Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.

BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis. CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT. RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI. CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.

Measuring 3D pyroelectric distributions with high resolution in thin films by a laser scanning microscope.

A laser scanning microscope for measuring 3D pyroelectric distributions inside thin vinylidene fluoride-trifluoroethylene copolymer films using the Laser Intensity Modulation Method was developed. The setup consists of a laser unit, a laser driver, an xyz-stepper motor unit, a transimpedance amplifier, and a lock-in amplifier. The focus lens at the laser unit is fixed by magnetic levitation and can correct a defocusing of the system or a tilt of the sample surface. It has been demonstrated in different samples that the system has a lateral resolution of 1 µm for measuring the topological surface structure or the pyroelectric distributions. The self-developed laser driver and transimpedance amplifier combined with a fast lock-in amplifier are able to measure small pyroelectric currents and their variation inside a pyroelectric sample in the range of some 1 pA. The maximum measure frequency of 4 MHz and the fast lock-in make it possible to measure the 3D pyroelectric distributions with high resolution. A 3D scan of 30 different layers with depths of 100 nm-5 µm inside the sample and 100 × 100 points in the xy-direction per layer is performed in 3 days.

Materials: carbon nanotubes in an ancient Damascus sabre.

The steel of Damascus blades, which were first encountered by the Crusaders when fighting against Muslims, had features not found in European steels--a characteristic wavy banding pattern known as damask, extraordinary mechanical properties, and an exceptionally sharp cutting edge. Here we use high-resolution transmission electron microscopy to examine a sample of Damascus sabre steel from the seventeenth century and find that it contains carbon nanotubes as well as cementite nanowires. This microstructure may offer insight into the beautiful banding pattern of the ultrahigh-carbon steel created from an ancient recipe that was lost long ago.

Negative muscle pennation angle as a sign of massive musculotendinous retraction after tendon tear: paradoxical function of the vastus lateralis muscle.

CASE REPORT: In the presented case, an isolated vastus lateralis tendon tear resulted in a negative pennation angle of the distal muscle fibers acting paradoxical to the physiological direction of the proximal muscle fibers. This observation makes the value of an in situ repair of a far retracted tendon tear with interposition of a graft questionable and emphasizes early over late anatomic surgical restoration of the muscle architecture after tendon tears.

Structure variations within RSi2 and R2TSi3 silicides. Part I. Structure overview.

Here, structural parameters of various structure reports on RSi2 and R2TSi3 compounds [where R is an alkaline earth metal, a rare earth metal (i.e. an element of the Sc group or a lathanide), or an actinide and T is a transition metal] are summarized. The parameters comprising composition, lattice parameters a and c, ratio c/a, formula unit per unit cell and structure type are tabulated. The relationships between the underlying structure types are presented within a group-subgroup scheme (Bärnighausen diagram). Additionally, unexpectedly missing compounds within the R2TSi3 compounds were examined with density functional theory and compounds that are promising candidates for synthesis are listed. Furthermore, a correlation was detected between the orthorhombic AlB2-like lattices of, for example, Ca2AgSi3 and the divalence of R and the monovalence of T. Finally, a potential tetragonal structure with ordered Si/T sites is proposed.

Structure variations within RSi2 and R2Si3 silicides. Part II. Structure driving factors.

To gain an overview of the various structure reports on RSi2 and R2TSi3 compounds (R is a member of the Sc group, an alkaline earth, lanthanide or actinide metal, T is a transition metal), compositions, lattice parameters a and c, ratios c/a, formula units per unit cell, and structure types are summarized in extensive tables and the variations of these properties when varying the R or T elements are analyzed. Following the structural systematization given in Part I, Part II focuses on revealing the driving factors for certain structure types, in particular, the electronic structure. Here, concepts of different complexity are presented, including molecular orbital theory, the principle of hard and soft acids and bases, and a Bader analysis based on Density Functional Theory calculations for representatives of the reported structure types. The potential Si/T ordering in different structures is discussed. Additionally, the influences from intrinsic and extrinsic properties (e.g. elemental size and electronics as well as lattice parameters and structure type) are investigated on each other using correlation plots. Thermal treatment is identified as an important factor for the ordering of Si/T atoms.

