Proteinuria, hypertension and chronic renal failure in X-linked Kallmann's syndrome, a defined genetic cause of solitary functioning kidney.

Background: Anosmia and hypogonadotrophic hypogonadism are the classic features of X-linked Kallmann's syndrome, a disorder caused by mutations of KAL, a gene expressed during kidney and brain development. About a third of patients have a solitary functioning kidney, but little is known about their renal morbidity.

Methods: We studied seven patients aged 22-35 years with X-linked Kallmann's syndrome and a solitary functioning kidney.

Contrasting expression of KAL in cell-free systems: 5' UTR and coding region structural effects on translation.

We investigated the expression of two different X-linked Kallmann (KAL) gene cDNAs in two different cell-free systems using rabbit reticulocyte lysate: (system A) transcription/translation coupled and (system B) noncoupled. System A yielded a single band of 76 kDa corresponding to anosmin-1, the expected full-length gene product, and upon addition of canine microsomal membranes produced a 85-kDa glycosylated form. System B did not produce any detectable protein band despite the expression of a beta-galactosidase-positive control gene.

X-linked ichthyosis with hypogonadism: not always Kallmann's syndrome.

We describe two males with congenital ichthyosis secondary to steroid sulphatase deficiency who also manifested delayed puberty with biochemical features of hypogonadotrophic hypogonadism. In the first patient a history of cryptorchidism and the clinical findings of anosmia, micropenis and bimanual synkinesis suggested a contiguous gene syndrome, comprising X-linked Kallmann's syndrome and X-linked ichthyosis. An X-Y chromosomal translocation involving the Xp22.

Mirror movements in X-linked Kallmann's syndrome. II. A PET study.

To investigate the mechanism of mirror movements seen in X-linked Kallmann's syndrome, we measured changes of regional cerebral blood flow with H2 15O-PET. We studied six right-handed Kallmann male subjects and six matched, right-handed control subjects during an externally paced finger opposition task. The analyses were done both on a single subject and a group basis.

Mirror movements in X-linked Kallmann's syndrome. I. A neurophysiological study.

Possible mechanisms underlying the pathological mirror movements that are seen in the majority of patients with X-linked Kallmann's syndrome have been investigated using neurophysiological techniques. An EMG was recorded from the first dorsal interosseous muscle (1DI) during voluntary self-paced abduction of one indexed finger; EMG activity could also be recorded simultaneously from the contralateral 1DI. There was no significant difference between the time of onset of the bursts of voluntary and involuntary mirroring EMG.

Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults with Kallmann's syndrome and isolated hypogonadotropic hypogonadism and in the early midtrimester human fetus.

GnRH-secreting neurons are known to originate in the epithelium of the medial olfactory placode, whence they migrate along the axons of the terminal nerve via the forebrain and into the hypothalamus. Synaptic contact between the developing olfactory bulbs and fascicles of the vomeronasal, terminal, and olfactory nerves does not occur in Kallmann's syndrome. Consequently, there is migration arrest of GnRH cells and partial or complete failure of formation of the olfactory bulbs, resulting in severe olfactory deficit and hypogonadotropic hypogonadism.

The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis.

A detailed neurological investigation of patients with Kallmann's syndrome (KS) has been performed in an attempt to relate phenotypic characterization with genotype. Twenty-seven subjects with KS were studied (including 12 males with X-linked disease and 3 females). Six male and 2 female normosmics with isolated GnRH deficiency, 1 male with KS variant, and 1 obligate female carrier were also imaged.

Unilateral renal aplasia in X-linked Kallmann's syndrome.

Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X-linked KS, and one with X-linked KS and X-linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney.

Medical therapy for recurring catamenial pneumothorax following pleurodesis.

Background: Catamenial pneumothorax, a rare complication of systemic endometriosis, has been difficult to treat successfully. Successful medical therapy is associated with amenorrhea.

Case: A 44-year-old white woman with recurring catamenial pneumothorax underwent thoracotomy and abrasive pleurodesis.

Renal AA amyloidosis in a patient with Bence Jones proteinuria and ankylosing spondylitis.

A patient with a 10 year history of monoclonal gammopathy of undetermined significance and Bence Jones proteinuria, and a 44 year history of ankylosing spondylitis, developed a nephrotic syndrome secondary to renal amyloidosis. Clinically the amyloidosis was ascribed to Bence Jones proteinuria rather than to the burnt out ankylosing spondylitis. However, histochemical and immunofluorescence staining techniques used to type the amyloid fibrils showed AA amyloidosis, implicating ankylosing spondylitis rather than monoclonal gammopathy as the underlying cause of the patient's systemic amyloidosis and consequent nephrotic syndrome.

Right-to-left shunting after lobectomy through a patent foramen ovale.

Hypoxia and dyspnea after lung resection may be caused by a variety of factors. One entity that has been rarely described is right-to-left shunting across an interatrial communication in the absence of elevated right-sided pressures. We describe the occurrence of clinically evident right-to-left shunting after lobectomy in a patient with a patent foramen ovale and suggest that two-dimensional contrast echocardiography is a useful and minimally invasive means of diagnosing what may be a more common entity than was previously recognized.

A COMPARISON OF IMIPRAMINE, CHLORPROMAZINE AND RELATED DRUGS IN VARIOUS TESTS INVOLVING AUTONOMIC FUNCTIONS AND ANTAGONISM OF RESERPINE.

Seven structurally-related compounds consisting of three antidepressant drugs (imipramine, desmethylimipramine and amitriptyline), three tranquillizing agents (promazine, chlorpromazine and chlorprothixene) and a hybrid, desmethylpromazine, have been examined in a series of tests involving autonomic functions and antagonism of reserpine. Activities of the compounds in antagonizing reserpine-induced ptosis in rabbits and prolongation of alcohol hypnosis in mice give good correlation with their clinical actions, whilst their activities in augmenting excitation of rats by amphetamine and yohimbine toxicity in mice, and in reversing reserpine-induced bradycardia in rats offer further evidence for drug-induced sensitization to adrenergic or tryptaminic mechanisms, which is not however specific for antidepressant agents. No evidence has been obtained to indicate that a central parasympatholytic action is an important component of the antidepressant activity of imipramine and related drugs.

THE INCREASE IN THE TOXICITY OF YOHIMBINE INDUCED BY IMIPRAMINE AND OTHER DRUGS IN MICE.

In mice, yohimbine appears to accentuate the normal "alarm" reactions (alerting, flight) to external stimuli. Imipramine increases this effect and at the same time converts a non-lethal dose of yohimbine into a lethal one. The effect of imipramine is greatly reduced by adrenalectomy or by treatment with reserpine, syrosingopine, ganglion-blocking drugs or adrenaline antagonists acting on sympathetic beta-receptors.