted magnetic resonance imaging (MRI) scans. Over a 9-month period we have reviewed Gd-DTPA-enhanced MRI scans on 32 consecutive cases (35 tumors) involving the internal auditory canal (IAC) and cerebellopontine angle (CPA). The majority of patients (84%) were imaged on latest generation 1.5 Tesla scanners. Every tumor studied showed marked enhancement after Gd-DTPA administration. This improved contrast permitted identification of three small tumors that were not evident on unenhanced scans. Gd-DTPA appears to be particularly useful in the evaluation of recurrent or residual AN. In three patients with known residual tumor after planned subtotal excisions, the remaining tumor could only be differentiated from surrounding scar, cerebral spinal fluid (CSF), and brain parenchyma after contrast enhancement. In one of these, a small rim of tumor capsule left on the facial nerve was evident only on Gd-DTPA-enhanced T1 images. Gd-DTPA also provides a more reliable estimate of the depth of tumor penetration in the IAC. This information is useful in selecting candidates suitable for a hearing conservation approach.

Contrast Media↗
PubMed1990

Direct measurement of resultant forces in the anterior cruciate ligament. An in vitro study performed with a new experimental technique.

A new technique was used to measure the resultant forces in the anterior cruciate ligament during a series of loading experiments on seventeen fresh-frozen cadaver specimens. The base of the ligament's tibial attachment was mechanically isolated with a coring cutter, and a specially designed load-transducer was fixed to the bone-plug that contained the ligament's tibial insertion so that the resultant forces were directly measured by the load-cell. Although the magnitudes of values for forces varied considerably between specimens for a given test condition, the patterns of loading with respect to direction of loading and the angle of flexion of the knee were remarkably consistent. Passive extension of the knee generated forces in the ligament only during the last 10 degrees of extension; at 5 degrees of hyperextension, the forces ranged from fifty to 240 newtons (mean, 118 newtons). When a 200-newton pull of the quadriceps tendon was applied to extend a knee slowly against tibial resistance, however, the force in the ligament increased at all angles of flexion of the knee. Internal tibial torque always generated greater forces in the ligament than did external tibial torque; higher forces were recorded as the knee was extended. The greatest forces (133 to 370 newtons) were generated when ten newton-meters of internal tibial torque was applied to a hyperextended knee. Fifteen newton-meters of applied varus moment generated forces of ninety-four to 177 newtons at full extension; fifteen newton-meters of applied valgus moment generated a mean force of fifty-six newtons, which remained unchanged with flexion of the knee. The force during straight anterior translation of the tibia was approximately equal to the anterior force applied to the tibia. The application of 925 newtons of tibiofemoral contact force reduced the mean force in the ligament that was generated by 200 newtons of anterior pull on the tibia by 36 per cent at full extension and 46 per cent at 20 degrees of flexion.

Aged↗
PubMed1989

Fractionation of urinary 17-ketosteroids by gas chromatography: a neglected procedure in the assessment of hyperandrogenicity in the hirsute female.

17-Ketosteroids were determined by gas chromatography in twenty four-hour urine samples from 62 hirsute females. The method permitted the determination of androsterone (A), aetiocholanolone (E) and dehydroepiandrosterone (D). Elevated concentrations of one or more of these metabolites were detected in 81% of the samples. Two main patterns of hyperandrogenicity were observed: 1) Hyper A + E (27%) and 2) Hyper A (26%). Elevated AD, AED, D, ED or E were less common, but in total these patterns comprised another 28%. The plasma testosterone and total urinary 17-ketosteroid concentrations were elevated in only 21% and 23% of the samples, respectively. Thirty two out of 33 patients with elevated urine metabolites showed significant suppression following dexamethasone administration (2 mg/day during 6 days). Thus, dexamethasone suppressable hyperandrogenicity was predominant in this group of hirsute females. Elevations of urinary androsterone and aetiocholanolone are probably contingent on the relative activities of 5 alpha- and 5 beta-reductases) in the presence of increased androstenedione secretion. Elevations of urinary dehydroepiandrosterone suggest decreased adrenal cortical 3 beta-hydroxysteroid dehydrogenase) activity. Thus, fractionation of urinary 17-ketosteroids seems to be an effective test in the evaluation of hirsutism.

17-Ketosteroids↗
PubMed1989

Neutrophil chemotaxis, random migration, and adherence in patients with hyperthyroidism.

We have examined neutrophil adherence, chemotactic activity, and random migration in 35 hyperthyroid patients with Graves' disease and 106 normal volunteers. No statistically significant differences were found between granulocyte adherence of 17 hyperthyroid subjects (67 +/- 15.6%) and 81 healthy volunteers (63.1 +/- 17%). In 3 thyrotoxic patients, impaired neutrophil adherence was found, which resolved when thyroid function returned to normal. The neutrophil chemotactic activity of 32 normal controls was 107.5 +/- 21.4 cells, and the random migration 36 +/- 15.5 cells. No statistically significant difference was demonstrated in 13 hyperthyroid patients who had a neutrophil chemotactic activity of 102 +/- 14.6 cells and a random migration of 31.2 +/- 13.2 cells. Defective chemotactic activity and random migration was found in 2 patients. Neutrophil functions returned to normal in one of the two subjects who were re-evaluated when thyroid function recovered. In summary, 14% of hyperthyroid patients had impaired leukocyte functions. However, severe pyogenic infections are quite rare in hyperthyroid patients, indicating that the observed alterations in function of phagocytic cells are not clinically important.

Cell Migration Inhibition↗
PubMed1989

Abnormal thyroid function in hyperemesis gravidarum.

Thyroid function was evaluated in 41 consecutive women with hyperemesis gravidarum (HG). In 11, increased free thyroxin concentrations (FT4) were measured. After one week of conservative therapy, 4 patients with persistent emesis were treated with antithyroid agents. Three of these 4 displayed other signs of hyperthyroidism. Emesis resolved in the other 7 patients within a week of conservative therapy. FT4 levels also returned to normal in these 7 patients within several weeks. Thyrotropin-releasing hormone (TRH) was administered to 10 of the 11 patients. Abnormal TSH responses, suggesting varying degrees of autonomous thyroid function were noted in all 4 patients treated with antithyroid drugs and in 3 of the untreated patients. Underlying clinical signs and symptoms of hyperthyroidism should be sought in patients with HG. In the presence of persistent emesis, despite conservative therapy of at least one week's duration and the presence of abnormal thyroid function studies, the use of antithyroid agents should be considered.

Adult↗
PubMed1989

Pulmonary manifestations of gastrointestinal disease.

The respiratory and gastrointestinal systems share several functional similarities. In health, the two systems remain structurally distinct and functionally integrated, so as to maintain physiologic homeostasis. However, in the setting of disease, pathophysiologic alterations in one system may be reflected in the other. This article focuses upon the nonmalignant gastrointestinal causes of respiratory illness. Using an anatomic approach, the pulmonary manifestations of selected gastrointestinal diseases are outlined. Emphasis is placed on the distinguishing features, pathophysiology, and therapy of the pulmonary sequelae of digestive diseases.

Esophageal Diseases↗