The lever arm ratio of the rotator cuff to deltoid muscle explains and predicts pseudoparalysis of the shoulder: the Shoulder Abduction Moment index.

AIMS: In patients with a rotator cuff tear, tear pattern and tendon involvement are known risk factors for the development of pseudoparalysis of the shoulder. It remains unclear, however, why similar tears often have very different functional consequences. The present study hypothesizes that individual shoulder anatomy, specifically the moment arms (MAs) of the rotator cuff (RC) and the deltoid muscle, as well as their relative recruitment during shoulder abduction, plays a central role in pseudoparalysis. MATERIALS AND METHODS: Biomechanical and clinical analyses of the pseudoparalytic shoulder were conducted based on the ratio of the RC/deltoid MAs, which were used to define a novel anatomical descriptor called the Shoulder Abduction Moment (SAM) index. The SAM index is the ratio of the radii of two concentric spheres based on the centre of rotation of the joint. One sphere captures the humeral head (numerator) and the other the deltoid origin of the acromion (denominator). A computational rigid body simulation was used to establish the functional link between the SAM index and a potential predisposition for pseudoparalysis. A retrospective radiological validation study based on these measures was also undertaken using two cohorts with and without pseudoparalysis and massive RC tears. RESULTS: Decreased RC activity and improved glenohumeral stability was predicted by simulations of SAM indices with larger diameters of the humeral head, being consequently beneficial for joint stability. Clinical investigation of the SAM index showed significant risk of pseudoparalysis in patients with massive tears and a SAM < 0.77 (odds ratio (OR) 11). CONCLUSION: The SAM index, which represents individual biomechanical characteristics of shoulder morphology, plays a determinant role in the presence or absence of pseudoparalysis in shoulders with massive RC tears.

Are commercially-available precontoured anatomical clavicle plating systems offering the purported superior optimum fitting to the clavicle? A cadaveric analysis and review of literature.

PURPOSE: The indication for operative treatment of displaced midshaft clavicle fractures remains controversial. However, if plate fixation is considered, implant prominence and skin irritation are the most common causes for re-operation. Low profile implants as well as closely contouring plates to the individual anatomy may reduce these complications. The aim of this study was to compare the fitting accuracy and implant prominence of 3.5mm pelvic reconstruction plates (PRP) with pre-contoured anatomical clavicle plates (PACP) for midshaft clavicle fractures. METHODS: Three-dimensional data of the largest, median and smallest male and female clavicle of an existing database of 89 cadaveric clavicles were included for analysis. A three-dimensional model of a commercially available PACP was used for digitally positioning of the plate on the segmented clavicles. Three-dimensional printouts of each clavicle were produced and the 3.5mm reconstruction plates were manually bent and positioned by the senior author. Computed tomography scans and three-dimensional reconstructions were then obtained to digitally compare the fitting accuracy and implant prominence. RESULTS: Pelvic reconstruction plates offered superior fitting accuracy and lower implant prominence compared to PACP. The largest difference in implant prominence was observed in large sized female clavicles and measured 3.6mm. CONCLUSION: Both, the less costly PRP plates and commercially available PACP for midshaft fractures of the clavicle demonstrated a clinically acceptable fitting accuracy. The manually bent pelvic-reconstruction plates demonstrated reduced implant prominence with superior fitting. Hypothetically this might contribute to a reduced rate of reoperation. LEVEL OF EVIDENCE: Level IV cadaveric study.

Tendon retracts more than muscle in experimental chronic tears of the rotator cuff.

We released the infraspinatus tendons of six sheep, allowed retraction of the musculotendinous unit over a period of 40 weeks and then performed a repair. We studied retraction of the musculotendinous unit 35 weeks later using CT, MRI and macroscopic dissection. The tendon was retracted by a mean of 4.7 cm (3.8 to 5.1) 40 weeks after release and remained at a mean of 4.2 cm (3.3 to 4.7) 35 weeks after the repair. Retraction of the muscle was only a mean of 2.7 cm (2.0 to 3.3) and 1.7 cm (1.1 to 2.2) respectively at these two points. Thus, the musculotendinous junction had shifted distally by a mean of 2.5 cm (2.0 to 2.8) relative to the tendon. Sheep muscle showed an ability to compensate for approximately 60% of the tendon retraction in a hitherto unknown fashion. Such retraction may not be a quantitatively reliable indicator of retraction of the muscle and may overestimate the need for elongation of the musculotendinous unit during repair.

A new methodology for the planning of single-cut corrective osteotomies of mal-aligned long bones.

BACKGROUND: Corrections of combined torsional and angular deformities of long bones may be performed creating a single osteotomy which is oriented so that rotating the two fragments on the created osteotomy plane allows to correct all deformities in one step. A practical geometrical tool is presented to facilitate the difficult preoperative planning of such osteotomies. METHODS: The geometrical tool consists of two limbs connected by a mobile disk representing the osteotomy plane. This allows the two limbs to be deliberately bent and rotated against each other. Thereby, the mobile disk will change orientation in such a way that it will indicate the osteotomy plane needed in order to anatomically align the two limbs. The geometrical principle of the tool has been confirmed mathematically and compared with data from the literature. Five deformed test bones have been used to test the effectiveness of the tool. FINDING: . The geometrical principle of the tool is equivalent with the mathematical data from the literature. The maximal osteotomy angle which can be indicated by the tool is 65 degrees , with an error of +/-3 degrees compared to mathematically calculated values. The five test bones were all aligned anatomically with appropriate accuracy. INTERPRETATION: The presented tool can be easily used and facilitates largely the preoperative planning of a single cut osteotomy for complex deformities of long bones. It allows to avoid sophisticated mathematical calculations and helps to avoid the risk for errors in planning and performing correctional osteotomies.

Hypothalamic and raphe serotonergic systems in ovulation control.

The role of hypothalamic and midbrain serotonergic systems in the control of ovulation in the rat has been investigated using 5,7-dihydroxytryptamine (5,7-DHT) lesioning in conjunction with desmethylimipramine pretreatment. Intracisternal injection of 5,7-DHT (100 or 200 microgram) produced a dose-dependent decrease in the incidence of ovulation induced by PMS gonadotrophin (PMSG; 8 IU sc on day 30). Intraventricular injection of 200 microgram 5.7-DHT via the lateral ventricles completely blocked PMSG-induced ovulation. After injection into either site, nonovulatory animals were in proestrus on day 33 and contained fluid-filled uteri. Intracerebral injection of 5,7-DHT into the dorsal or median raphe significantly decreased the numbers of animals induced to ovulate. The extent and specificity of these chemical lesions were evaluated in the suprachiasmatic (SNR) and arcuate-median eminence regions of PMSG-treated rats using an in vitro uptake model. A general feature of every case of inhibited ovulation was the significant decrease in uptake of serotonin in the SNR, indicating destruction of serotonergic inputs to this region. This suggests that serotonergic SNR input from the dorsal raphe region is essential to ovulation. Median raphe lesions appeared to be more extensive than dorsal raphe lesions, involving serotonergic projections to the arcuate-median eminence region. In addition, ascending noradrenergic projections to the SNR were significantly destroyed, also implicating these systems in ovulation control.

Hypothalamic and suprachiasmatic uptake of serotonin in vitro: twenty-four-hour changes in male and proestrous female rats.

Twenty-four-hour changes in the in vitro serotonin (5-HT) uptake capacity of hypothalamic homogenates and of "Vibratome" slices of the suprachiasmatic nuclear region (SNR) of the hypothalamus were studied in 60-90-day-old Holtzman (albino) rats. Animals acclimated to artificially illuminated (fluorescent, LD 12:12) and temperature controlled (22 +/- 2 C) rooms were killed 6% each of 8 time points. Synaptosomal fractions from homogenates of whole hypothalamus, and slices of the SNR were incubated for 20 min in Krebs-Henseleit buffer with [3H]5-HT. Males showed a single daily peak in SNR uptake at the start of darkness, and a minimum near the onset of light, while a more complex pattern containing 3 peaks and minima occurred in uptake by hypothalamic homogenates. Proestrous females showed a single high amplitude peak SNR uptake during the critical period, just prior to the plasma LH peak determined in the same animals by radioimmunoassay. It is suggested that this short-term and 4-fold increase in SNR uptake of 5-HT may serve to limit free 5-HT and its inhibitory or other effects on the gonadotropin release hormone system and thereby on LH release and ovulation.

GABA control of LHRH release is dependent on the steroid milieu.

The effect of GABA in controlling luteinizing hormone releasing hormone (LHRH) release from isolated hypothalamic fragments containing the mediobasal hypothalamus, suprachiasmatic nucleus, and the preoptic area (MBH-SCN-POA) was tested under different hormonal conditions with an in vitro superfusion method. GABA significantly decreased LHRH release under conditions of low, chronic levels of estradiol (E2) treatment but had no effect on tissue obtained from animals in proestrus. This suggests that the inhibitory effect of GABA is only manifested during certain stages of the estrous cycle characterized by negative feedback and low E2.

Serotonin stimulation of the period of in vitro LHRH release is estradiol dependent.

The neurotransmitter serotonin (5-HT) has well known effects on the release of luteinizing hormone (LH) which may be estrogen and photoperiod dependent. An in vitro superfusion system was used to assess the potential role of 5-HT and photoperiod in modulating the release of luteinizing hormone releasing hormone (LHRH) from the mediobasal-suprachiasmatic-preoptic area (MBH-POA-SCN) in the ovariectomized (OVX) and OVX estradiol (E2) implanted rat model of LH release. Regularly cycling female Holtzman strain rats, maintained on a photoperiod of 0500-1900 or 0100-1500 hr light were OVX, and silastic capsules containing estradiol-17 beta (150 micrograms/ml) or sesame oil implanted SC. Two days later the rats were killed at 1000 hr and the MBH-POA-SCN isolated. Tissue was superfused in vitro with Krebs-Ringer-Phosphate buffer (KRP) for 2 hours followed by 3 hours of KRP with intermittent superfusion of 5-HT at increasing concentrations: 1 X 10(-10) M (1st hour); 1 X 10(-8) (2nd hour); 1 X 10(-6) M (3rd hour). Superfusate was collected every 10 min for the entire 5 hour incubation period and LHRH measured by RIA with the following results. In the OVX rat 5-HT significantly (p less than 0.05) increased the period of LHRH pulses and decreased the release of LHRH compared to control superfusions, while in the OVX E2 rat 5-HT significantly (p less than 0.05) decreased the period of LHRH release and increased the release of LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of endogenous serotonin in phasic LH release.

Injection of the serotonin inhibitor, fluoxetine (75 micrograms) into the hypothalamus (IC) of ovariectomized (Ovx.) rats treated with 17beta-Estradiol (E2) and parachlorophenylalanine (PCPA 150 mg/kg) significantly increased the luteinizing hormone (LH) in these rats 24 hours later when PCPA had suppressed the LH surge in a parallel group of sham rats. There was a temporal delay in these changes of LH (and by implication serotonin metabolism), since there was no significant effect on the blocked LH surge within two hours of the injection. Since steroids play a major role in gonadotropin secretion and PCPA has been shown to depress LH release, it is interesting that E2 increased the rate of H-3 serotonin (1 X 10(-7) M) uptake in hypothalamic synaptosomes. This suggests a mechanism to increase the removal of synaptic serotonin and the low concentrations of serotonin used in these experiments suggest that uptake occurred in the high affinity serotonin uptake pump and can be influenced by ovarian steroids. This is in contrast to the saturation uptake of serotonin which was unaffected by steroids.

Role of 5-hydroxytryptamine receptors on luteinizing-hormone-releasing hormone release in the ovariectomized, estradiol-treated rat.

The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5-HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) treated rats using in vitro superfusion techniques. Regularly cycling female Holtzman rats (250-300 g) were maintained on a photoperiod of 0500-1900 h light at 22 +/- 2 degrees C. Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150 micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2 receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist Lilly 53857 (1 x 10(-6) M or 1 x 10(-5) M) did not increase LHRH release above control levels. Neither 5-HT nor quipazine had a significant effect on LHRH release at 1 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(-5) M) significantly (p less than 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT1 receptor plays a role in LHRH release and this effect may be related to the opposing effects of postsynaptic and autoreceptors. However, the failure of Lilly 53857 to reproduce the stimulatory effect of ketanserin on LHRH release suggests that 5-HT2 receptors in the MBH-POA-SCN may not modify LH release during the estrous cycle.

Uptake of serotonin and norepinephrine in hypothalamic and limbic brain regions during the estrous cycle and the effect of neurotoxin lesions on estrous cyclicity.

The temporal pattern of hypothalamic and limbic aminergic activity during the estrous cycle has been measured by changes in the serotonergic and noradrenergic neuronal uptake during the regular estrous cycle. Significant changes (p = 0.006, 0.01) in the uptake of 3H 5-HT and 3H NE were recorded in the suprachiasmatic nuclei (SCN) at 1200 hours on proestrus. Significant changes (p = 0.01, 0.018) in the uptake of 3H 5-HT in the preoptic area (POA) were found at 1200 hours on both diestrus and proestrus while median eminence (ME) 5-HT showed a significant increase only during proestrus (p = 0.001). In the amygdala (AMYG) 3H 5-HT uptake was significantly different at 1200 hours on diestrus and proestrus while 3H NE uptake was significant (p = 0.001) at 1200 hours only during proestrus. The plasma proestrous luteinizing hormone surge occurred at 1700 hours. The serotonin neurotoxin, 5,7-dihydroxytryptamine, was stereotaxically injected through a 30 gauge needle in concentrations of 5-10 micrograms/microliters/minute for 1 minute in various nuclear regions. In the SCN 4 or 5 day estrous cyclicity was interrupted by diestrus for average periods of up to 15 days; in the POA for periods of 10 days; in the ME for periods of 13 days; and in the AMYG for periods of up to 6 days. Sham injections of 5% ascorbic acid had no effect on cyclicity and following these periods of acyclicity rats resumed normal cycles. These lesion effects and patterns of uptake suggest a common timing mechanism utilizing serotonergic raphe systems for neuroendocrine control. Lesions with 5,7-DHT in all four brain regions disrupt cyclicity, but the greatest delays occur in the SCN and ME regions which are particularly critical to intrinsic neuroendocrine rhythms. Patterns of increase in reuptake capacity in all 4 regions occur 3 hours prior to the critical period for the plasma LH surge and may be an important mechanism for many types of neuroendocrine events including ovulation.

Effect of tendon release and delayed repair on the structure of the muscles of the rotator cuff: an experimental study in sheep.

BACKGROUND: Ruptures of the tendons of the rotator cuff lead to profound and possibly irreversible changes in the structure and physiological properties of the rotator cuff muscles. Muscle atrophy and fatty infiltration are important prognostic factors that affect the natural history and outcome of treatment. The purpose of this study was to examine the amount of muscle atrophy and fatty infiltration in an animal model and to determine whether the repair of a long-standing tendon tear can reverse these changes. METHODS: The infraspinatus tendon in six sheep was released and encased in a silicone tube to prevent spontaneous healing. The musculotendinous unit was allowed to retract for forty weeks. Throughout this period, the muscular changes were studied with use of computed tomography, histological analysis, and electron microscopy. At forty weeks, the elasticity, intramuscular pressure, and perfusion were measured intraoperatively and a tendon repair was carried out. The structural changes of the muscle were studied for thirty-five weeks after the repair. The animals were then killed, and the musculotendinous units were examined macroscopically and by computed tomography, histological analysis, and electron microscopy. RESULTS: At the time of the tendon release, the infraspinatus showed no fatty changes. The force needed to cause a tendon excursion of 1 cm was a mean (and standard deviation) of 6.8 +/- 1 N. The application of tension on the tendon did not alter the perfusion and decreased the intramuscular pressure. After the tendon release, muscular atrophy developed and there was a significant increase (p < 0.001) in interfascicular and intrafascicular fat, representing fatty infiltration rather than fatty degeneration. Furthermore, there was an increase of interstitial connective tissue. At the time of the tendon repair, between forty and forty-two weeks after the release, there was a sevenfold poorer elasticity of the musculotendinous unit but preserved muscle perfusion. The structural changes increased six weeks after the repair and then recovered partially at twelve and thirty-five weeks thereafter but only to the amount demonstrated before the repair. CONCLUSIONS: Musculotendinous retraction induced by tendon release is associated with profound changes in the structure and function of the affected muscle. Vascularization, intramuscular pressure, and individual fiber composition are not markedly affected, and muscle fibers do not appear to degenerate. However, muscle atrophy, infiltration by fat cells, and an increase of interstitial connective tissue lead to impairment of the physiological properties of the muscle. These changes were irreversible under the conditions of this experiment with the repair technique used.

In vivo tendon force measurement of 2-week duration in sheep.

Tendon tension in vivo may be determined indirectly by measuring intratendinous pressure, by using a buckle transducer or by measuring the tendon strain. All of these methods require appropriate calibration, which is highly dependent on various variables. To measure the tendon load in vivo during a period of 2 weeks in sheep, a measurement technique has been developed using a force sensor interposed serially between the humeral head and the tendon end. Within a supporting frame, a flexion-sensitive force transducer is subjected to three-point bending stress. The load is transmitted by sutures from the tendon end through a hole in the sensor frame, orthogonal to the force transducer. In this configuration, the sensor measures the tensile force acting on the tendon, largely independent of the loading direction. The sensor was screwed to the humeral head and connected to the tendon end which was previously released from its insertion site along with a bone chip, using sutures. Connecting wires passed subcutaneously to a skin outlet about 30 cm away from the transducer. The sensor output was linear to the measured load up to 300 N, with maximum hysteresis of 18% full scale. All sensors worked in vivo without drift over a period of up to 14 days with no change in the calibration data. Forces up to 310 N have been recorded in vivo with daily tension measurements. This study shows that serial tendon tension measurement is feasible and allows for reliable, repeatable recording of the absolute tendon tension at the expense of tendon integrity.

The effects of perinatal exposure to nicotine on plasma LH levels in prepubertal rats.

Adult female rats were chronically treated with nicotine administered via the drinking water during pregnancy and/or lactation. The approximate doses of nicotine consumed per day were 2.4 mg/kg and 4.5 mg/kg of body weight. The pups were weaned at 20 days of age. The pups were killed by decapitation on postnatal days 20, 30, or 40 and plasma from heparinized trunk blood was assayed for luteinizing hormone (LH). At 30 days of age untreated male and female offspring had the highest levels of plasma LH compared to 20 and 40 days of age. This level was not affected by any subsequent dose or treatment. Prepubertal females exposed to nicotine during pregnancy failed to exhibit the pattern of LH levels seen in control animals, whereas those exposed during lactation or throughout the perinatal period showed a distinctive pattern of plasma LH. Chronic exposure of female offspring to the low dose of nicotine during lactation tended to increase plasma LH levels at 20 and 40 days. Female offspring exposed to nicotine during pregnancy or to the low dose during lactation showed significant deficits in body weight at 40 days of age which appeared to correlate with a delay in vaginal opening. The results suggest that perinatal exposure to maternally administered nicotine may disrupt normal patterns of LH release in the offspring of both sexes and alter sexual development in female offspring.